Myles Glass has spent the past several years living life on the sidelines in a wheelchair, wishing for a better day. That day came in November 2020.

INDIANAPOLIS A 13-year-old boy living with sickle cell disease has been given a second chance at life, thanks to his mother.

Myles Glass has been through more in his young life than most adults. For the past few years, Glass has spent his days in and out of Riley Hospital for Children.

"[I] kind of have to look on the bright side of things. Being in the hospital, I meet new nurses and kids who go through what I go through. It's kind of hard to go through that at my age," Glass said.

He was diagnosed with sickle cell disease as a newborn. According to the Centers for Disease Control and Prevention, African Americans make up the largest number of people with the disease in the U.S.

Sickle cell disease is an inherited condition that impacts red blood cells and causes pain, infections and extreme fatigue. These symptoms keep Glass from doing things he loves.

"For him, it's kind of like we have to have him in a bubble," said his mother, Melissa Sanders.

Glass has spent the past several years living life on the sidelines in a wheelchair, wishing for a better day.

"[I would] hope that one day, I can do what kids do, like playing football and basketball," Glass said.

That day came in November 2020 when his mother donated bone marrow for a stem cell transplant, curing him of sickle cell disease.

"I was able to give him a second life with being a donor so that he can somewhat be a normal kid," Sanders said.

Riley Hospital for Children Dr. Seethal Jacob, who has been working with Glass and his family, said one baby every two minutes is born with sickle cell disease. She also said studies show there is a clear disparity for funding for this disease.

"There's been a lot of neglect when it comes to the disease itself. I think it's important to pay attention to the population it affects. I think that likely tells the story why sickle cell disease has been a neglected disease for so long," Jacob said.

Despite his challenges, Glass is staying positive and making strides in his physical therapy at Riley Hospital for Children.

"He's already been through harder things than most people will ever go through. I think anything else in life is going to be a piece of cake," said his physical therapist, Sarah Johnson.

"This gives me a glimpse of hope that even though you may have been diagnosed with this disease, it's not the end of the world," Sanders said.

For Glass, this is just the beginning. He hopes his story encourages other people living with sickle cell disease to keep moving forward.

"I know it's hard now, but you'll get through it. You'll be able to do what kids do your own age," Glass said.

Click here for more information on sickle cell disease and treatment options.

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Indianapolis mother gives 13-year-old son with sickle cell disease a 2nd chance at life - WTHR

Recommendation and review posted by Bethany Smith

SYDNEY, Oct. 5, 2021 /PRNewswire/ -- Clinical stage drug development company Pharmaxis Ltd (ASX: PXS) today announced further positive results of data analysis from a phase 1c clinical trial (MF-101) studying its drug PXS-5505 in patients with the bone marrow cancer myelofibrosis for 28 days at three dosage levels.

Assessment with Pharmaxis' proprietary assays of the highest dose has shown inhibition of the target enzymes, LOX and LOXL2, at greater than 90% over a 24-hour period at day 7 and day 28. The trial safety committee has reviewed the results and having identified no safety signals, has cleared the study to progress to the phase 2 dose expansion phase where 24 patients will be treated at the highest dose twice a day for 6 months.

Pharmaxis CEO Gary Phillips said, "We are very pleased to have completed the dose escalation phase of this study with such clear and positive findings.We will now immediately progress to the phase 2 dose expansion study where we aim to show PXS-5505 is safe to be taken longer term with the disease modifying effects that we have seen in the pre-clinical models. The trial infrastructure and funding is in place and we are on track to complete the study by the end of 2022."

Independent, peer-reviewed research has demonstrated the upregulation of several lysyl oxidase family members in myelofibrosis.The level of inhibition of LOX achieved in the current study at all three doses significantly exceeds levels that caused disease modifying effects with PXS-5505 in pre-clinical models of myelofibrosis with improvements in blood cell count, diminished spleen size and reduced bone marrow fibrosis. LOXL2 was inhibited to a similar degree and based on pre-clinical work such high inhibition is likely replicated for other LOX family members (LOXL1, 3 and 4).[1] Study data can be viewed in the full announcement.

Commenting on the results of the trial, Dr Gabriela Hobbs, Assistant Professor, Medicine, Harvard Medical School & Clinical Director, Leukaemia, Massachusetts General Hospital said, "Despite improvements in the treatment of myelofibrosis, the only curative therapy remains an allogeneic stem cell transplantation, a therapy that many patients are not eligible for due to its morbidity and mortality. None of the drugs approved to date consistently or meaningfully alter the fibrosis that defines this disease. PXS-5505 has a novel mechanism of action by fully inhibiting all LOX enzymes. An attractive aspect of this drug is that so far in healthy controls and in this phase 1c study in myelofibrosis patients, the drug appears to be very well tolerated. This is meaningful as approved drugs and those that are undergoing study, are associated with abnormal low blood cell counts. Preliminary data thus far, demonstrate that PXS-5505 leads to a dramatic, >90% inhibition of LOX and LOXL2 at one week and 28 days. This confirms what's been shown in healthy controls as well as mouse models, that this drug can inhibit the LOX enzymes in patients. Inhibiting these enzymes is a novel approach to the treatment of myelofibrosis by preventing the deposition of fibrosis and ultimately reversing the fibrosis that characterizes this disease."

The phase 1c/2a trial MF-101 cleared by the FDA under the Investigational New Drug (IND) scheme aims to demonstrate that PXS-5505, the lead asset in Pharmaxis' drug discovery pipeline, is safe and effective as a monotherapy in myelofibrosis patients who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs. Trial sites will now open to recruit myelofibrosis patients into the 6-month phase 2 study in Australia, South Korea, Taiwan and the USA.

An effective pan-LOX inhibitor for myelofibrosis would open a market that is conservatively estimated at US$1 billion per annum.

While Pharmaxis' primary focus is the development of PXS-5505 for myelofibrosis, the drug also has potential in several other cancers including liver and pancreatic cancer where it aims to breakdown the fibrotic tissue in the tumour and enhance the effect of chemotherapy treatment.

Trial Design

Name of trial

PXS5505-MF-101: A phase 1/2a study to evaluate safety, pharmacokinetic and pharmacodynamic dose escalation and expansion study of PXS-5505 in patients with primary, post-polycythaemia vera or post-essential thrombocythemia myelofibrosis

Trial number

NCT04676529

Primary endpoint

To determine the safety of PXS-5505 in patients with myelofibrosis

Secondary endpoints

Blinding status

Open label

Placebo controlled

No

Trial design

Randomised, multicentre, 4 week duration phase 1 (dose escalation) followed by 6 month phase 2 (dose expansion)

Treatment route

Oral

Treatment frequency

Twice daily

Dose level

Dose escalation: three escalating doses

Dose expansion: one dose

Number of subjects

Dose escalation: minimum of three patients to maximum of 18 patients

Dose expansion: 24 patients

Subject selection criteria

Patients with primary or secondary myelofibrosis who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs

Trial locations

Dose escalation: Australia (2 sites) and South Korea (4 sites)

Dose expansion: Australia, Korea, Taiwan, USA

Commercial partners involved

No commercial partner

Reference: (1) doi.org/10.1002/ajh.23409

AUTHORISED FOR RELEASE TO ASX BY:

Pharmaxis Ltd Disclosure Committee. Contact: David McGarvey, Chief Financial Officer and Company Secretary: T +61 2 9454 7203, E [emailprotected]

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About Pharmaxis

Pharmaxis Ltd is an Australian clinical stage drug development company developing drugs for inflammatory and fibrotic diseases, with a focus on myelofibrosis. The company has a highly productive drug discovery engine built on its expertise in the chemistry of amine oxidase inhibitors, with drug candidates in clinical trials. Pharmaxis has also developed two respiratory products which are approved and supplied in global markets, generating ongoing revenue.

Pharmaxis is developing its drug PXS-5505 for the bone marrow cancer myelofibrosis which causes a build up of scar tissue that leads to loss of production of red and white blood cells and platelets. The US Food and Drug Administration has granted Orphan Drug Designation to PXS-5055 for the treatment of myelofibrosis and permission under an Investigational Drug Application (IND) to progress a phase 1c/2 clinical trial that began recruitment in Q1 2021. PXS5505 is also being investigated as a potential treatment for other cancers such as liver and pancreatic cancer.

Other drug candidates being developed from Pharmaxis' amine oxidase chemistry platform are targeting fibrotic diseases such as kidney fibrosis, NASH, pulmonary fibrosis and cardiac fibrosis; fibrotic scarring from burns and other trauma; and inflammatory diseases such as Duchenne Muscular Dystrophy.

Pharmaxis has developed two products from its proprietary spray drying technology that are manufactured and exported from its Sydney facility; Bronchitol for cystic fibrosis, which is approved and marketed in the United States, Europe, Russia and Australia; and Aridol for the assessment of asthma, which is approved and marketed in the United States, Europe, Australia and Asia.

Pharmaxis is listed on the Australian Securities Exchange (PXS). Its head office, manufacturing and research facilities are in Sydney, Australia. http://www.pharmaxis.com.au

About PXS-5505

PXS-5505 is an orally taken drug that inhibits the lysyl oxidase family of enzymes, two members LOX and LOXL2 are strongly upregulated in human myelofibrosis. In pre-clinical models of myelofibrosis PXS-5505 reversed the bone marrow fibrosis that drives morbidity and mortality in myelofibrosis and reduced many of the abnormalities associated with this disease. It has already received IND approval and Orphan Drug Designation from the FDA.

About Myelofibrosis

Myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure. Under normal conditions, the bone marrow provides a fine network of fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres.

In myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over-stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow for example in the spleen and liver, which become enlarged as a result.

Myelofibrosis can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of myelofibrosis remains largely unknown. It can be classified as either JAK2 mutation positive (having the JAK2 mutation) or negative (not having the JAK2 mutation).

Source: Australian Leukemia Foundation: https://www.leukaemia.org.au/disease-information/myeloproliferative-disorders/types-of-mpn/primary-myelofibrosis/

Forward-looking statements

Forwardlooking statements in this media release include statements regarding our expectations, beliefs, hopes, goals, intentions, initiatives or strategies, including statements regarding the potential of products and drug candidates. All forward-looking statements included in this media release are based upon information available to us as of the date hereof. Actual results, performance or achievements could be significantly different from those expressed in, or implied by, these forward-looking statements. These forward-looking statements are not guarantees or predictions of future results, levels of performance, and involve known and unknown risks, uncertainties and other factors, many of which are beyond our control, and which may cause actual results to differ materially from those expressed in the statements contained in this document. For example, despite our efforts there is no certainty that we will be successful in developing or partnering any of the products in our pipeline on commercially acceptable terms, in a timely fashion or at all. Except as required by law we undertake no obligation to update these forward-looking statements as a result of new information, future events or otherwise.

CONTACT:

Media: Felicity Moffatt: T +61 418 677 701, E [emailprotected]

Investor relations:Rudi Michelson (Monsoon Communications) T +61 411 402 737, E [emailprotected]

SOURCE Pharmaxis Limited

http://www.pharmaxis.com.au

Read more:
Pharmaxis Cleared To Progress To Phase 2 Bone Marrow Cancer Trial - PRNewswire

Recommendation and review posted by Bethany Smith

TUCSON, Ariz., Oct. 5, 2021 /PRNewswire/ --On November 15th, 2021, healthcare professionals and the general public are invited to participate in World Cord Blood Day 2021 (www.WorldCordBloodDay.org) via a free online conference and live educational events being held around the globe. Registration is now open (free, public welcome).

Cord blood is the blood left in the umbilical cord and placenta following the birth of a child. It is rich in life-saving stem cells. While cord blood has been used for over 30 years, Covid-19 has renewed interest in this medical resource given its unique regenerative qualities and the fact that most cord blood currently stored was collected prior to the pandemic. These units are naturally Covid-free, an advantage over many other stem cell sources. Yet, cord blood is still thrown away as medical waste in the majority of births worldwide. Education is key to changing this practice and World Cord Blood Day 2021 will provide the perfect opportunity for OBGYNs, midwives, transplant doctors, nurses, parents and students to learn about this vital medical resource.

During World Cord Blood Day 2021, participants will learn how cord blood is used to treat over 80 life-threatening diseases such as leukemia and lymphoma, bone marrow failure, immune deficiency diseases and inherited blood disorders such as thalassemia and sickle cell disease. Leading transplant doctors and researchers will also highlight cord blood's role in the emerging fields of gene therapy and regenerative medicine to potentially treat cerebral palsy, autism, stroke and more.

Organized by Save the Cord Foundation, a 501c3 non-profit, World Cord Blood Day 2021 is officially sponsored by QuickSTAT Global Life Science Logistics, recognized leader in medical shipping and healthcare logistics. Inspiring Partners include Be the Match (NMDP), World Marrow Donor Association (WMDA-Netcord), AABB Center for Cellular Therapies, Cord Blood Association, and the Foundation for the Accreditation of Cellular Therapy (FACT).

"QuickSTAT, part of Kuehne+Nagel, is proud to sponsor the 5th annual World Cord Blood Day to help support and educate the healthcare community and expectant parents about the life-saving value of cord blood stem cells. We're excited to play a role in the research and development of cord blood derivative therapies by providing logistics supply chain solutions to cord blood, biotech and pharmaceutical companies worldwide," said Monroe Burgess, VP Life Science Commercial Marketing, QuickSTAT.

Visit http://www.WorldCordBloodDay.org to learn how you can participate. Show your support on social media: @CordBloodDay, #WorldCordBloodDay, #WCBD21

About Save the Cord FoundationSave the Cord Foundation (a 501c3 non-profit) was established to advance cord blood education providing non-commercial information to health professionals and the public regarding methods for saving cord blood, as well as current applications and the latest research. http://www.SaveTheCordFoundation.org.

About QuickSTAT Global Life Science LogisticsEvery day, QuickSTAT, a part of Kuehne+Nagel, safely and reliably moves thousands of critical shipments around the world. For over forty years, QuickSTAT has been entrusted with transporting human organs and tissue for transplant or research, blood, blood products, cord blood, bone marrow, medical devices, and personalized medicine, 24/7/365. QuickSTAT's specially trained experts work with hospitals, laboratories, blood banks and medical processing centers, and utilize the safest routes to ensure integrity, temperature control and chain of custody throughout the transportation process. Learn more at http://www.quickstat.aero.

Contact:Charis Ober(520) 419-0269[emailprotected]

SOURCE Save the Cord Foundation

http://www.SaveTheCordFoundation.org

Link:
Ready to Treat Over 80 Life-Threatening Diseases, Discover the Potential of Cord Blood during World Cord Blood Day 2021 - PRNewswire

Recommendation and review posted by Bethany Smith

A student has completed the London Marathon alongside the stem cell donor who saved her life.

icky Lawrence, 21, from Moseley, Birmingham, was diagnosed with severe aplastic anaemia in 2008, when she was eight years old, a condition in which the bone marrow does not produce an adequate number of new blood cells.

Thanks to Elliott Brock, a physiotherapist from Mersea Island, Essex, Ms Lawrence received a transplant that same year.

Ms Lawrence sent Mr Brock a letter in 2015 and the pair met for the first time.

Fast forward to 2021 and they have just completed the London Marathon in support of Anthony Nolan.

Ms Lawrence, who is in her fourth year of a medical degree at Newcastle University, told the PA news agency that completing the marathon was absolutely amazing.

She said: Crossing the finish line was so emotional, not just because wed run 26 miles, but running 26 miles alongside the man who saved your life is a pretty big feat.

Ms Lawrence added: A big slogan of Anthony Nolan is without your support, there is no cure.

Without Elliott donating his stem cells to a stranger, I would not be here. I wouldnt have made it to Christmas. I would never have had the opportunities Ive had to go to university, to study abroad, to play hockey.

Him donating his stem cells gave me a second life and there are still so many people that need a transplant that are not finding the matches they need, especially among the ethnic minority community.

Unfortunately if you are of ethnic minority background, you only have a 37% chance of finding a match.

Mr Brock, 42, who wore a mask and cape during the race, said: That was a tongue of check nod [to the fact that the] easiest way to be called a hero is to donate your bone marrow.

I cannot emphasise to people enough that it is pain-free.

He added: It was just a day of celebration for London to celebrate having their marathon back.

The crowds were amazing and obviously to be side-by-side with the girl whose life, through the amazing work of Anthony Nolan, I managed to save sort of 13 years ago was just surreal really.

Its a lovely story of how my simple act made such a massive difference and we are able to celebrate it so many years after.

Anthony Nolan chief executive Henny Braund said: We are so grateful to Vicky and Elliott for running to raise funds and awareness of Anthony Nolan and the lifesaving work that we do.

Every day five Vickys, patients with blood cancer or a blood disorder, start their search for an Elliott.

If youre aged 16-30 and in good health, please consider joining the Anthony Nolan stem cell register. You could potentially save a life.

More information on how to join the stem cell register can be found at: http://www.anthonynolan.org/help-save-a-life/join-stem-cell-register

Originally posted here:
Student completes London Marathon with the man who saved her life - Independent.ie

Recommendation and review posted by Bethany Smith

StemExpress to use utilize the Thermo Fisher Accula rapid PCR testing system to provide event attendees with accurate results in 30 minutes.

Published: Oct. 5, 2021 at 2:33 PM CDT|Updated: 3 hours ago

SACRAMENTO, Calif., Oct. 5, 2021 /PRNewswire/ --StemExpress is proud to announce that they will be the official COVID-19 testing provider for 2021's Meeting on the Mesa, a hybrid event bringing together great minds in the cell and gene biotech sphere. It has partnered with Alliance for Regenerative Medicine to comply with the newly implemented California state COVID-19 vaccination and testing policy regarding gatherings with 1,000 or more attendees. This partnership will allow the vital in-person networking aspect of the event to commence while protecting the health and safety of participants and attendees.

In-person networking commences at the 2021 Cell and Gene Meeting on the Mesa with COVID-19 testing options provided by StemExpress.

As a leading global provider of human biospecimen products, StemExpress understands the incredible impact that Meeting on the Mesa has on the industry and has been a proud participant for many years. For over a decade, StemExpress has provided the cell and gene industry with vital research products and holds valued partnerships with many of this year's participants. As such, it understands the immense value that in-person networking provides and is excited to help bring this element back to the meeting safely and responsibly.

StemExpress has been a trusted provider of widescale COVID-19 testing solutions since early 2020 - providing testing for government agencies, public health departments, private sector organizations, and the public nationwide. For Meeting on the Mesa, StemExpress is offering convenient testing options for unvaccinated attendees and those traveling from outside of the country. Options will include take-home RT-PCR COVID Self-Testing Kits and on-site, rapid PCR testing for the duration of the event. The self-testing kit option allows attendees to test for COVID in the days leading up to the event for a seamless admission and the days following the event to confirm they haven't been exposed. The on-site rapid testing option utilizes the new Thermo Fisher Accula, offering in-person testing at the event with results in around 30 minutes. StemExpress is excited to bring these state-of-the-art COVID testing solutions to the frontlines of the Cell & Gene industry to allow for safe in-person connections.

The StemExpress partnership with Alliance for Regenerative Medicine seeks to empower the entire cell and gene industry with a long-awaited opportunity to return to traditional networking practices. It is well known that innovation doesn't exist in a vacuum - allowing great minds to come together is a sure way to spur scientific growth and advance cutting-edge research, giving hope for future cures.

Cell and Gene Meeting on the Mesa will take place October 12th, 2021, through October 14th, 2021, at Park Hyatt Aviara,7100 Aviara Resort Drive Carlsbad, CA 92011. To learn more about the event, please visit MeetingOnTheMesa.com.

For more information about COVID testing solutions for businesses and events, visit https://www.stemexpress.com/covid-19-testing/.

About StemExpress:

Founded in 2010 and headquartered in Sacramento, California, StemExpress is a leading global biospecimen provider of human primary cells, stem cells, bone marrow, cord blood, peripheral blood, and disease-state products. Its products are used for research and development, clinical trials, and commercial production of cell and gene therapies by academic, biotech, diagnostic, pharmaceutical, and contract research organizations (CRO's).

StemExpress has over a dozen global distribution partners and seven (7) brick-and-mortar cellular clinics in the United States, outfitted with GMP certified laboratories. StemExpress runs its own non-profit supporting STEM initiatives, college and high school internships, and women-led organizations. It is registered with the U.S. Food and Drug Administration (FDA) and is continuously expanding its network of healthcare partnerships, which currently includes over 50 hospitals in Europe and 3 US healthcare systems - encompassing 31 hospitals, 35 outpatient facilities, and over 200 individual practices and clinics.

StemExpress has been ranked by Inc. 500 as one of the fastest-growing companies in the U.S.

About the Alliance for Regenerative Medicine:

The Alliance for Regenerative Medicine (ARM) is the leading international advocacy organization dedicated to realizing the promise of regenerative medicines and advanced therapies. ARM promotes legislative, regulatory, reimbursement and manufacturing initiatives to advance this innovative and transformative sector, which includes cell therapies, gene therapies and tissue-based therapies. Early products to market have demonstrated profound, durable and potentially curative benefits that are already helping thousands of patients worldwide, many of whom have no other viable treatment options. Hundreds of additional product candidates contribute to a robust pipeline of potentially life-changing regenerative medicines and advanced therapies. In its 12-year history, ARM has become the voice of the sector, representing the interests of 400+ members worldwide, including small and large companies, academic research institutions, major medical centers and patient groups. To learn more about ARM or to become a member, visit http://www.alliancerm.org.

Media Contact: Anthony Tucker, atucker@stemexpress.com

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SOURCE StemExpress

The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

Link:
StemExpress Partners with the Alliance for Regenerative Medicine to Provide COVID-19 Testing for the Cell and Gene Meeting on the Mesa - WSAW

Recommendation and review posted by Bethany Smith

Published: Oct. 4, 2021 at 6:00 AM EDT

NEW YORK, Oct. 4, 2021 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today that Stacy Lindborg, Ph.D., Executive Vice President and Head of Global Clinical Research, will deliver a presentation at the2021 Cell & Gene Meeting on the Mesa, being held as a hybrid conferenceOctober 12-14, and October 19-20, 2021.

Dr. Lindborg's presentation highlights the expansion of Brainstorm's technology portfolio to include autologous and allogeneic product candidates, covering multiple neurological diseases. The most progressed clinical development program, which includes a completed phase 3 trial of NurOwn in ALS patients, remains the highest priority for Brainstorm. Brainstorm is committed to pursuing the best and most expeditious path forward to enable patients to access NurOwn.

Dr. Lindborg's presentation will be in the form of an on-demand webinar that will be available beginning October 12. Those who wish to listen to the presentation are required to registerhere. At the conclusion of the 2021 Cell & Gene Meeting on the Mesa, a copy of the presentation will also be available in the "Investors and Media" section of the BrainStorm website underEvents and Presentations.

About the 2021 Cell & Gene Meeting on the Mesa

The meeting will feature sessions and workshops covering a mix of commercialization topics related to the cell and gene therapy sector including the latest updates on market access and reimbursement schemes, international regulation harmonization, manufacturing and CMC challenges, investment opportunities for the sector, among others. There will be over 135 presentations by leading public and private companies, highlighting technical and clinical achievements over the past 12 months in the areas of cell therapy, gene therapy, gene editing, tissue engineering and broader regenerative medicine technologies.

The conference will be delivered in a hybrid format to allow for an in-person experience as well as a virtual participation option. The in-person conference will take place October 12-14 in Carlsbad, CA. Virtual registrants will have access to all content via livestream during program dates. Additionally, all content will be available on-demand within 24 hours of the live program time. Virtual partnering meetings will take place October 19-20 via Zoom.

About NurOwn

The NurOwntechnology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwntechnology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 pivotal trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive multiple sclerosis (MS) and was supported by a grant from the National MS Society (NMSS).

For more information, visit the company's website atwww.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future NurOwnmanufacturing and clinical development plans, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may," "should," "would," "could," "will," "expect,""likely," "believe," "plan," "estimate," "predict," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, the prospects for regulatory approval of BrainStorm's NurOwntreatment candidate, the initiation, completion, and success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwntreatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture, or to use third parties to manufacture, and commercialize the NurOwntreatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

ContactsInvestor Relations:Eric GoldsteinLifeSci Advisors, LLCPhone: +1 646.791.9729egoldstein@lifesciadvisors.com

Media:Paul TyahlaSmithSolvePhone: + 1.973.713.3768Paul.tyahla@smithsolve.com

Logo- https://mma.prnewswire.com/media/1166536/BrainStorm_Logo.jpg

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SOURCE Brainstorm Cell Therapeutics Inc

The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

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BrainStorm to Present at the 2021 Cell & Gene Meeting on the Mesa - WWNY

Recommendation and review posted by Bethany Smith

A genetic syndrome that affects bones

Osteogenesis Imperfecta (OI) is a hereditary disorder occurring in 1:10,000 births and characterised by osteopenia (bone loss) and skeletal fragility (fractures). Secondary features include short stature, skeletal deformities, blue sclera and dentinogenesis imperfect. (1) There is a large clinical variability in OI, and severity ranges from mild to lethal, based on radiological characteristics. Genetically, OI is a collagen-related syndrome. Type I collagen is a heterotrimeric helical structure synthesized by bone-forming cells (osteoblasts), and it constitutes the most abundant protein of the skeletal organic matrix. (2) Synthesis of type I collagen is a complex process. (3) Collagen molecules are cross-linked into fibrils (which confer tensile strength to the bones). Those are then mineralised by hydroxy-apatites (which provides compressive strength) and assembled into fibres.

Dominant mutations in either the COL1A1 or the COLA1A2 genes are responsible for up to 90% of all OI cases. These mutations (more than 1,000 of which have been identified) lead to impairment of collagen structure and production, which in either quantitative or qualitative bone extracellular matrix (ECM) defects. Mutations affecting ECM structure have serious health consequences because the skeleton protects visceral organs and the central nervous system and provides structural support. Bones also store fat in the yellow bone marrow found within the medullary cavity, whilst the red marrow located at the end of long bones is the site of haematopoiesis. In addition, the ECM constitutes a reservoir of phosphate, calcium, and growth factors, and is involved in trapping dangerous molecules.

Stem cell therapy for OI aims to improve bone quality by harnessing the ability of mesenchymal stem cells (MSC) to differentiate into osteoblasts, with the rationale that donor cells would engraft into bones, produce normal collagen and function as a cell replacement. Stem cells have, therefore, been proposed for the treatment of OI (4) and, in particular, prenatal foetal stem cell therapy (foetal stem cells injected into a foetus, i.e. foetal-to-foetal) approach, which offers a promising route to effective treatment. (5) Human foetal stem cells are more primitive than stem cells isolated from adult tissues and present advantageous characteristics compared to their adult counterparts, i.e. they possess a higher level of plasticity, differentiate more readily into specific lineages, grow faster, senesce later, express higher levels of adhesion molecules, and are smaller in size. (6,7) Prenatal cell therapy capitalises on the small size of the foetus and its immunological naivete. In addition, stem cells delivered in utero benefit from the expansion of endogenous stem cells and may prevent organ injury before irreversible damage. (8)

However, human foetal stem cells used are isolated from either foetal blood drawn by cardiac puncture, either during termination of pregnancy or during ongoing pregnancy, albeit using an invasive procedure associated with a high risk of morbidity and mortality for both the foetus and the mother (9). Foetal cells can also be isolated from the first-trimester liver (following termination of pregnancy) and such cells are currently used in The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial, which aims to investigate the safety and efficacy of transplanting foetal derived MSCs prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI) (10). Alternatively, foetal stem cells can be isolated during ongoing pregnancy from the amniotic fluid, either during mid-trimester amniocentesis or at birth (11,12) or from the chorionic villi of the placenta during first-trimester chorionic villi sampling (13).

We have demonstrated that human fetal stem cells isolated from first trimester blood possess superior osteogenic differentiation potential compared to adult stem cells isolated from bone marrow and to fetal stem cells isolated from first trimester liver. We showed that in utero transplantation of these cells in an experimental model of severe OI resulted in a drastic 75% decrease in fracture rate incidence and skeletal brittleness, and improvement of bone strength and quality.(14) A similar outcome was obtained using placenta-derived foetal stem cells (15) and amniotic fluid stem cells following perinatal transplantation into experimental models. (16,17)

Understanding the mechanisms of action of donor cells will enable the engineering of donor cells with superior efficacy to stimulate bone formation and strengthen the skeleton. Despite their potential to differentiate down the osteogenic lineage, there is little evidence that donor cells contribute to regenerating bones through direct differentiation, due to the very low level of donor cell engraftment reported in all our studies. When placed in an osteogenic microenvironment in vitro, foetal stem cells readily differentiate into osteoblasts and produce wild type collagen molecules. However, there are insufficient proofs that collagen molecules of donor cell origin contribute to the formation of the host bone ECM to confer superior resistance to fracture.

It is now well accepted that stem cells can influence the behaviour of target cells through the release of paracrine factors and, therefore, contribute to tissue regeneration indirectly. We have indeed recently shown that donor stem cells stimulate the differentiation of resident osteoblasts, which were unable to fully mature in the absence of stem cell treatment. (16,17) We are now focusing our efforts on understanding the precise molecular mechanisms by which donor cells improve skeletal health to counteract bone fragility caused by various OI-causative mutations.

References

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Introduction

The growing burden of ischemic heart disease (IHD) is a major public health issue. The most harmful type of IHD is acute myocardial infarction (MI), which leads to loss of tissue and impaired cardiac performance, accounting for two in five deaths in China.1 Timely revascularization after MI, including percutaneous coronary intervention, thrombolytic treatment and bypass surgery, is key to improving cardiac function and preventing post-infarction pathophysiological remodeling.2 However, these effective but invasive approaches cannot be used in all patients owing to their applicability, which is limited based on specific clinical characteristics, and the possibility of severe complications such as bleeding and reperfusion injury.2,3 Attempts to limit infarct size and improve prognosis using pharmacotherapy (including antiplatelet and antiarrhythmic drugs and angiotensin-converting enzyme inhibitors) without reperfusion has been proven generally inefficient, due to non-targeted drug distribution and side effects, and short half-life of some drugs.1,3,4 Consequently, many patients in which this approach is used still progress to cardiac hypertrophy and heart failure.1 Growth and rupture of atherosclerotic plaques and the ensuing thrombosis are the major causes of acute MI.4 Currently available interventions for atherosclerosis (AS) including statins can reduce acute MI, but the effects vary between individuals, and leave significant residual risks.58 Some chemotherapies, such as docetaxel9 and methotrexate,10,11 also seem to have beneficial effects in AS; however, systemic administration of these drugs is limited because of their adverse effects.12 The demand for safer and more efficient therapies and prevention strategies for MI is therefore increasing.

Several optimized strategies have so far been explored, one of which is the application of nanoparticles (NPs). These nanoscale particles have been widely used in the treatment of tumors and neural diseases.13,14 NPs enable delivery of therapeutic compounds to target sites with high spatial and temporal resolution, enhancement of tissue engineering processes and regulation of the behaviour of transplants such as stem cells. The application of NPs improves the therapeutic effects and minimizes the adverse effects of traditional or novel therapies, increasing the likelihood that they can be successfully translated to clinical settings.1518 However, research on NPs in this field is still in its infancy.5,1921 This review summarizes the latest NP-based strategies for managing acute MI, mostly published within the past 7 years, with a particular focus on effects and mechanisms rather than particle types, which have been extensively covered in other reviews (Figure 1). In addition, we offer an initial viewpoint on the value of function-based systems over those based on materials, and discuss future prospects in this field.

Figure 1 Overview of nanoparticle-based strategies for the treatment and prevention of myocardial infarction. Nanoparticles are capable of delivering therapeutic agents and nucleic acids in a stable and targeted manner, improving the properties of tissue engineering scaffolds, labeling transplanted cells and regulating cell behaviors, thus promoting the cardioprotective effects of traditional or novel therapies.

A multitude of NP types are currently under investigation, including lipid-based NPs, polymeric NPs, micelles, inorganic NPs, and exosomes. Virus can also be considered as NPs; however they will not be discussed in this review.22 NPs made from different materials show similar in vivo metabolic kinetic characteristics and protective effects on infarcted heart.19,20 Function-based NP types, oriented towards a specific purpose, may be preferable compared with traditional types, on account of their practicality in basic research and clinical translation. In this review, we discuss NPs used in the treatment and prevention of MI that fall into the following four categories: 1) circulation-stable nanocarriers (polymeric, lipid or inorganic particles); 2) targeted delivery vectors (magnetic or particles modified to improve target specificity); 3) enhancers of tissue engineering; and 4) regulators of cell behavior (Figure 1). We propose that the choice of each NP for any given application should be primarily based on the roles or mechanisms they perform.

Many NPs, whether composed of either naturally occurring or synthetic materials, act as nanocarriers to improve the circulating stability of therapeutic agents.15,16 Polymeric NPs comprise one of the most widely employed types, with excellent biocompatibility, tunable mechanical properties, and the ability be easily modified with therapeutic agents using a broad range of chemical techniques.23,24 The most commonly used polymer for these NPs is polylactide-co-glycolide (PLGA), which has Food and Drug Administration approval.25,26 Recently, there has been a therapeutic emphasis on polydopamine (PDA), from which several related nanomaterials have been created, including PDA NPs and PDA NP-knotted hydrogels.27,28 NPs made from polylactic acid (PLA),29,30 poly--caprolactone (PCL),31 polyoxalates,32 polyacrylonitrile,33 chitosan29,34 and hollow mesoporous organosilica35 have also been constructed and administered in vitro in cells and in vivo in animal models.

Lipid NPs or liposomes are also considered promising candidates for the delivery of therapeutic agents, due to their morphology, which is similar to that of cellular membranes and ability to carry both lipophilic and hydrophilic drugs. These non-toxic, non-immunogenic and biodegradable amphipathic nanocarriers can be designed to reduce capture by reticuloendothelial cells, increase circulation time, and achieve satisfactory targeting.36,37 Solid lipid NPs (SLNs) combine the advantages of polymeric NPs, fat emulsions, and liposomes, remaining in a solid state at room temperature. Active key components of SLNs are mainly physiological lipids, dispersed in aqueous solution containing a stabilizer (surfactant).38 Micelles are made by colloidal aggregation in a solution through self-assembly of amphiphilic polymers, or a simple lipidic layer of transfer vehicles;39 these have been used in cellular and molecular imaging40 and treatment41 for a long time.

Inorganic NPs used in basic IHD research are classified as metal, metal compounds, carbon,42 or silicon NPs;43 these are relatively inert, stable, and biocompatible. Gold (Au),44 silver (Ag)45 and copper (Cu)46 are commonly used materials in their production. These NPs can be delivered orally,47 or injected intravenously48 or intraperitoneally.56 However, they are more widely used to construct electrically conductive myocardial scaffolds in tissue engineering.49,50 Myocardial patches and scaffolds are promising therapeutic approaches to repairing heart tissue after IHD; incorporating conductive NPs can further improve functionality, introducing beneficial physical properties and electroconductivity. Some organic particles, such as liposomes anchored with poly(N-isopropylacrylamide)-based copolymer groups, are also suitable for the production of effective nanogels or patches for this purpose.37

Several metal compounds have been used for treatment of IHD.5154 The application of magnetic particles made from iron oxide has been of particular interest in recent research. These NPs are more prone to manipulation with an external magnetic field, and thus serve as powerful tools for targeted delivery of therapeutics. In addition, modification with targeted peptides or antibodies is another approach to the construction of targeted delivery systems.

Another strategy to protect cardiac performance after MI is the transplantation of cells; however, the beneficial effects of this are currently limited.58 Many NPs can improve the behavior of cells; in this context, they may stimulate cardioprotective potential. In particular, exosomes a major subgroup of extracellular vesicles (EVs) with a diameter of 30150nm, which are secreted via exocytosis55 represent novel, heterogeneous, biological NPs with an endogenous origin. They are able to carry a variety of proteins, lipids, nucleic acids, and other bioactive substances.5557 Mechanistic studies have confirmed that exosomes offer a cell-free strategy to rescue ischemic cardiomyocytes (CMs).59,60

The physical properties of NPs, including size, shape, and surface charge, impact on how biological processes behave, and consequently, responses in the body.61 The recommended definition of NPs in pharmaceutical technology and biomedicine includes a limitation that more than 50% of particles should be in a size distribution range of 10100 nm.39 However, this is not strictly distinguished in studies, so for the purposes of this review, we have relaxed this definition. Small NPs have a faster uptake and processing speed and longer blood circulation half-lives than larger ones; a decreased surface area results in increased reactivity to the microenvironment and greater speed of release of the compounds they carry.6163 However, an exception to this principle is that, among particles of less than 50 nm diameter, larger NPs have longer circulatory half-lives.64,65 NPs can be spherical, discoidal, tubular or dendritic.61,63 The impact of NP shape on uptake and clearance has also been revealed;66,67 for instance, spheres endocytose more easily,20 while micelles and filomicelles target aortic macrophages, B cells, and natural killer (NK) cells in the immune system more effectively than polymersomes.68 In terms of charge, cationic NPs are more likely to interact with cells than negatively charged or neutral particles because the mammalian cell membrane is negatively charged.62 As a result, positively charged particles are reported to be more likely to destabilize blood cell membranes and cause cell lysis.61 Additionally, the rate of drug release is largely determined by the diameter of the pore. Motivated by the idea, Palma-Chavez et al developed a multistage delivery system by encapsulating PLGA NPs in micron-sized PLGA outer shells.69

Some types of NPs, such as micelles, possess coreshell morphological structures: a core composed of hydrophobic block segments is surrounded by hydrophilic polymer blocks in a shell that stabilizes the entire micelle. The core provides enough space to accommodate compounds, while the shell protects drug molecules from hydrolysis and enzymatic degradation.36 Surface chemical composition largely governs the chemical interactions between NPs and molecules in the body. Appropriate surface coatings can create a defensive layer, protect encapsulated cargo, and affect biological behaviors. Coating with inert polymers like polyethylene glycol (PEG) is the most commonly used method, which hinders interactions with proteins, alters the composition of the protein corona, attenuate NP recognition by opsonins which tag particles for phagocytosis, and extend the half-life of particles.36,70 Additionally, PEG coating helps the therapeutic agents reach ischemic sites, because PEGylated macromolecules tend to diffuse in the interstitial space of the heart.71 Functionalization of gangliosides can further attenuate the immunogenicity of PEGylated liposomes without damaging therapeutic efficacy.72 Removal of detachable PEG conjugates in the microenvironment of the target sites improves capture by cells. Wang and colleagues synthesized PDA-coated tanshinone IIA NPs by spontaneous hydrophobic self-assembly.73 Polyethyleneimine (PEI) is capable of condensing nucleic acid and overcoming hamper of cell membrane. Therefore, modification with PEI is mainly used for the transport of DNA and RNA.74 Of note, despite their inertness, novel NPs composed of metals can also be modified with compounds such as PEG, thiols, and disulfides.48,75 Hydrogels mixed with peptide-coated Au NPs attain greater viscosity than hydrogels mixed with Au NPs.24

Targeted delivery is a primary goal in the development of nanocarriers. Passive targeting is based on enhanced permeability in ischemic heart tissue, which does not meet the needs of clinical application.76 This fact has prompted work on targeting agent modification and magnetic guidance. Conjugation with specific monoclonal antibodies is a feasible method for delivering drug payloads targeted to ischemic lesions. Copper sulfide (CuS) NPs coupled to antibodies targeting transient receptor potential vanilloid subfamily 1 (TRPV1), permit specific binding to vascular smooth muscle cells (SMCs), and can also act as a switch for photothermal activation of TRPV1 signaling.52 In another study conducted by Liu and colleagues, two types of antibodies, binding CD63 (expressed on the surface of exosomes) or myosin light chain (MLC, expressed on injured CMs) are utilized to allow NPs to capture exosomes and accumulate in ischemic heart tissue. These NPs have a unique structure comprising an ferroferric oxide core and PEG-decorated silica shell, which simultaneously enables magnetic manipulation and molecule conjugation via hydrazone bonds.21 Targeted peptides such as atrial natriuretic peptide (ANP),43 S2P peptide (plague-targeting peptide),77 and stearyl mannose (type 2 macrophage-targeting ligand)16 allow NPs to precisely target atherosclerotic tissue and ischemic heart lesions. Modification with EMMPRIN-binding peptide (AP9) has been shown to enable more rapid uptake of micelles by H9C2 myoblasts and primary CMs and to deliver drug payloads targeted to lesions in vivo.78,79 Another strategy for targeted nanocarriers is to produce cell mimetic carriers. Using the inflammatory response as a marker after MI,76 Boada and colleagues synthesized biomimetic NPs (leukosomes) by integrating membrane proteins purified from activated J774 macrophages into the phospholipid bilayer of NPs. Local chronic inflammatory lesions demonstrated overexpression of adhesion molecules, which bound leukosomes efficiently.80

The biocompatibility of NPs is difficult to predict because any interaction with molecules or cells can cause toxic effects. Generally, NPs remain in blood, but can also extravasate from vasculature with enhanced permeability, or accumulate in the mononuclear phagocyte system.81 Important causes of NP-associated toxicity include: oxidative stress injury and cell apoptosis secondary to the production of free radicals, lack of anti-oxidants, phagocytic cell responses, and the composition of some types of particles.61 Hepatotoxicity, nephrotoxicity and any other potential off-target organ damage caused by accumulation of particles, especially those with poor degradability and slow clearance, are also essential to explore in toxicity tests.82 Additionally, the evaluation of evoked immune responses according to the expression of inflammatory factors and stimulation of leukocytes in cell lines and animal models is also important.83

A few studies have reported NP-associated acute and chronic hazards in pharmacological applications, although some of these observations may be contentious. Specifically, aggregation of non-functionalized carbon nanotubes (CNTs) has been observed owing to inherent hydrophobicity of these particles.61 Aside from inflammation and T lymphocyte apoptosis, multi-walled CNTs can rupture cell membranes, resulting in macrophage cytotoxic effects.84,85 Silica NPs induce vascular endothelial dysfunction and promoted the release of proinflammatory and procoagulant factors, mediated by miR-451a negative regulation of the interleukin 6 receptor/signal transducer and activator of transcription/transcription factor (IL6R/STAT/TF) signaling pathway.8688 Metal NPs, such as Au and Ag, can also penetrate the cell membrane, increase oxidative stress and decrease cell viability.89,90 Consequently, exposure to Au may cause nephrotoxicity91 and reversible cardiac hypertrophy.92 El-Hussainy and colleagues observed myocardial dysfunction in rats given alumina NPs.93,94 Nemmar and colleagues investigated the toxicity of ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs) administered intravenously, which resulted in cardiac oxidative stress and DNA damage as well as thrombosis.95 Cell-derived exosomes and a majority of natural polymers are considered relatively safe;83 however, Babiker and colleagues demonstrated that dendritic polyamidoamine NPs compromise recovery from ischemia/reperfusion (I/R) injury in isolated rat hearts.96 The effects of degradation byproducts are also of concern.83 An advantage of the nanoscale size of NPs is that their injection is unlikely to block the microvascular system; however, it remains controversial whether NPs give rise to arrhythmias.97 These factors highlight that examining the biocompatibility of NPs both in vitro and in vivo is a vital component of preclinical or clinical research.

NP toxicity depends on many parameters, including material composition, coating, size, shape, surface charges and concentration.39 For instance, larger particles seem to be more favorable from a toxicology standpoint.83 However, single-walled CNTs are considered more harmful than multi-walled CNTs, due to their smaller size resulting in less aggregation and increased uptake by macrophages.61 Cationic AuNPs are more toxic compared with anionic AuNPs, which appear to be nontoxic.98 Generally speaking, NP-associated toxicity can be lowered by functionalization with nontoxic surface molecules, stabilization and localization in the region of interest by using scaffolds.24,99 The toxicity of CNTs mediated by oxidative stress and inflammation was reduced using these strategies in several studies.24,100 Local application and targeted delivery also enabled dose reduction and concurrently decreased the incidence of adverse effects. Administration of therapeutic agents directly into the infarcted or peri-infarcted myocardium is a conventional approach with a low risk of inducing embolization.

NP is a suitable method for the administration of therapeutic agents in terms of the minimization of side effects, enhanced stability of cargo, and possibility of controlled delivery and release.76 Detailed information on the experimental design and results of the latest studies on the use of NPs as therapeutic vectors are provided in Table 1. Recently, several drugs approved for clinical use as immunosuppressants have been suggested as potentially effective cardioprotective agents. For example, NPs containing cyclosporine A inhibited apoptosis and inflammation in ischemic myocardium by improving mitochondrial function.25,101 Commercial methotrexate also showed minor cardioprotective effects; additionally, when loaded into lipid core NPs, adenosine bioavailability and echocardiographic and morphometric results were all improved a rats model of MI.102 Margulis and colleagues developed a method to fabricate NPs via a supercritical fluids setup, which loaded and transferred celecoxib, a lipophilic nonsteroidal anti-inflammatory drug, into the NPs. These celecoxib-containing NPs alleviated ejection function damage and ventricular dilation by inducing significant levels of neovascularization.103 Furthermore, a series of investigations indicated that drugs used for hypoglycemia (eg pioglitazone, exenatide and liraglutide)104106 and lipid lowering (statins)107 attenuate the progression of post-MI heart failure, and are therefore also potential therapeutic cargoes for NPs in the treatment of MI.

NP systems also offer an alternative method for delivering plant-derived therapeutic agents, most of which belong to traditional Chinese medicine. Its of vital importance because of the criticization on adverse reactions caused by direct injection of such complexes. Cheng and colleagues designed a dual-shell polymeric NP as a multistage, continuous, targeted vehicle of resveratrol, a reactive oxygen species (ROS) scavenger. Due to the severe oxide stress in areas of infarction, the proposed antioxidant-delivery NPs represent a new method to effectively treat MI. These NPs are modified with two peptides, targeting ischemic myocardium and mitochondria, respectively; cardioprotective effects have been confirmed in both hypoxia/reoxygenated (H/R) H9C2 cells and I/R rats.108 In addition, Dong and colleagues also demonstrated that puerarin-SLNs produced smaller areas of infarction in a MI rat model, evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. These particles were modified with cyclic arginyl-glycyl-aspartic acid peptide, a specific targeting moiety to v3 integrin receptors, which are highly expressed on endothelial cells (ECs) during angiogenesis.109 In a recent study, quercetin was loaded into mesoporous silica NPs, which enhanced the inhibition of cell apoptosis and oxidative stress, improving ventricular remodeling and promoting the recovery of cardiac function by activating the janus kinase 2 (JAK2)/STAT3 pathway.110 Similarly, curcuminpolymer NPs, administered by gavage, improved serum inflammatory cytokine levels compared with direct administration of curcumin.111

Translation of novel bioactive agents into clinical practice has been limited, owing to lack of sufficient bioavailability and systemic toxicity.76 Encapsulating small molecules such as 3i-1000 (an inhibitor of the GATA4NKX2-5 interaction),43 TAK-242 (inhibitor of toll-like receptor 4, TLR4)112 and C143 (inhibitor of ERK1/2)113 in NPs promotes myocardial repair after MI without the risk of uncontrolled and off-target adverse effects. Administration of vascular endothelial growth factor (VEGF) causes elevated vascular permeability and tissue edema. The cardioprotective effects of VEGF-loaded polymeric NPs injected either intravenously114 or intramyocardially115 eliminated vascular leakage due to promotion of lymphangiogenesis. Further studies have confirmed these results and add to the evidence that combined delivery of VEGF with other growth factors is recommended, since VEGF primarily drives the formation of new capillaries.116 Furthermore, in line with previous research, similar therapeutic effects have been demonstrated in studies using polymeric NPs loaded with stromal cell derived factor 1 (SDF-1) and insulin-like growth factor 1 (IGF-1).117,118

We also notice that some novel payloads in NPs-based therapy for MI have been studied. For example, deoxyribozyme-AuNP can silence tumor necrosis factor- (TNF-).119 A target that is implicated in irreversible heart damage after MI; its effects are mediated by free radical production, downregulation of contractile proteins, and initiation of pro-inflammatory cytokine cascades. Mesoporous iron oxide NPs containing the hydrogen sulfide donor compound diallyl trisulfide act as a platform for the controlled and sustained release of this therapeutic gas molecule. The application of these NPs at appropriate concentrations, resulted in the preservation of cardiac systolic performance without any observable detrimental effects on homeostasis in vivo.15

With increasing insight into the molecular mechanisms of MI, a particular emphasis on gene therapy has emerged. Gene expression can be modulated by DNA fragments, messenger RNA (mRNA), microRNA (miRNA) and small interfering RNA (siRNA), which thus represent new approaches for treating ischemia. Currently available nucleic acid delivery systems are mainly divided into viral and non-viral systems. However, virus-based approaches are limited by their potential for uncontrollable mutagenesis.36 From a clinical point of view, NP represents a suitable choice as novel non-viral nucleic acid vector, which could feasibly transfect in a stable, targeted, and sustained manner (as shown in Table 2).

Table 2 NPs-Based Nucleic Acid Delivery Systems for Treatment for MI Reported in the Last 7 Years

As a common gene vehicle, plasmids face the risk of being destroyed by DNase and immunoreactivity in the serum, and transduction in non-target organs.120 A recent study by Kim and colleagues aligns with current research trends focused on virus-free therapies, in which carboxymethylcellulose NPs were designed to transfer 5-azacytidine to halt proliferation, and deliver plasmid DNA containing GATA4, myocyte enhancer factor 2C (MEF2C), and TBX5 to induce reprogramming and cardiogenesis of mature normal human dermal fibroblasts.121 In a methodological study, lipidoid NPs were used to successfully deliver pseudouridine-modified mRNA, encoding enhanced green fluorescent protein.122

MiRNAs act as essential regulators of cellular processes through post-transcriptional suppression; increasing evidence reveals miRNAs play critical roles in cardiovascular diseases. An miRNA-transferring platform with self-accelerating nucleic acid release, containing a heparin core and an ethanolamine-modified poly(glycidyl methacrylate) shell, has been constructed and used as an efficient vector of miR-499, which inhibits cardiomyocyte apoptosis.123 Intravenous administration of anionic hyaluronan-sulfate NPs (mean diameter 130 nm) enable the stable delivery of miR-21 mimics, thus modulating the expression of TNF, transforming growth factor (TGF), and suppressor of cytokine signaling 1 (SOCS1). Consequently, these NPs switch the phenotype of macrophages from pro-inflammatory to reparative, promote neovascularization and reduced collagen deposition.124 Interestingly, silencing miR-21 using antagomiR-21a-5p in a nanoparticle formulation has also been shown to reduce expression of pro-inflammatory cytokines in vitro, and attenuate inflammation and fibrosis in mice with autoimmune myocarditis.125 A number of other potentially therapeutic miRNAs have also been successfully transferred to CMs in recent works, including miR-146a, miR-146b-5p, miR-181b, miR-199-3p, miR-214-3p, miR-194-5p and miR-122-5p.126128 Evaluation of angiogenesis, cardiac function, and scar size in these studies indicated that injectable miRNANPs can deliver miRNA to restore injured myocardium efficiently and safely. Yang and colleagues developed an in vivo miRNA delivery system incorporating a shear-thinning hydrogel and NPs characterized by surface presence of miRNA and cell-penetrating peptide (CPP).126 Additionally, angiotensin II type 1 receptor-targeting peptide-modified NPs serve as targeted carriers for anti-miR-1 antisense oligonucleotide, significantly reducing apoptosis and infarct size.129

SiRNAs inhibit gene expression by mediating mRNA cleavage in a sequence-specific manner, highlighting NP-based RNA interference as another viable approach to modulate cellular phenotype and attenuate cardiac failure. Dosta and colleagues demonstrated that poly(-amino ester) particles modified by adding lysine-/histidine-oligopeptides could represent a system for the transfer of siRNA.130 Studies have now revealed that chemokine CC motif ligand 2 (CCL2) and its cognate receptor CC chemokine receptor 2 (CCR2) promoted excessive Ly6Chigh inflammatory monocyte infiltration in infarcted area and aggravate myocardial injury.131 Photoluminescent mesoporous silicon nanoparticles (MSNPs) carrying siCCR2 have been reported to improve the effectiveness of transplanted mesenchymal stem cells (MSCs) in reducing myocardial remodeling after acute MI.131 Targeted transportation and enhanced uptake with minimum leakage improved the efficiency of delivery via NPs, significantly outperforming the control group. Taken together, these studies demonstrate that NPs act as promising drug delivery systems in the treatment of MI.

Myocardial patches and scaffolds, consisting of either bioactive hydrogels or nanofibers, are minimally invasive, relatively localized, and targeted approaches to repair the heart after IHD. Those biomaterials must have an anisotropic structure, mechanical elasticity, electrical conductivity, and the ability to promote ischemic heart repair.132 A variety of NPs have been applied in this field, among which inorganic NPs have been the focus of most research efforts.42 These investigations of inorganic NPs can be divided into four categories based on their effects and the mechanisms involved, which are described in this section.

NPs enhance physical properties and electroconductivity, which is essential for the biomaterials to properly accommodate cardiac cells and subsequently resulted in cell retention, cell-cell coupling and robust synchronized beating behavior. CNTs are able to increase the required physical properties of scaffolds, such as maximum load, elastic modulus, and toughness.133,134 Gelatin methacrylate (GelMA) also has decreased impedance, hydrogel swelling ratio, and pore diameter, as well as increased Youngs modulus when combined with gold nanorods (AuNRs).135 Given this insight, highly electroconductive NPs have been increasingly investigated.34,99 Specifically, Ahadian and colleagues revealed that a higher integrated CNT concentration in gels resulted in greater conductivity.136 Zhou and colleagues verified the therapeutic effects of patches incorporating single-walled CNT for myocardial ischemia, which halted progressive cardiac dysfunction and regenerated the infarcted myocardium.137 Spherical AuNPs have also been shown to increase the conductivity of chitosan hydrogels in a concentration-dependent manner.138 Interestingly, silicon NPs mimic the effects of AuNRs without affecting conductivity or stiffness, as reported by Navaei and colleagues.139

Several studies demonstrate the effects of CNT on CM functions. When CMs are cultured on multi-walled CNT substrates or treated with CNT-integrated patches, these cells show spontaneous electrical activity.34,99,140 Brisa and colleagues functionalized reverse thermal gels with AuNPs, investigating the phenotype of CMs in vitro; the growth of cells with a CM phenotype was observed, along with gap junction formation.141 CMs exposed to AuNR-containing GelMa show higher affinity, leading to packed and uniform tissue structure.135 These conductive scaffolds also facilitate the robustness and synchrony of spontaneous beating in CMs without damaging their viability and metabolic activity.

Combined incorporation of inorganic NPs and cells represents a feasible strategy to promote therapeutic effects. Despite some reports on the cytotoxicity of Au,89,90 no significant loss of viability, metabolism, migration, or proliferation of MSCs in scaffolds containing AuNP is reported. A CNT-embedded, electrospun chitosan/polyvinyl alcohol mesh is reported to promote the differentiation of MSCs to CMs.142 In another approach, Baei and colleagues added AuNPs to chitosan thermosensitive hydrogels seeded with MSCs.138 There was a significant increase in expression of early and mature cardiac markers, indicating enhanced cardiomyogenic differentiation of MSCs compared to the matrix alone, while no difference in growth was observed. Gao et al created a fibrin scaffold, in which cells and AuNPs were suspended simultaneously; these bioactive patches were shown to promote left ventricular function and decrease infarct size and apoptosis in the periscar boarder zone myocardium in swine models of acute MI.97 These studies of AuNP-containing scaffolds demonstrated reduced infarct and fibrotic size, as well as facilitated angiogenesis and cardiac function, which can be attributed at least in part to the enhanced expression of connexin 43 and atrial natriuretic peptide, and activation of the integrin-linked kinase(ILK)/serine-threonine kinase (p-AKT)/GATA4 pathway.49,143,144 Scaffolds containing Ag NPs evoke M2 polarization of macrophages in vitro;145 which may also play a role in cardioprotective action because M2 macrophages are capable of promoting cardiac recovery via the secretion of anti-inflammatory cytokines, collagen deposition, and neovascularization.146

Similarly, CNT also act synergically with poly(N-isopropylacrylamide) scaffolds containing adipose-derived stem cells;147 significant improvement of cardiac function and increased implantation and proliferation of stem cells has been observed with these scaffolds, compared with scaffolds without CNT.147 Selenium NPs148 and titania NPs53 have been shown to improve the mechanical and conductive properties of chitosan patches, promoting their ability to support proliferation and the synchronous activity of cells growing on these patches.

Mounting evidence demonstrates the unique benefits of using cardiac scaffolds with magnetic NPs such as SPIONs; these benefits include, but are not limited to, significant improvements in cell proliferation149 and assembly of electrochemical junctions.150 Given that magnetic manipulation enhances the therapeutic efficacy of iron oxide NPs in cardiac scaffolds, Chouhan and colleagues designed a magnetic actuator device by incorporating magnetic iron oxide NPs (MIONs) in silk nanofibers; this resulted in more controlled drug release properties, as well as the promotion of proliferation and maturation in CMs.151 Magnetic NPs can be used to label induced pluripotent stem cell (iPSC)-derived CMs via conjugation with antibodies against signal-regulatory protein . Zwi-Dantsis and colleagues reported the construction of tailored cardiac tissue microstructures, achieved by orienting MION-labelled cells along the applied field to impart different shapes without any mechanical support.152 However, the interactions between and effects of NPs and cells in scaffolds, and the cardioprotective efficacy of patches in which NP-labelled cells are suspended, require further elucidation.

Polymeric nanomaterials have also been investigated in the context of cardiac bioengineering materials; for instance, water-swollen polymer NPs have been used to prepare nanogels. With a 3D structure containing cross-linked biopolymer networks, nanogels can encapsulate, protect, and deliver various agents.83,153 PDA-coated tanshinone IIA NPs suspended in a ROS-sensitive, injectable hydrogel via PDA-thiol bonds significantly improved cardiac performance, accompanied by inhibition of the expression of inflammation factors in rat model.73 After implanting cryogel patches consisting of GelMa and linked conductive polypyrrole NPs154 or scaffolds of electrospun GelMA/polycaprolactone with GelMA-polypyrrole NPs,155 left ventricular (LV) ejection fraction (EF) has been shown to increase, with a concurrent decrease in infarct size, in MI animal models.

Progenitor or stem cell-based therapy in the form of injections and engineered cardiac patches, discussed in the previous section, has been recognized as a promising strategy to improve the cardiac niche and ameliorate adverse remodeling processes and fibrosis after acute MI.56,156,157 However, poor survival and low engraftment rates for transplanted cells are still major challenges in this field.157 Among possible optimization strategies, combining NPs with stem cell therapy is of great interest (Table 3).

Table 3 Studies Combining NPs and Cell Therapy Reported in the Last 7 Years

Accumulating evidence has shown two main mechanisms for NP-loaded cell therapy in the context of MI treatment. Firstly, various NP types could efficiently improve survival and cell proliferation, modulating differentiation of implanted cells in the ischemic microenvironment.62,158 Specifically, electrically driven nanomanipulators could guide cardiomyogenic differentiation of MSCs: in a previous study, electroactuated gold NPs were administrated with pulsed electric field stimulation, and tube-like morphological alterations were observed, along with upregulation of cardiac specific markers.143 Adipose-derived stem cells that load PLGA-simvastatin NPs promoted differentiation of these cells into SMCs and ECs, and had cardioprotective effects in a mouse model of MI induced by left anterior descending ligation.17 Secondly, engraftment rate is another important factor affecting treatment efficacy in this context.159 Zhang and colleagues designed silica-coated, MION-labelled endothelial progenitor cells; intravenous administration of these cells in a rat model of MI significantly improved cardiac performance, as indicated by echocardiogram, morphological, and histological evidence, and neovascularization. This indicates magnetic guidance may potentially address the problem of low levels of stem cell retention, which has typically been observed.51 In particular, NPs can link the therapeutic cells to injured CMs, thereby promoting cell anchorage and engraftment. To this end, Cheng and colleagues established a magnetic, bifunctional cell connector by conjugating NPs with two antibodies: one against cell determinant (CD)45, which is expressed on bone marrow-derived stem cells, and one against MLC. The magnetic core of this NP also enabled physical enrichment in ischemic heart tissue using external magnets.160 More than one mechanism may be involved in a study. Chen and colleagues fabricated a sustained release carrier of insulin-like growth factor (IGF), a pro-survival agent, via in situ growth of Fe3O4 NPs on MSNPs. In this study, the NPs promoted both the survival and retention of MSCs, and intramyocardial injection of the NP-labeled MSCs was able to ameliorate functional and histological damage without any obvious toxicity in vivo.161 However, SPION labeling does not seem to improve therapeutic efficiency, as demonstrated by Wang and colleagues in a study using hypoxia-preconditioned SPION-labeled adipose-derived stem cells (ASCs).162

Primary criticisms of cell-based therapies include their potential immunogenicity, arrhythmogenicity and tumorigenicity. It is widely accepted that the beneficial effects of cell-based therapy are mainly attributable to paracrine effects rather than directly replenishing lost CMs;56 researchers are therefore investigating of cell-free approaches. Exosomes have attractive properties including stable transport, homing to target tissues or cells, and penetration of biological barriers, as well as being more biocompatible with lower immunogenicity than cell-based approaches. Interestingly, post-MI circulating exosomes serve as important cardioprotective messengers.163,164 Manipulating their biodistribution has proven to be a viable strategy to reduce infarct size, promoting angiogenesis and ejection functions.21 However, from a therapeutic standpoint, the lack of control over endogenous exosome production and cargo encapsulation limits the use of this naturally-present mechanism for therapeutic enhancement. The low purity and weak targeting of natural exosomes are two further obstacles to overcome before clinical application. Strategies to address these include finding robust sources; optimized isolation methods for higher yields, efficiency and purity; and improving therapeutic payloads. These have been systematically summarized in other reviews.165167

AS is considered a low-grade, chronic inflammatory disease, characterized by accumulation and deposition of cholesterol in arteries, as well as remodeling of the extracellular matrix in the intima and inner media.12,168 Inflammation of ECs, proliferation of SMCs, and recruitment of monocytes and macrophages play a critical role in the development of AS. NPs allow for the packaging of large amounts of therapeutic compounds in a compact nanostructure, specifically targeting pathological mechanisms and attenuating atherogenesis. Optimization of the loaded drug and NP target together lead to enhanced efficacy while minimizing side effects.169 In this section, we summarize recent breakthroughs in the order of pathological progression, as shown in Table 4.

Primary prevention refers to control of the risk factors of AS, one of which is hypertension.170 PLA NPs have been shown to improve the efficacy of aliskiren, the first oral direct renin inhibitor and the first in a new class of antihypertensive agents.29 Encapsulation in nanocarriers also renders the application of anandamide viable, which was once limited; recent research revealed that this new therapy could lower blood pressure and LV mass index in rats.171 Similar results were observed in a study in which angiotensinogen was silenced using small hairpin RNA.172 NPs may also help to make more anti-hypertensive drugs available, reduce side effects such as asthma, and lessen the effective dosage by providing sustained drug release over time. The link between AS and diabetes mellitus, which describes a group of metabolic disorders, has also been investigated in numerous studies.173 Possible mechanisms include oxidative stress, altered protein kinase signaling, and epigenetic modifications. Cetin and colleagues successfully constructed NP-based drug delivery systems for the administration of metformin, an oral antihyperglycemic agent with low oral bioavailability and short biological half-life.174 NPs are also promising tools for improving the oral bioavailability of insulin, which is of great interest because oral insulin will significantly increase patients compliance.175,176

The inflammatory hypothesis of AS is now widely established, making selective targeting and accumulation of NPs in inflammatory lesions attractive therapeutic strategies. Targeting macrophages in apoE-/- mice has been shown to result in decreased phagocytosis and suppression of inflammatory genes in lesional macrophages, thus lessening burden of atherosclerotic plaques.177 Tom and colleagues used NPs consisting of high-density lipoprotein (HDL), a known atheroprotective bionanomaterial, as carriers for TNF receptor-associated factor in mice, and observed reductions in both leukocyte recruitment and macrophage activation.178 Both single-walled CNT and HDL-NPs have a favorable safety profile. In a pathological context, activated endothelial tissue expresses more adhesion molecules, such as selectins, than usual. These molecules are thus potential targets for cardiovascular nanomedicine. Glycoprotein Ib (GPIb)179 and biotinylated Sialyl Lewis A (sLeA)69 specifically bind to selectins, leading to the accumulation of conjugated NPs in injured vessels; an in vitro study demonstrated that GPIb-conjugated NPs could bind to target surfaces, where they were taken up by activated ECs under shear stress conditions. In another study, Sager and colleagues simultaneously inhibited five adhesion molecules associated with leukocyte recruitment in post-MI apoE-/- mice. Inflammation in plaque and ischemic heart, rendering acute coronary events and post-MI complications less likely to occur.180 However, targeting inflammatory process may have heterogeneous effects in humans because the targeting moieties and target receptors may be overexpressed in several different pathologic conditions in addition to AS. Oxidation is another factor involved in the development of AS. Upregulation of endothelial nitric oxide synthase (eNOS) leads to vascular construction and other AS-promoting effects. Pechanova and colleagues observed that the application of PLA NPs resulted in larger decreases in NOS than direct administration.29

Aside from these processes, avoiding plaque rupture and thrombosis could be another therapeutic aim. Nakashiro and colleagues showed that delivering pioglitazone via NPs inhibited plaque rupture in apoE-/- mice.181 The integrin 3 is upregulated in angiogenic vasculature, which is ubiquitous in plaque ruptures, which may lead to MI.182 3 integrin-targeted NPs provide a site-specific drug delivery platform that has been shown to successfully stabilize plaques in rabbits.182 Ji and colleagues used NPs composed of albumin with an average diameter of 225.6 nm to deliver a plasmid containing the tissue-type plasminogen activator gene (t-PA); this system plays a role in preventing thrombosis in addition to attenuating intimal thickness and proliferation of vascular SMCs.183 NPs consisting of engineered amphipathic cationic peptide and serine/threonine protein kinase JNK2 siRNA also reduces thrombotic risk, plaque necrotic area, and vascular barrier disorder in mice given the equivalent of a 14-week western diet.184

Innovation and development of therapies based on NPs in recent years has led to significant advances towards complete repair of the injured myocardium following acute MI. Nevertheless, developing clinically relevant solutions remains difficult for several reasons. Firstly, as shown in tables, there is little consistency among studies regarding the characteristics of NPs, their payloads, and their methods of administration, as well as methods used for evaluating cardiac repair. It can be difficult to control characteristics such as the size of the synthesized particles in a narrow range, even within single studies. Such significant heterogeneity can lead to differences in observed results in repeated experiments, or under different conditions. Secondly, although many studies have focused on the health effects of unintentional exposure to NPs by inhalation or ingestion,185,186 most of the studies on medical applications of NPs have not reported on toxicity of NP systems until recently.73 Remarkably, there has not been a consensus on NP-associated adverse effects in existing reports, making assessments of biocompatibility a priority for NP characterization.

NPs have emerged as a powerful tool for controlling cell signaling pathways in regenerative strategies using novel therapeutics and drugs that are unsuitable for direct administration. One advantage of the application of NP systems is the ability to release the drug payload or regulate gene expression in a stable and controlled manner. Therefore, many otherwise serious side effects, such as sudden arrhythmic deaths resulting from persistent and uncontrolled expression of miRNA by viral vectors, may be completely avoided.187 More research is required to develop stable and efficient methods of NP production, improve encapsulation efficiency of drugs, and achieve satisfactory targeting. In particular, a greater focus on investigating NP-based switches, including optical, electrical and magnetic methods, has enabled the regulation of cell signaling, exemplified by the development of a CuS NP-based photothermal switch.52 Optimizing tissue engineering scaffolds containing conductive NPs is a promising strategy for the protection of the myocardium after ischemia by mimicking the myocardial extracellular matrix. Improvements in understanding of cardiac repair mechanisms, and how these biomaterials may interfere with them, is therefore urgently needed. Furthermore, heart repair is complex and involves many processes, including apoptosis, angiogenesis, inflammatory infiltration, and fibrosis. Therefore, novel treatments should be designed using NP-based integrative strategies based on these multiple different mechanisms. However, its important to highlight that synergistic effects of different drug payloads, NPs, and NPcell combined strategies should be addressed, as not all may be compatible with one another. Future research should focus on these aspects to translate NP-based therapeutic strategies for MI into practical and effective clinical use.

The authors report no conflicts of interest in this work.

1. Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet. 2017;389(10065):197210. doi:10.1016/s0140-6736(16)30677-8

2. Marn-Juez R, El-Sammak H, Helker CSM, et al. Coronary revascularization during heart regeneration is regulated by epicardial and endocardial cues and forms a scaffold for cardiomyocyte repopulation. Dev Cell. 2019;51(4):503515.e4. doi:10.1016/j.devcel.2019.10.019

3. Rentrop KP, Feit F. Reperfusion therapy for acute myocardial infarction: concepts and controversies from inception to acceptance. Am Heart J. 2015;170(5):971980. doi:10.1016/j.ahj.2015.08.005

4. Arbab-Zadeh A, Nakano M, Virmani R, Fuster V. Acute coronary events. Circulation. 2012;125(9):11471156. doi:10.1161/circulationaha.111.047431

5. Ou LC, Zhong S, Ou JS, Tian JW. Application of targeted therapy strategies with nanomedicine delivery for atherosclerosis. Acta Pharmacol Sin. 2021;42(1):1017. doi:10.1038/s41401-020-0436-0

6. Gorabi AM, Kiaie N, Reiner , Carbone F, Montecucco F, Sahebkar A. The therapeutic potential of nanoparticles to reduce inflammation in atherosclerosis. Biomolecules. 2019;9(9):2545. doi:10.3390/biom9090416

7. Young DR, Hivert MF, Alhassan S, et al. Sedentary behavior and cardiovascular morbidity and mortality: a science advisory from the American Heart Association. Circulation. 2016;134(13):e26279. doi:10.1161/cir.0000000000000440

8. Ekroos K, Jnis M, Tarasov K, Hurme R, Laaksonen R. Lipidomics: a tool for studies of atherosclerosis. Curr Atheroscler Rep. 2010;12(4):273281. doi:10.1007/s11883-010-0110-y

9. Meneghini BC, Tavares ER, Guido MC, et al. Lipid core nanoparticles as vehicle for docetaxel reduces atherosclerotic lesion, inflammation, cell death and proliferation in an atherosclerosis rabbit model. Vascul Pharmacol. 2019;115:4654. doi:10.1016/j.vph.2019.02.003

10. Bulgarelli A, Martins Dias AA, Caramelli B, Maranho RC. Treatment with methotrexate inhibits atherogenesis in cholesterol-fed rabbits. J Cardiovasc Pharmacol. 2012;59(4):308314. doi:10.1097/FJC.0b013e318241c385

11. Cervadoro A, Palomba R, Vergaro G, et al. Targeting inflammation with nanosized drug delivery platforms in cardiovascular diseases: immune cell modulation in atherosclerosis. Front Bioengineering Biotechnol. 2018;6:177. doi:10.3389/fbioe.2018.00177

12. Zhang J, Zu Y, Dhanasekara CS, et al. Detection and treatment of atherosclerosis using nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017;9(1). doi:10.1002/wnan.1412

13. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):21082121. doi:10.1056/NEJMoa1809615

14. Bahadur S, Sachan N, Harwansh RK, Deshmukh R. Nanoparticlized system: promising approach for the management of alzheimers disease through intranasal delivery. Curr Pharm Des. 2020;26(12):13311344. doi:10.2174/1381612826666200311131658

15. Wang W, Liu H, Lu Y, et al. Controlled-releasing hydrogen sulfide donor based on dual-modal iron oxide nanoparticles protects myocardial tissue from ischemia-reperfusion injury. Int J Nanomedicine. 2019;14:875888. doi:10.2147/ijn.S186225

16. Banik B, Surnar B, Askins BW, Banerjee M, Dhar S. Dual-targeted synthetic nanoparticles for cardiovascular diseases. ACS Appl Mater Interfaces. 2020;12(6):68526862. doi:10.1021/acsami.9b19036

17. Yokoyama R, Ii M, Masuda M, et al. Cardiac regeneration by statin-polymer nanoparticle-loaded adipose-derived stem cell therapy in myocardial infarction. Stem Cells Transl Med. 2019;8(10):10551067. doi:10.1002/sctm.18-0244

18. Wang J, Xiang B, Deng J, et al. Externally applied static magnetic field enhances cardiac retention and functional benefit of magnetically iron-labeled adipose-derived stem cells in infarcted hearts. Stem Cells Transl Med. 2016;5(10):13801393. doi:10.5966/sctm.2015-0220

19. Gadde S, Rayner KJ. Nanomedicine Meets microRNA: current Advances in RNA-Based Nanotherapies for Atherosclerosis. ACS Nano. 2016;36(9):e739. doi:10.1161/atvbaha.116.307481

20. Sun Y, Lu Y, Yin L, Liu Z. The roles of nanoparticles in stem cell-based therapy for cardiovascular disease. Int J Nanomedicine. 2020;8:947. doi:10.3389/fbioe.2020.00947

21. Liu S, Chen X, Bao L, et al. Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles. Nat Biomed Eng. 2020;4(11):10631075. doi:10.1038/s41551-020-00637-1

22. Pitek AS, Wang Y, Gulati S, et al. Elongated plant virus-based nanoparticles for enhanced delivery of thrombolytic therapies. Mol Pharm. 2017;14(11):38153823. doi:10.1021/acs.molpharmaceut.7b00559

23. Won YW, McGinn AN, Lee M, Bull DA, Kim SW. Targeted gene delivery to ischemic myocardium by homing peptide-guided polymeric carrier. Article. Mol Pharm. 2013;10(1):378385. doi:10.1021/mp300500y

24. Sink E, Narayan SP, Abdel-Hafiz M, Mestroni L, Pea B. Nanomaterials for cardiac tissue engineering. Molecules. 2020;25(21). doi:10.3390/molecules25215189

25. Zhang CX, Cheng Y, Liu DZ, et al. Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats. J Nanobiotechnology. 2019;17(1):18. doi:10.1186/s12951-019-0451-9

26. Oduk Y, Zhu W, Kannappan R, et al. VEGF nanoparticles repair the heart after myocardial infarction. Am J Physiol Heart Circ Physiol. 2018;314(2):H278h284. doi:10.1152/ajpheart.00471.2017

27. Caldas M, Santos AC, Veiga F, Rebelo R, Reis RL, Correlo VM. Melanin nanoparticles as a promising tool for biomedical applications - a review. Acta biomaterialia. 2020;105:2643. doi:10.1016/j.actbio.2020.01.044

28. Wang X, Wang C, Wang X, Wang Y, Zhang Q, Cheng Y. A polydopamine nanoparticle-knotted poly(ethylene glycol) hydrogel for on-demand drug delivery and chemo-photothermal therapy. Chem Mater. 2017;29(3):13701376. doi:10.1021/acs.chemmater.6b05192

29. Pechanova O, Barta A, Koneracka M, et al. Protective effects of nanoparticle-loaded aliskiren on cardiovascular system in spontaneously hypertensive rats. Molecules. 2019;24(15):2710. doi:10.3390/molecules24152710

30. Mao S, Wang L, Chen P, Lan Y, Guo R, Zhang M. Nanoparticle-mediated delivery of Tanshinone IIA reduces adverse cardiac remodeling following myocardial infarctions in a mice model: role of NF-B pathway. Artif Cells, Nanomed Biotechnol. 2018;46(sup3):S707s716. doi:10.1080/21691401.2018.1508028

31. Guex AG, Kocher FM, Fortunato G, et al. Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development. Acta biomaterialia. 2012;8(4):14811489. doi:10.1016/j.actbio.2011.12.033

32. Bae S, Park M, Kang C, et al. Hydrogen peroxide-responsive nanoparticle reduces myocardial ischemia/reperfusion injury. J Am Heart Assoc. 2016;5(11). doi:10.1161/jaha.116.003697

33. Wu S, Duan B, Qin X, Butcher JT. Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering. Acta biomaterialia. 2017;51:89100. doi:10.1016/j.actbio.2017.01.051

34. Pok S, Vitale F, Eichmann SL, Benavides OM, Pasquali M, Jacot JG. Biocompatible carbon nanotube-chitosan scaffold matching the electrical conductivity of the heart. ACS Nano. 2014;8(10):98229832. doi:10.1021/nn503693h

35. Zhu K, Wu M, Lai H, et al. Nanoparticle-enhanced generation of gene-transfected mesenchymal stem cells for in vivo cardiac repair. Biomaterials. 2016;74:188199. doi:10.1016/j.biomaterials.2015.10.010

36. Singh B, Garg T, Goyal AK, Rath G. Recent advancements in the cardiovascular drug carriers. Artif Cells, Nanomed Biotechnol. 2016;44(1):216225. doi:10.3109/21691401.2014.937868

37. Jung H, Jang MK, Nah JW, Kim YB. Synthesis and Characterization of Thermosensitive Nanoparticles Based on PNIPAAm Core and Chitosan Shell Structure. Article. Macromol Res. 2009;17(4):265270. doi:10.1007/bf03218690

38. Paliwal R, Paliwal SR, Kenwat R, Kurmi BD, Sahu MK. Solid lipid nanoparticles: a review on recent perspectives and patents. Expert Opin Ther Pat. 2020;30(3):179194. doi:10.1080/13543776.2020.1720649

39. Piperigkou Z, Karamanou K, Engin AB, et al. Emerging aspects of nanotoxicology in health and disease: from agriculture and food sector to cancer therapeutics. Food Chem Toxicol. 2016;91:4257. doi:10.1016/j.fct.2016.03.003

40. Chen W, Jarzyna PA, van Tilborg GA, et al. RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe. FASEB j. 2010;24(6):16891699. doi:10.1096/fj.09-139865

41. Nguyen J, Sievers R, Motion JP, Kivime S, Fang Q, Lee RJ. Delivery of lipid micelles into infarcted myocardium using a lipid-linked matrix metalloproteinase targeting peptide. Mol Pharm. 2015;12(4):11501157. doi:10.1021/mp500653y

42. Ashtari K, Nazari H, Ko H, et al. Electrically conductive nanomaterials for cardiac tissue engineering. Adv Drug Deliv Rev. 2019;144:162179. doi:10.1016/j.addr.2019.06.001

43. Kinnunen SM, Tlli M, Vlimki MJ, et al. Cardiac Actions of a Small Molecule Inhibitor Targeting GATA4-NKX2-5 Interaction. Sci Rep. 2018;8(1):4611. doi:10.1038/s41598-018-22830-8

44. Dong Y, Hong M, Dai R, Wu H, Zhu P. Engineered bioactive nanoparticles incorporated biofunctionalized ECM/silk proteins based cardiac patches combined with MSCs for the repair of myocardial infarction: in vitro and in vivo evaluations. Sci Total Environ. 2020;707:135976. doi:10.1016/j.scitotenv.2019.135976

45. Ramirez-Lee MA, Aguirre-Bauelos P, Martinez-Cuevas PP, et al. Evaluation of cardiovascular responses to silver nanoparticles (AgNPs) in spontaneously hypertensive rats. Nanomedicine. 2018;14(2):385395. doi:10.1016/j.nano.2017.11.013

46. Sharma AK, Kumar A, Sahu M, Sharma G, Datusalia AK, Rajput SK. Exercise preconditioning and low dose copper nanoparticles exhibits cardioprotection through targeting GSK-3 phosphorylation in ischemia/reperfusion induced myocardial infarction. Microvasc Res. 2018;120:5966. doi:10.1016/j.mvr.2018.06.003

47. Zhang T, Dang M, Zhang W, Lin X. Gold nanoparticles synthesized from Euphorbia fischeriana root by green route method alleviates the isoprenaline hydrochloride induced myocardial infarction in rats. J Photochem Photobiol B. 2020;202:111705. doi:10.1016/j.jphotobiol.2019.111705

48. Tian A, Yang C, Zhu B, et al. Polyethylene-glycol-coated gold nanoparticles improve cardiac function after myocardial infarction in mice. Can J Physiol Pharmacol. 2018;96(12):13181327. doi:10.1139/cjpp-2018-0227

49. Hosoyama K, Ahumada M, Variola F, et al. Nanoengineered Electroconductive Collagen-Based Cardiac Patch for Infarcted Myocardium Repair. ACS Appl Mater Interfaces. 2018;10(51):4466844677. doi:10.1021/acsami.8b18844

50. You JO, Rafat M, Ye GJ, Auguste DT. Nanoengineering the heart: conductive scaffolds enhance connexin 43 expression. Nano Lett. 2011;11(9):36433648. doi:10.1021/nl201514a

51. Zhang BF, Jiang H, Chen J, Hu Q, Yang S, Liu XP. Silica-coated magnetic nanoparticles labeled endothelial progenitor cells alleviate ischemic myocardial injury and improve long-term cardiac function with magnetic field guidance in rats with myocardial infarction. J Cell Physiol. 2019;234(10):1854418559. doi:10.1002/jcp.28492

52. Gao W, Sun Y, Cai M, et al. Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis. Nat Commun. 2018;9(1):231. doi:10.1038/s41467-017-02657-z

53. Liu N, Chen J, Zhuang J, Zhu P. Fabrication of engineered nanoparticles on biological macromolecular (PEGylated chitosan) composite for bio-active hydrogel system in cardiac repair applications. Int J Biol Macromol. 2018;117:553558. doi:10.1016/j.ijbiomac.2018.04.196

54. Zheng Y, Zhang H, Hu Y, Bai L, Xue J. MnO nanoparticles with potential application in magnetic resonance imaging and drug delivery for myocardial infarction. Int J Nanomedicine. 2018;13:61776188. doi:10.2147/ijn.s176404

55. Xiong YY, Gong ZT, Tang RJ, Yang YJ. The pivotal roles of exosomes derived from endogenous immune cells and exogenous stem cells in myocardial repair after acute myocardial infarction. Theranostics. 2021;11(3):10461058. doi:10.7150/thno.53326

56. Huang P, Wang L, Li Q, et al. Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19. Cardiovasc Res. 2020;116(2):353367. doi:10.1093/cvr/cvz139

57. Zhang LL, Xiong YY, Yang YJ. The vital roles of mesenchymal stem cells and the derived extracellular vesicles in promoting angiogenesis after acute myocardial infarction. Stem Cells Dev. 2021;30(11):561577. doi:10.1089/scd.2021.0006

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Therapy and Prevention Strategies for Myocardial Infarction | IJN - Dove Medical Press

Recommendation and review posted by Bethany Smith

Learn how these advanced 3D tissue models generated on the Mantarray platform can improve the physiological relevance of preclinical cardiac and skeletal muscle models, accelerating the discovery of new medicines.

TORONTO (PRWEB) October 05, 2021

3D cellular models and organs-on-chips are poised to add tremendous value by providing human data earlier in the drug discovery pipeline. There is intense interest in adopting these 3D models in preclinical and translational research, but their complex implementation has remained a roadblock for many labs.

In this webinar, Curi Bio will present its Mantarray platform, which represents an easy-to-use, flexible, and scalable system for generating 3D EMTs at high-throughput with the ability to measure contractility in parallel. The platform features a novel method of casting 3D tissues that can be easily performed by nearly any cell biology researcher and can be readily adapted to a variety of cell lines and extracellular matrices. In addition, Mantarrays novel magnetic sensing modality permits contractility measurement of 24 tissues in parallel and in real time, while the cloud data analysis portal takes the guesswork out of analyzing and comparing results across experiments.

Register for this webinar to hear an overview of the technology, along with application examples across various use cases, including:

Learn how these advanced 3D tissue models generated on the Mantarray platform can improve the physiological relevance of preclinical cardiac and skeletal muscle models, accelerating the discovery of new medicines.

Join Dr. Nicholas Geisse, Chief Science Officer at Curi Bio, for the live webinar on Friday, October 22, 2021 at 1pm EDT.

For more information, or to register for this event, visit Mantarray: Scalable Human-Relevant 3D-Engineered Cardiac and Skeletal Muscle Tissues for Safety and Efficacy Studies.

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Mantarray: Scalable Human-relevant 3D Engineered Cardiac and Skeletal Muscle Tissues for Therapeutics Discovery Upcoming Webinar Hosted by Xtalks -...

Recommendation and review posted by Bethany Smith

Today is International Heart Day, and Cosmos is looking back on the stories that make our hearts flutter.

Scientists have taken another step in the quest to create a Google map of the human body by putting together a detailed cellular and molecular map of the healthy heart.

An international team analysed almost half a million individual cells and cell nuclei from six different regions of the heart, obtained from 14 organ donors whose hearts were healthy but unsuitable for transplantation.

The result is theHeart Cell Atlas, which, shows the huge diversity of cells and reveals heart muscle cell types, cardiac protective immune cells and an intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.

Sometimes, the heart just stops for no perceivable reason. Sudden cardiac arrest (SCA) is a prevalent hidden killer, even for younger people: 40% of those who die from SCA are under 50 years old.

SCA is not as rare as we would like it to be, says cardiologist Elizabeth Paratz, whos undertaking her PhD at the Baker Heart and Diabetes Institute, Melbourne. In the last year in Victoria, 750 young people under 50 have suffered an SCA. This is almost exactly five times the road toll over the same time in this age group, yet we hear a lot more publicity about road fatalities in young people.

Paratz is researching the prevalence and causes of SCA, as well as looking at ways to diagnose it better. There are multiple causes of SCA, and theyre hard to pinpoint in young people.

The controversial use of stem cells to help patients recover from a heart attack may work, but not because it grows new heart muscle.

Research in mice has found that injecting stem cells into the heart triggers an immune response that makes the scar stronger and the heart beat more forcefully.

Thestudy, published in the journalNature, suggests the current practice of injecting stem cells into a patients blood may not be optimal: direct injection into the heart could be more effective.

In a preclinical trial on a beating human heart, researchers have found that a drug candidate developed from the venom of the worlds deadliest spider, the funnel web, may hold promise for heart attack treatment and transplants.

The researchers, led by Meredith Redd of the University of Queensland (UQ), and Sarah Scheuer of Victor Chang Cardiac Research Institute, tested a protein called Hi1a, found in the Fraser Island (Kgari) funnel web venom, on a beating heart that had been exposed to heart attack stresses.

After a heart attack, blood flow to the heart is reduced, resulting in a lack of oxygen to heart muscle, says Nathan Palpant of UQ, corresponding author of the paper.

The lack of oxygen causes the cell environment to become acidic, which combine to send a message for heart cells to die.

The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival.

The Chinese Finger Trap a tubular braided novelty beloved by kids and pranksters around the world provided the inspiration for a nifty bit of biotech that looks set to save sick kids a whole lot of heartache. Literally.

Pedro del Nido from Boston Childrens Hospital in the US heads a team that has designed a proof-of-concept device that promises to dramatically cut down on surgery for children with certain types of heart defects.

At present, kids with defective mitral and tricuspid heart valves must undergo surgery in which a corrective implant is installed. The problem, however, is that children grow: the heart increases in size, and requires at least one, and often several, further surgical interventions so that a correspondingly larger implant can be installed.

Needless to say, these repeated bouts of open-heart surgery are extremely traumatic and disruptive.

Now, however, Nido and Karp may have come up with an elegant and clever solution: an implant that grows with the organ.

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Five Heart Stories For International Heart Day - Cosmos

Recommendation and review posted by Bethany Smith

SYDNEY, Oct. 5, 2021 /PRNewswire/ -- Clinical stage drug development company Pharmaxis Ltd (ASX: PXS) today announced further positive results of data analysis from a phase 1c clinical trial (MF-101) studying its drug PXS-5505 in patients with the bone marrow cancer myelofibrosis for 28 days at three dosage levels.

Assessment with Pharmaxis' proprietary assays of the highest dose has shown inhibition of the target enzymes, LOX and LOXL2, at greater than 90% over a 24-hour period at day 7 and day 28. The trial safety committee has reviewed the results and having identified no safety signals, has cleared the study to progress to the phase 2 dose expansion phase where 24 patients will be treated at the highest dose twice a day for 6 months.

Pharmaxis CEO Gary Phillips said, "We are very pleased to have completed the dose escalation phase of this study with such clear and positive findings.We will now immediately progress to the phase 2 dose expansion study where we aim to show PXS-5505 is safe to be taken longer term with the disease modifying effects that we have seen in the pre-clinical models. The trial infrastructure and funding is in place and we are on track to complete the study by the end of 2022."

Independent, peer-reviewed research has demonstrated the upregulation of several lysyl oxidase family members in myelofibrosis.The level of inhibition of LOX achieved in the current study at all three doses significantly exceeds levels that caused disease modifying effects with PXS-5505 in pre-clinical models of myelofibrosis with improvements in blood cell count, diminished spleen size and reduced bone marrow fibrosis. LOXL2 was inhibited to a similar degree and based on pre-clinical work such high inhibition is likely replicated for other LOX family members (LOXL1, 3 and 4).[1] Study data can be viewed in the full announcement.

Commenting on the results of the trial, Dr Gabriela Hobbs, Assistant Professor, Medicine, Harvard Medical School & Clinical Director, Leukaemia, Massachusetts General Hospital said, "Despite improvements in the treatment of myelofibrosis, the only curative therapy remains an allogeneic stem cell transplantation, a therapy that many patients are not eligible for due to its morbidity and mortality. None of the drugs approved to date consistently or meaningfully alter the fibrosis that defines this disease. PXS-5505 has a novel mechanism of action by fully inhibiting all LOX enzymes. An attractive aspect of this drug is that so far in healthy controls and in this phase 1c study in myelofibrosis patients, the drug appears to be very well tolerated. This is meaningful as approved drugs and those that are undergoing study, are associated with abnormal low blood cell counts. Preliminary data thus far, demonstrate that PXS-5505 leads to a dramatic, >90% inhibition of LOX and LOXL2 at one week and 28 days. This confirms what's been shown in healthy controls as well as mouse models, that this drug can inhibit the LOX enzymes in patients. Inhibiting these enzymes is a novel approach to the treatment of myelofibrosis by preventing the deposition of fibrosis and ultimately reversing the fibrosis that characterizes this disease."

The phase 1c/2a trial MF-101 cleared by the FDA under the Investigational New Drug (IND) scheme aims to demonstrate that PXS-5505, the lead asset in Pharmaxis' drug discovery pipeline, is safe and effective as a monotherapy in myelofibrosis patients who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs. Trial sites will now open to recruit myelofibrosis patients into the 6-month phase 2 study in Australia, South Korea, Taiwan and the USA.

An effective pan-LOX inhibitor for myelofibrosis would open a market that is conservatively estimated at US$1 billion per annum.

While Pharmaxis' primary focus is the development of PXS-5505 for myelofibrosis, the drug also has potential in several other cancers including liver and pancreatic cancer where it aims to breakdown the fibrotic tissue in the tumour and enhance the effect of chemotherapy treatment.

Trial Design

Name of trial

PXS5505-MF-101: A phase 1/2a study to evaluate safety, pharmacokinetic and pharmacodynamic dose escalation and expansion study of PXS-5505 in patients with primary, post-polycythaemia vera or post-essential thrombocythemia myelofibrosis

Trial number

NCT04676529

Primary endpoint

To determine the safety of PXS-5505 in patients with myelofibrosis

Secondary endpoints

Blinding status

Open label

Placebo controlled

No

Trial design

Randomised, multicentre, 4 week duration phase 1 (dose escalation) followed by 6 month phase 2 (dose expansion)

Treatment route

Oral

Treatment frequency

Twice daily

Dose level

Dose escalation: three escalating doses

Dose expansion: one dose

Number of subjects

Dose escalation: minimum of three patients to maximum of 18 patients

Dose expansion: 24 patients

Subject selection criteria

Patients with primary or secondary myelofibrosis who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs

Trial locations

Dose escalation: Australia (2 sites) and South Korea (4 sites)

Dose expansion: Australia, Korea, Taiwan, USA

Commercial partners involved

No commercial partner

Reference: (1) doi.org/10.1002/ajh.23409

AUTHORISED FOR RELEASE TO ASX BY:

Pharmaxis Ltd Disclosure Committee. Contact: David McGarvey, Chief Financial Officer and Company Secretary: T +61 2 9454 7203, E david.mcgarvey@pharmaxis.com.au

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About Pharmaxis

Pharmaxis Ltd is an Australian clinical stage drug development company developing drugs for inflammatory and fibrotic diseases, with a focus on myelofibrosis. The company has a highly productive drug discovery engine built on its expertise in the chemistry of amine oxidase inhibitors, with drug candidates in clinical trials. Pharmaxis has also developed two respiratory products which are approved and supplied in global markets, generating ongoing revenue.

Pharmaxis is developing its drug PXS-5505 for the bone marrow cancer myelofibrosis which causes a build up of scar tissue that leads to loss of production of red and white blood cells and platelets. The US Food and Drug Administration has granted Orphan Drug Designation to PXS-5055 for the treatment of myelofibrosis and permission under an Investigational Drug Application (IND) to progress a phase 1c/2 clinical trial that began recruitment in Q1 2021. PXS5505 is also being investigated as a potential treatment for other cancers such as liver and pancreatic cancer.

Other drug candidates being developed from Pharmaxis' amine oxidase chemistry platform are targeting fibrotic diseases such as kidney fibrosis, NASH, pulmonary fibrosis and cardiac fibrosis; fibrotic scarring from burns and other trauma; and inflammatory diseases such as Duchenne Muscular Dystrophy.

Pharmaxis has developed two products from its proprietary spray drying technology that are manufactured and exported from its Sydney facility; Bronchitol for cystic fibrosis, which is approved and marketed in the United States, Europe, Russia and Australia; and Aridol for the assessment of asthma, which is approved and marketed in the United States, Europe, Australia and Asia.

Pharmaxis is listed on the Australian Securities Exchange (PXS). Its head office, manufacturing and research facilities are in Sydney, Australia. http://www.pharmaxis.com.au

About PXS-5505

PXS-5505 is an orally taken drug that inhibits the lysyl oxidase family of enzymes, two members LOX and LOXL2 are strongly upregulated in human myelofibrosis. In pre-clinical models of myelofibrosis PXS-5505 reversed the bone marrow fibrosis that drives morbidity and mortality in myelofibrosis and reduced many of the abnormalities associated with this disease. It has already received IND approval and Orphan Drug Designation from the FDA.

Myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure. Under normal conditions, the bone marrow provides a fine network of fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres.

In myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over-stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow for example in the spleen and liver, which become enlarged as a result.

Myelofibrosis can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of myelofibrosis remains largely unknown. It can be classified as either JAK2 mutation positive (having the JAK2 mutation) or negative (not having the JAK2 mutation).

Source: Australian Leukemia Foundation: https://www.leukaemia.org.au/disease-information/myeloproliferative-disorders/types-of-mpn/primary-myelofibrosis/

Forward-looking statements

Forwardlooking statements in this media release include statements regarding our expectations, beliefs, hopes, goals, intentions, initiatives or strategies, including statements regarding the potential of products and drug candidates. All forward-looking statements included in this media release are based upon information available to us as of the date hereof. Actual results, performance or achievements could be significantly different from those expressed in, or implied by, these forward-looking statements. These forward-looking statements are not guarantees or predictions of future results, levels of performance, and involve known and unknown risks, uncertainties and other factors, many of which are beyond our control, and which may cause actual results to differ materially from those expressed in the statements contained in this document. For example, despite our efforts there is no certainty that we will be successful in developing or partnering any of the products in our pipeline on commercially acceptable terms, in a timely fashion or at all. Except as required by law we undertake no obligation to update these forward-looking statements as a result of new information, future events or otherwise.

CONTACT:

Media: Felicity Moffatt: T +61 418 677 701, E felicity.moffatt@pharmaxis.com.au

Investor relations:Rudi Michelson (Monsoon Communications) T +61 411 402 737, E rudim@monsoon.com.au

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Pharmaxis Cleared To Progress To Phase 2 Bone Marrow Cancer Trial - WAGM

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Shahid Akhter, editor, ETHealthworld spoke to Dr. Dinesh Bhurani, Director, Department of Hemato-Oncology & Bone Marrow Transplant, Rajiv Gandhi Cancer Institute and Research Centre, to know about the progress of NPRD and the challenges associated with blood stem cell transplants.

How do you think the National Policy for Rare Diseases will impact the treatment of patients suffering from rare blood disorders? Will it help reduce the lag that we often see in policy and practice when it comes to healthcare systems?National Policy on Rare Diseases is a step-in right direction and must be welcomed by the Indian medical fraternity. It not only recognizes rare diseases for the first time in India but also has brought forward the possibility of affordable treatment for life-threatening rare diseases which were not previously covered under the national health program. The policy advocates access for treatment through center of excellences, crowd funding and financial assistance.

The NPRD in a bid to enable patients suffering from rare blood disorders has laid emphasis on the option of one-time curative treatment through hematopoietic stem cell transplant for diseases such as Severe Combined Immunodeficiency (SCID), Chronic Granulomatous disease, Wiskott Aldrich Syndrome, Osteopetrosis, and Fanconi Anaemia. By committing to provide a Rs. 20 lakhs cover for the one-time treatment cost of diseases falling under Group 1 through the umbrella scheme of Rashtriya Arogya Nidhi, the NPRD has attempted to provide coverage to almost 40 per cent of the population who are eligible under the Pradhan Mantri Jan Arogya Yojana. The NPRD as a policy that advocates affordable and accessible healthcare and has the potential to lead to the creation of a conducive healthcare ecosystem whereby multisectoral partnerships can collaboratively work towards reduction in the lag between policy and practice often seen otherwise, thereby leading people to live healthier and fuller lives.

Another reason for low number of donors in India is the misconception that stem cell donation comes with a cost to donor. This idea is completely misplaced and untrue as the cost of procedure starting from sample collection, donation and travel is free of cost, and covered under the cost of treatment of a patient for whom the donation is needed. Added to this is the fact that the number of organizations working in the country in the space of blood stem cell transplant is limited at best, thus awareness generation as compared to other health issues is nominal. However, the situation is gradually evolving and ICMR in its 2021 guidelines has gone on to recognize seven registries across the country as active stakeholders in this ecosystem. This recognition by ICMR will hopefully lead to greater awareness generation.

For blood stem cell transplant knowledge is key in establishing patient donor linkage, and by storing the requisite information with them, these registries do just that. Technology is a tool that has been successfully leveraged by stakeholders in the ecosystem to establish linkages. The Hap- E Search is one such tool that has been used by hospitals in the country to find donor matches for their patients. This software is perhaps one of the most enabling tools available to us in the ecosystem, as it helps find HLA matches not just in the country but across the world. This software is now being used by many government hospitals like AIIMS, Delhi and PGIMER Chandigarh. Once the matching donor is found via the HAP-E Search, the donor is encouraged to make the donation, provided counselling and support to donate blood stem cells, and post donation the stem cells are transported to the patients location.

The NPRD proposed crowdfunding and PPP models to ensure more patients availing treatment for rare diseases. How beneficial do you think such partnerships can be to enable blood stem cell transplant ecosystem?Treatment for rare diseases has been found to be expensive across the world. It is thus that despite stem cell transplants being a proven effective solution in the case of some blood disorders, affordability continues to be a challenge for patients and their families. With treatment costs ranging anywhere between Rs. 15-45 lakh, it remains out of reach for most patients in the country. Also, blood disorders, classified as rare, have limited infrastructure in health systems, networks, and subsidies for patients to access treatments are few. In such a scenario, crowdfunding is definitely a feasible option for patients that would ensure that they do not have to forego treatment due to a paucity of resources.

As per the NPRD, the money raised through crowdfunding would directly get credited to the treatment centre thus ensuring that there is adequate linkage. Further, the public private partnership model suggested by the government has enabled it to avail the support of non- governmental and not-for- profit agencies present in the country. This is truly commendable as not only will this ensure more patient donor linkage in the blood stem transplant ecosystem but will also lead to greater awareness generation and registrations of donors as well. One significant organization that has already partnered with the government in this arena is the DKMS BMST Foundation India. With over 50,000 blood stem cell donors registered with them, this organization has been steadily working towards enabling the ecosystem. In the case of rare diseases, it is imperative that stakeholders do not work in isolation and the government working alongside the private can lead to greater hope for many patients with greater amenities and facilities for treatment being made accessible to them.

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Lack of awareness about blood stem cell donation is one of the leading causes for low number of donors in In.. - ETHealthworld.com

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DBMR has added another report named Exosome therapeutic Market with information Tables for recorded and figure years addressed with Chats and Graphs spread through Pages with straightforward definite examination. The a-list report concentrates on broad assessment of the market development expectations and limitations. The systems range from new item dispatches, extensions, arrangements, joint endeavors, organizations, to acquisitions. This report includes profound information and data on what the markets definition, characterizations, applications, and commitment and furthermore clarifies the drivers and restrictions of the market which is gotten from SWOT investigation. Worldwide market examination report serves a great deal for the business and presents with answer for the hardest business questions. While making Exosome therapeutic Market report, examination and investigation has been completed with one stage or the mix of a few stages relying on the business and customer necessities.

Market definition canvassed in the predominant Exosome therapeutic Market advertising report investigates the market drivers that show factors causing ascend in the market development and market limitations which demonstrate the components causing fall in the market development. It helps clients or other market members to know about the issues they might confront while working in this market throughout a more extended timeframe. This statistical surveying report additionally concentrates on utilization of market, central participants included, deals, value, income and portion of the overall industry with volume and an incentive for every area. The greatness and straightforwardness proceeded in Exosome therapeutic Market business research report makes acquire the trust and dependence of part organizations and clients.

Global Exosome Therapeutic Market By Type (Natural Exosomes, Hybrid Exosomes), Source (Dendritic Cells, Mesenchymal Stem Cells, Blood, Milk, Body Fluids, Saliva, Urine Others), Therapy (Immunotherapy, Gene Therapy, Chemotherapy), Transporting Capacity (Bio Macromolecules, Small Molecules), Application (Oncology, Neurology, Metabolic Disorders, Cardiac Disorders, Blood Disorders, Inflammatory Disorders, Gynecology Disorders, Organ Transplantation, Others), Route of administration (Oral, Parenteral), End User (Hospitals, Diagnostic Centers, Research & Academic Institutes), Geography (North America, Europe, Asia-Pacific and Latin America)

Market Analysis and Insights:Global Exosome Therapeutic Market

Exosome therapeutic market is expected to gain market growth in the forecast period of 2019 to 2026. Data Bridge Market Research analyses that the market is growing with a CAGR of 21.9% in the forecast period of 2019 to 2026 and expected to reach USD 31,691.52 million by 2026 from USD 6,500.00 million in 2018. Increasing prevalence of lyme disease, chronic inflammation, autoimmune disease and other chronic degenerative diseases are the factors for the market growth.

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Exosomes are used to transfer RNA, DNA, and proteins to other cells in the body by making alteration in the function of the target cells. Increasing research activities in exosome therapeutic is augmenting the market growth as demand for exosome therapeutic has increased among healthcare professionals.

Increased number of exosome therapeutics as compared to the past few years will accelerate the market growth. Companies are receiving funding for exosome therapeutic research and clinical trials. For instance, In September 2018, EXOCOBIO has raised USD 27 million in its series B funding. The company has raised USD 46 million as series a funding in April 2017. The series B funding will help the company to set up GMP-compliant exosome industrial facilities to enhance production of exosomes to commercialize in cosmetics and pharmaceutical industry.

Increasing demand for anti-aging therapies will also drive the market. Unmet medical needs such as very few therapeutic are approved by the regulatory authority for the treatment in comparison to the demand in global exosome therapeutics market will hamper the market growth market. Availability of various exosome isolation and purification techniques is further creates new opportunities for exosome therapeutics as they will help company in isolation and purification of exosomes from dendritic cells, mesenchymal stem cells, blood, milk, body fluids, saliva, and urine and from others sources. Such policies support exosome therapeutic market growth in the forecast period to 2019-2026.

This exosome therapeutic market report provides details of market share, new developments, and product pipeline analysis, impact of domestic and localised market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, product approvals, strategic decisions, product launches, geographic expansions, and technological innovations in the market. To understand the analysis and the market scenario contact us for anAnalyst Brief, our team will help you create a revenue impact solution to achieve your desired goal.

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Competitive Landscape and Exosome Therapeutic Market Share Analysis

Global exosome therapeutic market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, company strengths and weaknesses, product launch, product trials pipelines, concept cars, product approvals, patents, product width and breadth, application dominance, technology lifeline curve. The above data points provided are only related to the companys focus related to global exosome therapeutic market.

The major players covered in the report are evox THERAPEUTICS, EXOCOBIO, Exopharm, AEGLE Therapeutics, United Therapeutics Corporation, Codiak BioSciences, Jazz Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH, ReNeuron Group plc, Capricor Therapeutics, Avalon Globocare Corp., CREATIVE MEDICAL TECHNOLOGY HOLDINGS INC., Stem Cells Group among other players domestic and global. Exosome therapeutic market share data is available for Global, North America, Europe, Asia-Pacific, and Latin America separately. DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

Many joint ventures and developments are also initiated by the companies worldwide which are also accelerating the global exosome therapeutic market.

For instance,

Partnership, joint ventures and other strategies enhances the company market share with increased coverage and presence. It also provides the benefit for organisation to improve their offering for exosome therapeutics through expanded model range.

Global Exosome Therapeutic Market Scope and Market Size

Global exosome therapeutic market is segmented of the basis of type, source, therapy, transporting capacity, application, route of administration and end user. The growth among segments helps you analyse niche pockets of growth and strategies to approach the market and determine your core application areas and the difference in your target markets.

Based on type, the market is segmented into natural exosomes and hybrid exosomes. Natural exosomes are dominating in the market because natural exosomes are used in various biological and pathological processes as well as natural exosomes has many advantages such as good biocompatibility and reduced clearance rate compare than hybrid exosomes.

Exosome is an extracellular vesicle which is released from cells, particularly from stem cells. Exosome functions as vehicle for particular proteins and genetic information and other cells. Exosome plays a vital role in the rejuvenation and communication of all the cells in our body while not themselves being cells at all. Research has projected that communication between cells is significant in maintenance of healthy cellular terrain. Chronic disease, age, genetic disorders and environmental factors can affect stem cells communication with other cells and can lead to distribution in the healing process. The growth of the global exosome therapeutic market reflects global and country-wide increase in prevalence of autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases, along with increasing demand for anti-aging therapies. Additionally major factors expected to contribute in growth of the global exosome therapeutic market in future are emerging therapeutic value of exosome, availability of various exosome isolation and purification techniques, technological advancements in exosome and rising healthcare infrastructure.

Rising demand of exosome therapeutic across the globe as exosome therapeutic is expected to be one of the most prominent therapies for autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases treatment, according to clinical researches exosomes help to processes regulation within the body during treatment of autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases. This factor has increased the research activities in exosome therapeutic development around the world for exosome therapeutic. Hence, this factor is leading the clinician and researches to shift towards exosome therapeutic. In the current scenario the exosome therapeutic are highly used in treatment of autoimmune disease, chronic inflammation, Lyme disease and chronic degenerative diseases and as anti-aging therapy as it Exosomes has proliferation of fibroblast cells which is significant in maintenance of skin elasticity and strength.

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Exosome therapeutic Market Country Level Analysis

The global exosome therapeutic market is analysed and market size information is provided by country by type, source, therapy, transporting capacity, application, route of administration and end user as referenced above.

The countries covered in the exosome therapeutic market report are U.S. and Mexico in North America, Turkey in Europe, South Korea, Australia, Hong Kong in the Asia-Pacific, Argentina, Colombia, Peru, Chile, Ecuador, Venezuela, Panama, Dominican Republic, El Salvador, Paraguay, Costa Rica, Puerto Rico, Nicaragua, Uruguay as part of Latin America.

Country Level Analysis, By Type

North America dominates the exosome therapeutic market as the U.S. is leader in exosome therapeutic manufacturing as well as research activities required for exosome therapeutics. At present time Stem Cells Group holding shares around 60.00%. In addition global exosomes therapeutics manufacturers like EXOCOBIO, evox THERAPEUTICS and others are intensifying their efforts in China. The Europe region is expected to grow with the highest growth rate in the forecast period of 2019 to 2026 because of increasing research activities in exosome therapeutic by population.

The country section of the report also provides individual market impacting factors and changes in regulation in the market domestically that impacts the current and future trends of the market. Data points such as new sales, replacement sales, country demographics, regulatory acts and import-export tariffs are some of the major pointers used to forecast the market scenario for individual countries. Also, presence and availability of global brands and their challenges faced due to large or scarce competition from local and domestic brands, impact of sales channels are considered while providing forecast analysis of the country data.

Huge Investment by Automakers for Exosome Therapeutics and New Technology Penetration

Global exosome therapeutic market also provides you with detailed market analysis for every country growth in pharma industry with exosome therapeutic sales, impact of technological development in exosome therapeutic and changes in regulatory scenarios with their support for the exosome therapeutic market. The data is available for historic period 2010 to 2017.

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Exosome therapeutic Market Report- Trends Key Programs Analysis and Competitive Landscape and Forecast 2028 Amite Tangy Digest - Amite Tangy Digest

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Trained as a chemist, biophysicist, internist, and cardiologist, Mark Yeager is eager to propel the Frost Institute for Chemistry and Molecular Science into a leading research center.

Even in his youth Mark Yeager could picture the door to his future. Scuffed, chipped, and almost black from layers of varnish, the old, wooden door had a frosted window with five words stenciled in glossy black: Laboratory of Dr. Mark Yeager.

Yet Yeager, the inaugural executive director of the University of Miamis Frost Institute for Chemistry and Molecular Science (FICMS), is quite happy that his new lab in the 94,000-square-foot building slated to open late next year wont even have a door. The $60 million facilitys open floor plan was designed to encourage the free flow of people and ideasand help transform the University into one of the worlds premier research centers for improving the health of humans and that of our planet.

That is the vision, but its not a fantastical vision, said Yeager, a distinguished biophysicist and cardiologist whose top priority is attracting a diverse and elite group of scientists as the institutes first faculty. It is achievable, and it will happen because the University has not wavered in its commitment to elevate STEM (science, technology, engineering, and mathematics) to advance scientific discovery. Theres something going on here thats organic and alive and excitingand Im thrilled to be part of it.

Yeager, whose own groundbreaking research focuses on the molecular causes of heart disease and viral infections, trained as a chemist at Carnegie-Mellon University, as a physician and biophysicist at Yale University and as an internist and cardiologist at Stanford University. He spent two decades at Scripps Research in California, where he established his first independent laboratory, served as the director of research in cardiology, and helped launch the Skaggs Clinical Scholars Program in Translational Research. He has also served as a consultant and scientific and clinical advisor to several biotech companies.

Now he is transitioning to the University from the University of Virginia School of Medicine (UVA), where he chaired the Department of Molecular Biophysics and Biochemistry for nearly a dozen years and helped establish the Sheridan G. Snyder Translational Research Building. At UVA, he also established one of the nations five regional centers for cryo-electron microscopy (cryoEM)the technique he advanced for flash-freezing, imaging, and studying proteins and other macromolecules in their near-natural state.

It is exciting to see the progress being made on the evolution of our Frost Institutes, starting with Data Science and Computing and now the emergence of Chemistry and Molecular Science. We are fortunate to have Mark overseeing our Frost Institute for Chemistry and Molecular Science and working across the entire institutionhis interdisciplinary knowledge and perspective on chemistry are essential for our success, said Jeffrey Duerk, executive vice president for academic affairs and provost. Mark brings a wealth of knowledge and experience to the University of Miami and we are looking forward to his impactful leadership continuing as we move forward.

Yeager said he knew he was making the right career move on his first visit to the University last November. Although the COVID-19 pandemic had curtailed in-person learning and suspended new construction, he heard the unmistakable sound of heavy equipment as he walked past the royal palms and fountain at the end of Memorial Drive, where the five-story FICMS now stands.

I could see an excavation area and heard a cacophony of construction noise where I had a hunch the institute should be, he recalled. That told me that the University was all in. They had made this commitment to fortify STEM and to do transformational science and nothing was going to stop them. In spite of the pandemic, it was all systems go.

The Universitys longtime benefactors, Phillip and Patricia Frost, enabled that commitment in 2017, when they announced their landmark $100 million gift to establish the Frost Institutes for Science and Engineering, now a key initiative of the Roadmap to Our New Centurythe strategic plan guiding the University toward its centennial mark. The umbrella organization for a group of multidisciplinary research centers patterned after the National Institutes of Health and its network of affiliated institutes, the Frost Institutes were envisioned to translate interdisciplinary research into solutions for real-world problems.

Though Yeager officially started his new role on June 1, he has been heavily involved in planning the FICMS' interior for months. He recently placed a $20 million order to equip the facility with five different electron microscopy instruments that chemists, molecular scientists, and engineers will use to explore the molecular structure of exquisitely beam-sensitive soft materials like proteins, hard materials such as metal alloys, as well as nanomaterials comprised of soft and hard components. Along with the buildings state-of-the-art technology and the Universitys research infrastructure, hes confident its location in the heart of the Coral Gables campus will help him recruit a diverse and elite group of scientists who are exploring challenging avenues of impactful researchsomething he has been driven to do almost his entire life.

An occasional songwriter, guitar player, and jogger who in his younger days ran 18 marathons, Yeager was always fascinated by scientific discoveries that illuminated unknown and unseen worlds. A child of the Sputnik era who began entering science fairs in junior high, he began forging his own career as a physician-scientist while in high school in Colorado Springs, Colorado, where his father, an agricultural economist, settled his family after a number of job-related moves.

Inspired by an experiment in Scientific American magazine, he convinced physicians in the therapeutic radiology department at Penrose Hospital to irradiate his fruit flies so he could compare the effects of administering different doses of radiation on their eye pigments. Delivered in Styrofoam cups, his experiments on what is now called dose fractionationand used to reduce tissue damage during cancer treatmentswon him first place in the U.S. Department of Agricultures 1967 International Science Fair and a research stint in an insect toxicology lab in Berkeley, California.

The following summer, when Yeager returned to Penrose Hospital to work as an orderly, he realized that he loved patient care as much as laboratory research and began plotting how he could pursue both careers.

I just got incredible satisfaction from helping patients get out of bed and into a wheelchair, transfer to a gurney, learn to use crutches, recalled Yeager, who joins the University as one of its 100 Talents for 100 Years, a Roadmap initiative to add 100 new endowed chairs to the faculty by the Universitys 2025 centennial. But I also loved chemistry. I loved physics. I loved too many things.

After earning his undergraduate degree in chemistry from Carnegie-Mellon, he was accepted to the Medical Scientist Training Program at Yale University, where, along with his medical degree, he earned his masters degree and doctorate in molecular biophysics and biochemistry. There, he encountered the first of many trailblazing scientists, including two future Nobel laureates, who would influence his lifes work. His Ph.D. advisor, Lubert Stryer, was particularly influential. Stryer authored a premier textbook of biochemistry, pioneered fluorescence-based techniques to explore the motions of biological macromolecules, and made fundamental discoveries on the molecular basis of vision. Yeagers graduate work on rhodopsin, a photoreceptor membrane protein, triggered his fascination with elucidating the molecular bases for such diseases as sudden cardiac death, heart attacks, HIV-1, and other viral infections.

Yeager completed his medical residency and specialized fellowship training in cardiovascular medicine at Stanford University Medical Center, where he managed the pre- and post-operative care of heart transplant patients and wrote 13 chapters in the book Handbook of Difficult Diagnoses.

He also continued exploring cellular biology in the laboratory of Nigel Unwin, who had collaborated with future Nobel laureate Richard Henderson to pioneer the use of cryoEM to determine the molecular structure of membrane proteinsand inspired Yeagers groundbreaking research on gap junction channels. The electrical conduits that connect every cell in the body to its neighbor, gap junction channels play a critical role in maintaining the normal heartbeat.

That research, which Yeager continued at Scripps and at UVA, explained how gap junction channels behave in their normal state, and during an injured state, such as a heart attack. His quest to answer another question particularly relevant todayhow viruses enter host cells, replicate, and assemble infectious particlesis exemplified by his breakthrough research on the assembly, structure, and maturation of HIV-1, the virus that causes AIDS.

Today, those insights, which Yeager humbly calls a few bricks in the edifice of science, hold important clues for developing new, more effective therapies to prevent HIV-1 infection, repair injured tissue, and treat cancer and cardiovascular diseasethe kind of impactful research that the FICMS was designed to advance with collaborative partners across the University, and beyond.

As a pioneer in the field of cryo-transmission electron microscopy, a forefront technology in materials and biological research, Marks expertise and knowledge will position the University as aleader in these cutting-edge fields, said Leonidas Bachas, dean of the College of Arts and Sciences who served as the initial interim director of the FICMS. We look forward to having him lead the Frost Institute for Chemistry and Molecular Science as we continue to advance the sciences, innovate, and expand research collaborations with our faculty and industry partners.

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Distinguished physician-scientist takes the helm of first Frost Institute - University of Miami

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Everyone has 23 pairs of chromosomes, which include 22 pairs of autosomes and one pair of sex chromosomes. The science that relates to the study of these chromosomes is referred to as cytogenetics. Trained cytogeneticists examine the number, shape, and staining pattern of these structures using special technologies. In this way, they can detect extra chromosomes, missing chromosomes, missing or extra pieces of chromosomes, or rearranged chromosomes.

Chromosome Analysis (Karyotyping)

Karyotyping begins with placing cells on glass slides and separating whole chromosomes from thenucleiof the cells. The slides are stained with special dyes and examined under a microscope. Then, pictures are taken of the chromosomes on the slides, and the picture is cut into pieces, so the chromosome pairs can be arranged and matched. Each chromosome pair is assigned a special number (from 1 to 22, then X and Y) that is based on its staining pattern and size.

Examining a persons whole chromosomes, called karyotyping, can diagnose a wide array of disorders.Down syndrome, in which an individual has an extra chromosome 21, can be determined by karyotyping studies. When there are three chromosomes in one group instead of a pair, it is referred to as a trisomy. Missing chromosomes can also be detected, as in the case ofTurner syndrome, in which a female has only a single X chromosome. When there is only one chromosome instead of a pair, it is referred to as a monosomy.

Sometimes, a piece of a chromosome will break off and attach to another chromosome. When this happens, it is referred to as a translocation or rearrangement. For example,chronic myelogenous leukemia (CML)is a disease caused by a translocation in which a part of chromosome 9 breaks off and attaches itself to chromosome 22 (BCRABL-1 fusion gene). Another example is Burkitt lymphoma, in which a piece of chromosome 8 attaches to chromosome 14. These chromosomal translocations cause disease because the broken piece usually attaches to the new chromosome near a special gene that then becomes activated and helps to produce tumor cells. Translocations can sometimes be seen under the microscope if a special stain is used via karyotyping.

Fluorescence in situ hybridization (FISH)

A special technique commonly called FISH for short can be used to view changes in chromosomes that result from genetic variations. A gene segment in a chromosome can be made to light up or fluoresce when it is bound by a special probe. By using more than one probe at once, cytogeneticists can compare to see if the probes are located in their normal positions or if they have moved to a new location on a different chromosome, or if there are more or fewer copies of a probe than in a normal cell.

Genetic changes in some cancers can be detected using this method. For instance, FISH is one of the methods used to determine increased copy number (amplification) of the gene ERBB2 (also known asHER2) in breast cancer. There are many other applications of FISH technology as well, such as detecting chromosomal deletions, in which a certain part of a chromosome is completely missing. In this case, the chromosome segment will not fluoresce compared to a normal set of chromosomes.

More here:
Genetic Testing Techniques | Lab Tests Online

Recommendation and review posted by Bethany Smith

Helpful information about DNA TestingDNA 101: What Is DNA?

DNA stands for deoxyribonucleic acid, the name of a chemical chain that carries the genetic information of our parents and their parents, and so on. It contains the information needed to build different types of proteins that control different things in the body.

DNA is extremely complex.The rungs on the chemical chainstructured as a double helixare called base pairs, and theres over 3 billion of them across the 23 chromosome pairs in the nucleus of each cell in the human body (for a total of 6 billion over the 46 chromosomes). These base pairs make up about 20,000-25,000 genes, which instruct cells on how to build at least 90,000 proteins throughout all 30 trillion cells in the human body.

A single chromosome, therefore, contains hundreds to thousands of genes. A single gene can have anything from 27,000 to 2 million base pairs.

Chromosomes come in two types of pairs: autosomes, which are identical, as found in chromosomes 1-22), and allosomes, which can be different (as found in the 23rd pair). Allosomes determinethe organisms sex (everyone has one pair of these, either YX for males or XX for females).

DNA that comes from chromosomes is found in the nucleus of every cell, but this isnt the only type of DNA direct-to-consumer companies can use to identify ancestry. The mitochondria in cells also carry DNA. Unlike most nuclear DNA, mtDNA is passed practically unchanged from mother to child.

A common misconception is that DNA is like a blueprint for a human body. Instead, DNA chains are a coded list that instructs cells on how to build proteins. One of our interviewees, Professor Simon Fisher from the Max Planck Institutes Department Language and Genetics, sent us this handy explanation.

The human genomethe complete set of nuclear DNAis 99.9 percent identical for all humans. Its the 0.1 percentthat contains enough differences to make us into unique individuals. Understanding how information is passed on through genes, how genes instruct proteins, and how proteins translate into specific processes in the human body, can help us know ourselves better.

Scientists have identified that certain proteins are linked to specific conditions, diseases, or health risks. Certain proteins, for example, are responsible for the production of thehormone insulin. Mutations, changes, and variations in the genes that instruct cells to build this protein can cause a variety of disorders.

Different direct-to-consumer DNA companies have developed algorithms based on these variations. None of them analyze a persons entire, complex genome. Instead, they focus on markers or locations on the gene code that have been associated with certain populations or conditions.

Most commercial DNA kits offer two kinds of tests: ancestry and health.

Analyzing DNA is not as easy as reading a history book. Its not even as easy as reading science-heavy articles about the chemical composition of DNA.

In order to determine a persons ancestry, companies offer different types of tests:

Autosomal tests: these tests focus on autosomes 1-22 plus the X chromosome.

Y-DNA tests: these tests focus on the Y chromosome (if male), which is used to trace patrilineal ancestors because its passed practically unchanged from fathers to sons.

mtDNA tests: these tests focus on mitochondrial DNA, which is used to trace matrilineal ancestors because its passed practically unchanged from mothers to their children.

The autosomal DNA passed on by our parents is a mix of their DNA, and their parents DNA, and so on. The amount of ancestors doubles with each previous generation. That means DNA from only the last two hundred years can already be a mixture of 510 people (less if ancestors appear multiple times in a family tree).

Most ancestry testing, however, compares specific DNA markers (alleles) against those of existing, contemporary populations determined to have remained, historically, in the same place for a long time (each companys reference panel). A company like Ancestry, for instance, uses algorithms to find which ethnicity assignments return the highest probability matches.

This statistical matching, however, is limited by the natural genetic mixing that has historically occurred throughout many populations. Europeans, for example, are historically comprised of mixtures of populations from the region now known as Turkey, the ancient Roman Empire, and Northern Africa. Within the last 2,000 years, Britain alone has experienced immigration and genetic mixing from the Romans, various Germanic tribes, and the Middle East.

In a 2015 article, Jonathan Kahn, a law professor at Northeastern University who has written extensively on genomics and race, writesThe estimates provided by diverse commercial enterprises [...] are premised on a notion of static populations that have not migrated or mixed over time. [...But] the idea that there are somehow pure types of African, European, or Asian DNA is a ction [...]

This article in the American Journal of Human Genetics echoes that--[O]nly a small fraction of ancestors are represented by each given genomic segment in an individual, [...] so one can only ever have limited information on the origins of a given individual's ancestors. This is why some experts, like Professor Troy Duster from UC Berkeley, question the usage of admixture percentages, "Heres the problem in a nutshell. In order to have something called 'percent admixture'percent white, percent black, percent whatever, percent Italian, percent Jewishyoud have to have something called one hundred percent.

Direct-to-home DNA testing companies often use the term ethnicity when providing reports and statistical probability breakdowns for ancestry, health, and traits. Their usage of the term, however, varies, and it is often left undefined. AncestryDNAs White Paper, for example, does not define ethnicity in its glossary, but in its usage throughout, the term is synonymous with regions, populations, or even nationalities.

However, some have questioned the wisdom and utility of the term ethnicitya socially constructed concept based on self-identificationwhen discussing a biological component, DNA, especially in health contexts. Part of the difficulty arises from the often-contradictory nature of available definitions and its overlap with other socially-constructed and controversial terms like race.

This is further complicated by the facts that 1. there are no clear-cut ethnicities because most populations in the world are mixed to some degree, 2. socially constructed concepts like ethnicity and race have, historically, resulted in bias and discrimination, and 3. an overlap between modern ethnicity labels might not correspond to historical population names or locations.

DNA can certainly reveal a lot of information about where our genes come from. However, its important to understand that companies are only providing estimates based on DNA similarities to other contemporary populations. When an ancestry report says a person is 2% Scandinavian, it does not mean a specific, unique chunk of their DNA can come only from Scandinavia. Instead, what this percentage means is that certain portions of their genes have been statistically similar to those from contemporary Scandinavian populations.

This is why an individual can take multiple DNA tests from different companies or multiple tests with the same company, and get different results, and why identical twins have also been documented as having received slightly different reports.

The size of the databases also has to be taken into account. As Scientific American explains, several companies use both preexisting datasets as well as some reference populations that they have recruited themselves. ScienceNews.org cites anthropological geneticist Deborah Bolnick, saying, Who the companies say you aredependsin large parton those reference populations, Bolnick says. For instance, you may carry a pattern of SNPs found in people in both southern France and in Italy. If, by chance, the French people a company sampled had that SNP pattern but none of the Italians in the companys database did, they may infer that you have French ancestors and not Italian because of who they do and do not have in their database.

The Genetic Resource Center for the National Congress of American Indians explains the limitations of making probability estimates based on database comparison and the problem of using this to identify certain ethnic groups. [T]hese results are limited by the information in current databases, many of which do not contain a lot of information for particular groups (AI/ANs among them). This limitation in the data can produce problems for tribes and individuals seeking information as results may not be accurate or even possible to generate given limited availability of comparative data.

Companies like HomeDNA and African Ancestry are currently trying to address some of these limitations for African and Asian populations. As ScienceNews.org comments, some groups, including aboriginal populations in Australia and big parts of Africa and Asia, are mostly absent from companies databases.

Y-DNA and mtDNA are currently the most authentic and useful tests for ancestry, according to Dr. Troy Duster, professor of sociology at UC Berkeley. They are, as he told us, definitive and replicable. However, research suggests that lineage-based genetic estimates [...] reflect only a fraction of any person's total genetic ancestry.

Y-DNA tests can only trace one patrilineal ancestor at each generation because only one ancestor (a father) passed the Y chromosome to the next (his son). That means that, increasingly, at each further past generation, an individual has more and more ancestors that contributed to their genetic makeup, but which can't be reliably identified by tracing their genes.

Mitochondrial DNA tests are similarly limited; only the mothers mothers mothers mothers (etc.) mitochondrial DNA was passed on, meaning only one line can be traced. The paternal grandmothers line for any individual cannot be traced.

Like with ancestry testing, interpreting DNA in order to understand an individuals health risks, is a complicated business. Amy Sturm, president of the National Society of Genetic Counselors, explained how genetic analysis takes place."There is a reference for the normal human DNA code and, based on research that has been done looking at people with certain traits or conditions or diseases, we know that there are certain genes, that if they have a change in them a genetic variant that it would be associated with a certain trait or condition or disease. And so, with the DNA being analyzed in the laboratory, the scientists are looking for changes in the normal DNA code that they know is associated with a trait or condition."

She warns, however, that its usually not a simple 1-1 correlation because there are other genetic factors and environmental factors that likely play a role in that complexity, and we dont have all of those even have those figured out yet. Thus, whether a person takes a direct-to-consumer DNA test or a full test with a genetic counselor, its important they understand that it is more of a risk conversation.

The American Journal of Human Genetics highlights that the scientific claims of companies that choose not to disclose the contents of their proprietary databases cannot be assessed; therefore, the reliability of the information they provide to consumers cannot be verified. This is problematic because, as professor Duster told us in our interview, replicability is the key element in scientific study. However, some direct-to-consumer DNA testing companies are not opening this up to investigation by other scientists saying ok, you can come in and look at our data and see if you can do a replication study.

Ruth Saunders, a law graduate from Queen Mary University of London, echoes Dusters concerns in her 2010 article on the legal implications of DTC genetic testing and the lack of regulatory agencies enforcing scientific validity:The lack of regulation governing the quality of the genetic testing services is a serious concern because a genetic test is only useful to health when its analytical and clinical validity and clinical utility is assured.

Moreover, consumers should be aware that false-positive results can and do occur.

Commercial DNA testing companies often promote themselves through commercials that feature customers with uplifting stories and extremely happy results. Unexpected positive results are certainly one of the biggest draws of this industry, but its important to remember that they are not necessarily the norm.

One common thread across all of our interviewees was that it took a while for the interesting results to come up.

[At first], we just had the estimate genetics. And it was just like that for a while. And every once in a while, somebody would pop up, and it was a cousin that everybody knew, said Erin Dull, who found her half-sister through AncestryDNA.

Adam Lind, one of our employees, similarly described his own experience with AncestryDNA:

I got my results back at the beginning of March 2018. And at first, I was like, 0 for 1 there was no Native American, which is what I wanted to know. But there was a lot of UK DNA, like Irish and I didnt know that the Irish, specifically but there was English, Scottish, and some Western European. And I knew that I had a grandfather from Belgium. So, everything seemed copacetic.

Amy Sturm, president of the NSGC, gave us the following advice regarding managing expectations:

"There are many things people need to think about. You might learn something that youre not prepared to learn. You need to be prepared for this going in. You need to think through for yourself Am I the type of person that would prefer ignorance is bliss? Do I really not want to have family secrets unraveled or unveiled to me? And if so, you might not want to take one of these tests. It depends on the person. Its just something you really have to think about before you spit in that tube."

We spoke to three people who discovered that they had a half-sister, that their father was not their biological father, and that they were at risk of developing breast cancer. These are life-altering scenarios. That said, all three of our interviewees were happy to be aware of these truths about their DNA.

Erin Dull, who discovered her half-sister through AncestryDNA, told us: My life changed. Its the best thing that ever happened to me. Meeting my niece and nephew and having a sister is the greatest thing that ever happened to me.

Similarly, our colleague Adam describes his experience of finding his biological father positively: Hes as excited to know me as I am him. Theres this feeling of make up for the lost time. Im absolutely elated.

Our colleague Sara Altchule, who tested positive for the BRCA 2 gene mutation associated with breast cancer, said to us that, although it was a traumatic experience, she considered it to be the best decision I could have ever made. She documented her experience over several blog posts here.

Although we interviewed three people who experienced amazing or life-changing results, ranging from discovering close family members to a high predisposition towards conditions, this is not necessarily the common outcome. For example, another one of our employees who used 23&Me also commented that hed yet to receive any surprising or unexpected results despite having used the service several months ago.

Two common thread we found through our interviews were either the dont open that can of worms warning, or the if the connection is beyond 1st counsin, Im not interested admission. For example, Erin, one of our interviewees, told us of a friend who had used Ancestry to find her dad. Although he was glad to connect with her, some in the extended family were not, essentially saying we dont know you; youre not a part of this family; we dont want to talk about it.

Theres only one member of the family whos interested; the rest dont even want to talk about it. [One even warned] not to open that can of worms.

This warning is often associated with the potential discovery of family secrets or information that can create an "epistemological crisis,"as professor Duster put it. Not all biological parents want to be found, explores this article on the identity impact these tests can have and many are wary of. Indeed, Ancestrys support center has threads on managing surprising family members and regretting using the service.

On the other hand, some matched family might not want to reply or form a relationship because the connection is vague to them. Adam described his own experience:

The only reason I reached out was because it said father. I think, anything above 'first cousin,' and I would eventually reach out, but other than that, Im not interested. Like, someone who has an ancestor that neither of us has ever met? Im not interested. If someone reached out to me, I would email them back, but I had no interest in reaching out to anybody.

Personal identity is a complex concept influenced by many different factors. But concerns have been raised by experts in bioethics, sociology, anthropology, and genetics about the marketing claims of some DNA testing companies. Some ads for testing companies reinforce the link between DNA and identity, writes ScienceNews.org. For example, AncestryDNAs main page claims You could be Irish; 23&Me promises theyll help customers discover what makes you, you; MyHeritage boasts you can discover where you really come from.

Hina Walajahi, from the National Institute of Health, warns:

While this hyperbolic 'it-will-change-your-life' marketing strategy is not unique to DTC genetic ancestry companies, it is distinct in the way it draws upon public faith in science and scientific authority to validate a causal relationship between genetic ancestry and personal identity.

Prof. Duster explores the powerful draw of these claims:

People have a thirst to believe; theres a real desire to know ones ancestry. For example, because of the history of slavery and because their history was erased, many African Americans in particular have a strong interest in tracing their ancestry back to Africa, in ways people from Europe dont quite have that because they had grandmothers and grandfathers to tell tales about what percent ancestry there is and so on."

But some people are anxious and thirsty for this kind of information, so theyre inclined to believe it as true because thats what they want to believe. This can lead to epistemological crises about who they are.

These crises are not uncommon, as this testimony demonstrates. However, some, like Prof. Duster, challenge placing nature (DNA) above nurture, arguing that:

This notion that, somehow, the DNA that you discover your 'real' biological mother or father is who you really are is an extraordinary leap away from the idea that you are, in part, the social networks that brought you up and that are around you.

Our CEO, Greg Powel, puts it best:

"I think the notion of your self-conception evolves over the course of your life. Youre shaped by a combination of your experiences and the people around you and your genetic make-up and who you are. I think thats who we are as people."

As Amy Sturm from the National Society of Genetic Counselors wisely told us: DNA is not destiny.

Most major direct-to-consumer DNA testing companies have clauses in their Privacy Terms intended to assure customers that their genetic data will not be shared or sold without their consent. In an effort to ensure this, these companies anonymize customers DNA samples, removing identifiable information like name and address when the sample is sent to the lab.

However, experts warn that genomic data is highly distinguishable, and that even a sequence of 30 to 80 SNPs [single-nucleotide polymorphisms, a.k.a. markers or variations] could uniquely identify an individual. In other words, anonymized genetic data can be re-identified:

"[A]s demonstrated by multiple recent studies, the risk of re-identification is strongly present. It was shown, in multiple independent studies, that it is possible to learn the identities of people who participate in research studies by matching their data with publicly available data. Fida K. Dankar, et al. in Human Genomics."

In addition, many DNA matching services are unavailable or limited if consumers do not willingly give up some of their privacy. For example, Ancestrys DNA Matches reminds customers that if you choose not to see your DNA matches or be listed as a match, some of the features included in your Ancestry subscription may not be available.

Privacy and data security concerns have been raised by other consumers, the media, politicians, and experts. These range from genetic data being sold or shared with pharmacological companies for the development of pharmaceuticals, to the potential risks of health or life insurance companies obtaining consumers genetic information and using it to raise their premiums or deny them services. This is because genetic data provides sensitive information about genetic conditions and predispositions to certain diseases such as cancer, Alzheimer's, and schizophrenia.

In her article Privacy of Information and DNA Testing Kits,Shanna Mason points that that submitting to genetic tests are not only exposing themselves to the risk of their genetic information getting into the wrong hands, but are also exposing information about shared familial risk. Masons article explores topics like genetic discrimination, and where the HIPAA and GINA privacy laws come into play.

Nonetheless, consumers are responsible for keeping up-to-date with how privacy terms and conditions are changed or modified over time, and continuing to use the services is treated as acceptance of these changes.

Screenshot from 23andme.com's Terms of Service. August 20, 2019.

Screenshot from 23andme.com's Terms of Service. August 20, 2019.

Additional concerns have also been raised concerning several aspects of law enforcement, including, but not limited to, the use of DNA databases to potentially racially profile suspects, the use of DNA databases in forensics, laws that allow police and federal officials to retain DNA samples even from non-charged suspects or acquitted individuals, and the general wide misunderstanding in legal situations of the limits of genomics.

Consumers also should be aware that DNA companies are legally obligated to submit data and documentation if faced with a warrant or subpoena. Moreover, some companies are openly working in tandemwith law enforcement institutions, and there arent any regulations to stop it.

Many direct-to-consumer DNA kits have expiry dates because of the stabilizing solution they contain. This solution or buffer is what prevents bacterial contamination during the shipping process.

Expiry dates are different for different companies, be it because theyre being overly cautious, or because their kits have longer lifespans than others. Of the ones we used with our DNA volunteers, only AncestryDNA did not have a clear expiry date on the kit itself. Those that did had very different dates, even though we requested them all at the same time:

We recommend that customers mail in their DNA samples at least within a year of receiving their kits in the mail.

Read more:
Top 10 DNA Testing of 2021 | ConsumersAdvocate.org

Recommendation and review posted by Bethany Smith

Research of family registries found that individuals with a germline pathogenic ATM variant gene had greater lifetime risk of developing pancreatic cancer than individuals without the gene.

Individuals with a germline pathogenic ATM variant appear to have an increased lifetime risk of developing pancreatic cancer compared with those without the variant, according to findings from a multicohort study of pancreatic cancer family registries published in JAMA Oncology.

Pancreatic cancer cumulative risk for individuals with the germline pathogenic ATM variant was estimated by age increased from 0.08% (95% CI, 0.07%-0.09%) at 30 years to 0.30% (95% CI, 0.25%-0.36%) at 40 years, 1.08% (95% CI, 0.83%-1.33%) at 50 years, 3.03% (95% CI, 2.12%-3.94%) at 60 years, 6.28% (95% CI, 3.90%-8.66%) at 70 years, and 9.53% (95% CI, 5.04%-14.02%) at 80 years.

These findings underscore the need to develop appropriate surveillance and intervention strategies for these individuals at high-risk of developing pancreatic cancer, the investigators wrote.

The study enrolled kindreds who were included in family registries participating in the Pancreatic Cancer Genetic Epidemiology Consortium, which included the National Familial Pancreas Tumor Registry from Johns Hopkins University, the Biospecimen Resource for Pancreas Research from the Mayo Clinic, GI Cancer Genetics from Dana-Farber Cancer Institute, and the Ontario Pancreas Cancer Study from Mount Sinai Hospital, University of Toronto.

In order to be eligible, families were required to have at least 1 member who had been diagnosed pancreatic cancer and 1 family member with a germline ATM pathogenic variant.

Study population included 2227 individuals from 130 families. Notably, 95% of families were white and 49% of patients were women. The patient population had a mean age of 58 years. Of this population, 155 individuals returned a positive test result for an ATM pathogenic variant.

Although an increased prevalence of pancreatic cancer was seen among individuals not carrying the variant compared with untyped individuals, this was due to preferential genetic testing of patients with cancer over cancer-free individuals. Although other pedigree members had a missing pancreatic cancer status and/or age, they were included in order to complete the family structure; this was believed to have had a limited influence on estimated risk.

Within the families included in the study, 217 individuals had pancreatic cancer. Moreover, 78 families had 1 member with the disease, 34 families had 2 members, and 18 families had 3 or more members. Patients were an average of 64 years of age (range, 31-98) upon being diagnosed.

To determine whether there were findings to support penetrance differences between men and women, sex specific penetrance was examined. However, the study model did not appear to be significant ( = 0.12; SE, 0.11; P = .29). Compared with individuals without the ATM variant, the relative risk estimate of pancreatic cancer was 6.5 (95% CI, 4.5-9.5) for individuals with the ATM variant.

Compared with studies that have estimated a 2.2- to 6.6-fold increased risk of pancreatic cancer in BRCA2 variant carriers, the risk estimates of the present study strongly support inclusion of ATM variant carriers in screening trials, the investigators wrote.

The main limitation of the research centered around the European ancestry, which encompassed the majority of families included in the study population. The investigators suggest that future studies focus on non-European populations to better understand the risk of germline ATM variants.

Hsu FC, Roberts NJ, Childs E, et al. Risk of pancreatic cancer among individuals with pathogenic variants in the ATM Gene. JAMA Oncol. Published online September 16, 2021.doi:10.1001/jamaoncol.2021.3701

Read more:
Individuals With Pathogenic ATM Variant Have an Increased Lifetime Risk of Developing Pancreatic Cancer - Cancer Network

Recommendation and review posted by Bethany Smith

Theres growing concern about genetic discrimination in New Zealand and the lack of Government intervention in this fast-moving field.

As genetictesting becomes more accessible than ever before, there are calls for a line in the sand to be drawn and a final answer toaquestionnot yet canvassed: should insurers be able to use our geneticinformation?

Genetic discrimination is using someones genetic information to discriminate against them to treat them in a way thats different to someone else because we know something about their genetics.

Currently,lifeand health insurance companies in New Zealand are allowed to use thisdatain determining coverand premiumsfor applicants something experts sayanecdotalevidence suggest hasledto increased premiums, or no cover at all.

While insurers may argue it's their right to know a person's medical history researchers say genetics is, in fact, not a part of one's history, but a part of their future.

There are a lot of complexities in determining someone's genetic makeup and whether they are prone to getting a disease later in life.

There are also ways to mitigate and change the outcome of a patient's health once becoming privy to this information. For example, getting a mastectomywill drastically limit the chances of getting breast cancer, but there are fears an insurer may refuse cover based on a positive BRCA gene test regardless.

University ofOtago law and bioethics lecturerDr Jeanne Snellingsaysif people do have the test,and its positive, they can do things tominimisedevelopment of the disease.

They can undergo surveillance, get prophylactic preventative treatment and their risk could be quite similar to someone elses in the end. But, the insurance company is taking this absolutist approach saying that a positive test disqualifies you from obtaining life insurance cover.

There aredoubts about whether an insurance company would have staff with the expertise on hand to dissect someones genetic information.

University of Aucklands Faculty of Medical and Health Sciences Professor Andrew Shelling says it usually takes acastofspecialists to trawl through the data of an entire persons genome.

Good luck to the insurance company if they can find something, let us know. Because we have an entire team of experts from the clinicians to thebioinformaticiansto the geneticists who sit in a multi-disciplinary clinic each week trying to discuss the outcomes of what theyre looking at.

Based on the increased complexity of genetic testing nowadays, there is also a risk of getting it wrong if you dont have the right expertise. Hesaid.

There'salsoconcernpeople will not opt for undergoing genetic testing purely based on the fact it could be used by insurers -- and thus, miss out on the opportunity to decreasefuturehealth risks.

Despite the life-saving prevention available through genetic testing, experts say people avoiditand research because they are afraid of insurance discrimination.

This not only limits what a person can do to better their health in future -- but stunts medical research, particularly in minority groups like Mori and Pasifika, whose genetics are an even greater enigma to researchers than Pakeha.

Professor Shelling says we know that Mori have been discriminated against for years and this may be another form of it.

We base a lot of our genetics on European DNA, so for our Mori and Pasific people we dont always know what their results mean in a clinical setting.

We have an extra responsibility as genomic scientists to support Mori and Pasific getting genetic testing and make sure they dont get further discriminated against.

In a lot of our research studies around New Zealand, we are trying to increase the number of Mori and Pasific participants.

He fears if they have any concerns about insurance, theyllturn away from being part of these studies.

It's a conflict Jane Tiller anethical, legal and social advisor for Public Health Genomics at Melbournes Monash University --has battled for five years in Australia where a moratorium's been put in place to try and curb the issue.

Now, in Australia, you can get life insurance up to $500,000. If you try and take out more, you have to then disclose your genetic test results. she said.

She says the moratoriums a good step towards consumer protection but its a fraught approach.

"It goes up to certain financial limits and is only five years. So, we dont know what will happen in 2024 when it ends.

We are still gathering data about how its [the moratorium]working. Were remaining concerned about the lack of Government regulations on this issue.We would like to see a complete ban, like in Canada.

The moratorium isalso self-regulated by the insurance industry.

Self-regulation has been shown to be conflicted and problematic, both in Australia and New Zealand.

Theres very little transparency on how insurance companies use this data.Because this is self-regulated, theres a lot of questions around how decisions are made and what data is relied on.

The newly formed AGenDA (Against Genomic Discrimination Aotearoa) group, is lobbying for Government attention on this issue.

AGenDasmessage is that genetic discrimination is not only aconsumer protection issue, but a human rights issue.

Theysay itsnot just about making sure insurers get the information they need todiscriminate; its about stopping them from discriminatingaltogether. Its about ensuring consumers can make decisions about healthcare and learn empowering information without fear of discrimination for themselves or their family members.

They say thesectorhas come to presume divulgence -- an expectation thats been born of our insurance industry over many years.

The Financial Services Councils Richard Kiplin says its not something companies will ask for but if a client has information, it's only fair that they disclose it.

Within the New Zealand sector organisation by organisation will make their own calls. he said.

Whats important for New Zealand consumers to understand is that this is a complex area, and life companies need to assess risk and theyll do that in an appropriate way.

Genetic testing,at this point of time, is not a standard part of that -- but thats obviously evolving and moving very fast.

I think if people have had a genetic test and have information then they know information that a life and health company would want to understand. And so thats a part of the disclosure process.

Kiplin says hes open to working with researchers and other parties in future to solidify guidelines around genetic testing.

We have a robust committee structure thats been looking at some of these issues and reviewing guidelines.

The sector is never static, theres always stuff you can change and this is one of the big areas of the future.Hesaid.

AGenDAis alsoconcerned at the lack of Government intervention.

The Minister of Commerce and Consumer Affairs David Clark points towards the Ministry of Business, Innovation and Employment's Insurance Law Review.

"Insurer use of genetic testing results is one of many issues raised with MBIE during the course of the review, but it was not highlighted as a significant issue in the submissions (it was mentioned in two out of around 500 submissions received). Hesaid.

Clark mirrors the industrys openness to work with experts to understand the situation better.

Im told, the industryhavepreviously told my officials they are not seeing high levels of genetic testing, but I am open to further briefings on the matter.

The MBIEreview was promptedto ensure New Zealands insurance contract law is facilitating insurance markets that work well and enable individuals and businesses to effectively protect themselves against risk.

In November 2019 the Government agreed tothereform which includesmaking sure insurers ask consumers the right questions, the requirement for policies to be written and presented clearly, strengthening protection for consumers against unfair terms and extending powers to the Financial Markets Authority to monitor and enforce compliance.

Next steps for the review include release of an exposure draft Bill for consultation in late-2021.

Genetic testing has been described asa quantum leap for healthcare. A new kind ofapparatuswe can use to decode our future health.

In July 2021,the World Health Organization (WHO) provided the first global recommendations to help establish human genome editing as a tool for public health, with an emphasis on safety, effectiveness and ethics.

While their concerns are mainly based around the use of genetics to edit our DNA --WHO Director-General,Dr Tedros Adhanom Ghebreyesus, recognisedgenome editing and testing as a potential to advance our ability to treat and cure disease.

"But the full impact will only be realized if we deploy it for the benefit of all people, instead of fueling more health inequity between and within countries,Hesaid.

In September, the WHOrecommended DNA testing as a first-choice screening method for cervical cancer prevention.

It recognised DNA-based testing for human papillomavirus (HPV) has been shown to be more effective than todays commonly used screening methods aimed at detecting and preventing cervical cancer, a major cause of death among women worldwide.

Asgenetictestingbecomesmore mainstream,as the technologies mature,and as testsbecome moreprecise and affordable-- it evolves from being aniche offering tobecomingilluminatedon healthcarescentrestage.

And whilegenetictesting is applauded for its potential to become a part of our everyday health toolbox one question remains:should insurers be able to use our genetic information?

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Genetic discrimination: The next great health battle likely to wash up on NZ shores - Newstalk ZB

Recommendation and review posted by Bethany Smith

Nearly 1 in 5 adults in Georgia battle mental illness each year

SMYRNA, Ga., Oct. 5, 2021 /PRNewswire/ -- Ridgeview Institute is modernizing the standard of care for behavioral health treatment for Georgians in need of mental health and addiction services, thanks to a new partnership with GeneSight.

Ridgeview Institute - Smyrna

The GeneSight test, offered through Myriad Genetics, Inc. (NASDAQ: MYGN), helps clinicians understand how a particular individual may respond to certain medications by analyzing how a person's genes impact how they may break down or respond to medications commonly prescribed to treat depression, anxiety and other psychiatric conditions.

"Making GeneSight available for patients seeking mental health and addiction treatment is a game-changer in behavioral therapy," said Amy Alexander, CEO, Ridgeview Institute. "Every patient's mental health journey is different, which means their treatment plan needs to be, too. Knowing which medication a patient may respond to before they start treatment can help create a customized treatment plan that can increase response, reduce trial and error and minimize side-effects."

According to the latest federal data, nearly one in five adults in Georgia battle mental illness in any given year, with nearly half a million having at least one major depressive episode. According to one study, fewer than 50% of patients with depression respond to their first prescribed medication, and with each failed medication plan, their response to the treatment may decrease.[1] The process of finding the right medications that work is often frustrating, time-consuming and debilitating.

Ridgeview Institute is the only program of its kind in Georgia that has committed to offering the GeneSight test to every patient participating in outpatient services. Ridgeview Institute believes that everyone deserves to know that GeneSight is an option and an additional tool that may help them in their mental health journey.

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More than 1.5 million patients have used GeneSight to shed light on which medications may be better suited to their treatment and answer questions around why previous medications may not have worked.

The value of GeneSight is already being seen at Ridgeview Institute, contributing to a positive increase in patient outcomes. One patient saw results only one week after genetic testing. The patient was having sleep issues and not spending time with family. She was so tired that she slept for 12 hours every night and woke up fatigued, affecting her relationship with her kids and spouse. After using GeneSight, the clinic adjusted medication and reported seeing a noticeable improvement. The patient now stays up later, enjoys time with her family, and does not feel as fatigued. There is also a noticeable change in her appearance, and the patient is more energetic and upbeat.

"Science is used in all other areas of health to guide treatment, including x-rays, MRIs and blood work. It's a natural fit for genetic testing to be used in helping to customize behavioral therapy treatment," said Alexander. "We're excited by the potential this will have in helping even more Georgians get the help they need."

Ridgeview Institute has been Georgia's first choice in mental health and addiction treatment since 1976. Offering a comprehensive array of programs for youth, young adults, adults, and senior adults, the treatment facility also provides specialized programs for women and licensed professionals who need behavioral health and/or addiction intervention. It also offers the Recovery Residence, apartment-style living for those that are participating in PHP programs, which eliminates distance and transportation obstacles in a person's recovery.

Ridgeview Institute offers free assessments and individuals can be admitted directly into the program or referred after an acute inpatient hospitalization. For more information, please call 844-350-8800, 24 hours a day.

About Ridgeview Institute at Smyrna Since 1976, the mission of Ridgeview Institute has been to provide outstanding care, compassionate people, and unparalleled service, offering a full continuum of inpatient and outpatient mental health and substance abuse treatment to patients in Georgia. Since its founding, Ridgeview Institute at Smyrna has supported over 90,000 patients from Georgia and surrounding areas in mental health and substance use recovery. The suburban Atlanta campus offers patients a safe and serene environment and provides specialized, evidence-based behavioral health and substance use disorder treatment. http://www.ridgeviewinstitute.com/smyrna

[1] 1 Rush AJ, et al. 2006 Am J Psychiatry

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Recommendation and review posted by Bethany Smith

By JOYANNA LOVE/ Managing Editor

A breast cancer diagnosis was no surprise for Jeannie Smith.

In fact, she had been expecting it for 13 years, ever since her mother passed away.

My mom passed from breast cancer when she was 45, Smith said. I was 23 when she passed, and she had a very aggressive type of breast cancer.

That was in 2000. Back then, Smith said genetic testing for cancer was not available.

For 13 years, I waited and wondered because in my mind, I knew it wasnt a matter of if, it was a matter of when, Smith said.

She said she lived in fear and did daily self-examinations.

When health insurance companies started covering genetic testing for the BRCA1 mutation linked to breast cancer, Smith had it done.

I felt strongly that my mom had that mutation, so if she had that mutation, then there was a 50% chance that I had that mutation, Smith said.

She was tested in August 2014, which confirmed she had the BRCA1 mutation. Once this was confirmed, Smith began the process to have preventive surgery a double mastectomy. Smith said those with the mutation have an 87% chance of developing breast cancer in their lifetime, compared to the normal population of 11% in their lifetime.

Knowing how she had anticipated being diagnosed with cancer, her husband and family were supportive of the decision.

Three weeks before the surgery, she had a normal mammogram, but she said tumors often do not show up on a typical mammogram for younger women who have dense breasts.

As a part of routine pre-surgery procedures, a breast MRI was done.

When the phone rang soon after, she knew before she answered that it would be the doctor telling her she had cancer.

She was right.

Her children were ages 16, 10 and 9 when she was diagnosed. Smith said she was afraid that her children would have to go through what she had, losing her mom to cancer.

I was bitter, angry, Smith said. Cancer had already taken so much from me.

However, after a few days, she said God gave her peace.

I woke up the morning of the biopsy in total calmness, Smith said.

She took a sheet of scripture verses with her to help.

Throughout her 13 years of wondering, Smith said she was able to be educated and be very proactive about my health because of the American Cancer Society.

Smith was a volunteer with the Relay For Life of Chilton County, prior to becoming a staff member with the organization.

After mom died, I needed to do something to deal with the grief, something to give back or fight back for her make her death mean something, Smith said.

She said she fell in love with Relay for Life. Later, she worked in various positions for ACS moving into management until 2020.

The organization helped her to know her risk factors and keep up with research and know what I needed to do to stay ahead of the game.

There was even a researcher that was funded by the American Cancer Society that discovered the BRCA gene, Smith said.

Smith had the planned surgery, but now she also had to do four rounds of chemotherapy. Smith said because her cancer was in stage one, and she had a mastectomy, she was uncertain they would do chemotherapy. However, she wanted to have it done just to give her the best chance.

I knew I did not want to be facing this later on, Smith said. I wanted to hit it head on while we had the best chance possible of taking care of everything.

She wrote out three pages of reasons why she wanted it, but did not need it because her doctor had already decided chemotherapy would be a good option.

Smith had the surgery to remove her breasts and DIEP reconstructive surgery on the same day.

She explained that this type of reconstructive surgery takes fatty tissue and vessels and veins from your abdomen and use it to make your breast.

At the time there were only about 80 doctors in the U.S. that were able to do that type of surgery I chose that because it meant no implants, and it meant not having to have repeat MRIs every so many years, Smith said.

Since her cancer was estrogen fed, Smith knew she was at a higher risk of ovarian cancer, so she had a hysterotomy.

She now takes an anti-cancer pill that she will have to take for a total of 10 years.

She has also had some skin cancer treated in that time.

Smith said her cancer journey was turned into a blessing.

I am much stronger now than I ever thought I could be, Smith said. I have drawn closer to my Savior, stronger in my faith. I have been given the opportunity, especially when I was with the American Cancer Society to talk with newly diagnosed patients and caregivers. I had been in both of those roles, so I could relate the opportunity to be that voice of hope.

She said the technology and research has come so far from when her mother was diagnosed, and today, a breast cancer diagnosis does not have to be the end.

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Fear turned to peace for breast cancer survivor Jeannie Smith - The Clanton Advertiser - Clanton Advertiser

Recommendation and review posted by Bethany Smith

An influential Genetic Testing market research report is very indispensable in many ways for business growth and to thrive in the market. This market report looks over the market with respect to general market conditions, market improvement, market scenarios, key developments, cost and profit of the specified market regions, brand position and comparative pricing between major players. In addition, businesses can be well acquainted with the level of the marketing problems, reasons for failure of particular product already existing in the market, and prospective market for a new product to be launched. This report offers a clear understanding of the present as well as future scenario of the Genetic Testing industry. Research techniques like PESTLE and Porters Five Forces analysis have been deployed by the researchers. To understand the market in depth, market research report is the perfect solution. Genetic Testing market document is right there for the same which lets know that how the market is going to perform in the forecast years by giving information about market definition, classifications, applications, and engagements.

Genetic testing market is expected to gain market growth in the forecast period of 2021 to 2028. Data Bridge Market Research analyses the market to reach at an estimated value of 585.81 billion and grow at a CAGR of 11.85% in the above-mentioned forecast period. Increase in incidences of genetic disorders and cancer drives the genetic testing market.

Download Free Exclusive Sample (350 Pages PDF) Report: To Know the Impact of COVID-19 on this Industry @ https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-genetic-testing-market&AS

The Major Players of the Genetic Testing Market Are:

xx

Genetic Testing Market Segmentation:

By Type (Predictive & Presymptomatic Testing, Carrier Testing, Prenatal & Newborn Testing, Diagnostic Testing, Pharmacogenomic Testing, Others)

By Technology (Cytogenetic Testing, Biochemical Testing, and Molecular Testing)

By Application (Cancer Diagnosis, Genetic Disease Diagnosis, Cardiovascular Disease Diagnosis, Others)

By Disease (Alzheimers Disease, Cancer, Cystic Fibrosis, Sickle Cell Anemia, Duchenne Muscular Dystrophy, Thalassemia, Huntingtons Disease, Rare Diseases, Other Diseases)

By Product (Equipment, Consumables)

Read complete report along with TOC @ https://www.databridgemarketresearch.com/toc/?dbmr=global-genetic-testing-market&AS

The Full Report Includes

Enquire for customization in Report @: https://www.databridgemarketresearch.com/inquire-before-buying/?dbmr=global-genetic-testing-market&AS

Key questions answered in the report:

Genetic Testing Market Country Level Analysis

About Data Bridge Market Research Private Ltd:

Data Bridge Market ResearchPvt Ltdis a multinational management consulting firm with offices in India and Canada. As an innovative and neoteric market analysis and advisory company with unmatched durability level and advanced approaches. We are committed to uncover the best consumer prospects and to foster useful knowledge for your company to succeed in the market.

Data Bridge Market Research is a result of sheer wisdom and practice that was conceived and built-in Pune in the year 2015. The company came into existence from the healthcare department with far fewer employees intending to cover the whole market while providing the best class analysis. Later, the company widened its departments, as well as expands their reach by opening a new office in Gurugram location in the year 2018, where a team of highly qualified personnel joins hands for the growth of the company. Even in the tough times of COVID-19 where the Virus slowed down everything around the world, the dedicated Team of Data Bridge Market Research worked round the clock to provide quality and support to our client base, which also tells about the excellence in our sleeve.

Data Bridge Market Research has over 500 analysts working in different industries. We have catered more than 40% of the fortune 500 companies globally and have a network of more than 5000+ clientele around the globe.

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Genetic Testing Market 2021 |Global Industry Analysis By Trends, Size, Share, Company Overview, Growth And Forecast By 2028 The Manomet Current - The...

Recommendation and review posted by Bethany Smith

STRONGSVILLE, Ohio (WJW) Paisley Palmer, 1, dances every morning when she wakes up.

She loves to make people laugh, adores animals and is an expert at blowing kisses.

Her parents say shes an inspiration and a bright light in their lives during a dark time; the active and happy little girl was diagnosed with Acute Myeloid Leukemia in July.

It all started in March, when her mom, Jessica, noticed what looked like a bruise on the right side of her face. She attributed it to the normal bumps toddlers get when theyre active and learning how to walk.

But the mark didnt go away.

It started changing in appearance, said Jessica. It started getting larger, you could actually feel it on the side of her face.

She and her husband, Tim, took Paisley to her pediatrician. After more doctors, ultrasounds and a biopsy, she was diagnosed with AML. Genetic testing also indicated it is a high-risk form of cancer.

Immense shock to us, many emotions during that time, said Jessica. She has never once appeared sickly. Thats really been a bit of a blessing for us. Shes always been so energetic, happy, running around, dancing, making as many friends as she can.

Paisley started treatment at UH Rainbow Babies and Childrens Hospital on Aug. 17. Shes currently on round 2 of what will be four to five rounds of chemotherapy.

After that, because she is high-risk, Paisley will then have to undergo bone marrow transplants. Jessica and Tim were shocked to learn they couldnt be donors. They turned to Be the Match registry for help.

Be The Match, which is operated by the National Marrow Donor Program, plays a role in every bone marrow cell transplant in the United States by matching donors in its registry to patients who need the transplants.

The transplants can be cures for patients like Paisley, who have blood cancers or other diseases or disorders.

Its really wild to me that my husband and I are only a 50 percent match to our little girl, Jessica said. There is a DNA match out there that is better than me and her dad. So we are relying on these good-hearted donors out there that put themselves on the registry and sign up to save a life.

Jessica said Paisleys sample is currently being run through the registry for a match. Jessica says they are hoping for a match to come through as early as the end of this year.

Theyre asking anyone who hears Paisleys story to register to see if they are a match to her or anyone going through blood cancer and other conditions.

Its helping me to see a positive purpose coming out of this devastating news, said Jessica, who has shared their journey to help educate others even more on Instagram. This cancer shows we all really need each other.

Right now, Jessica said Paisley is doing awesome with her treatments and continues to be a bright light for her mom and dad, nurses and doctors.

I am kind of feeding off of her own positivity, and Im happy to be able to share this awareness, said Jessica. Shes giving me the space to do that because shes being so strong herself.

Anyone between the ages of 18 and 40 can join the Be The Match registry by texting SavePaisley to 61474 or by clicking here.

Then, a cheek swab kit will be mailed to their home.

Be The Match covers the cost of transplants, including flights, hotels and meals. It also covers recipient costs that arent covered by insurance.

To find out more about registering or donating, click here.

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All really need each other: Family of 1-year-old Ohio girl with blood cancer waiting for bone marrow donor - WJW FOX 8 News Cleveland

Recommendation and review posted by Bethany Smith

CLN7 program currently in Phase 1 clinical proof-of-concept trial with preliminary data anticipated by year-end 2021

Intrathecal dosing of the high dose first-generation construct resulted in nearly complete normalization of impaired open field and motor function and more than doubled median life expectancy in MSFSD8 knockout mice; data to be presented at upcoming 17th Annual International Congress on Neuronal Ceroid Lipofuscinosis

Taysha also enters into a research collaboration with UT Southwestern to develop next-generation construct for CLN7 disease, which is expected to improve potency, safety profile, packaging efficiency and manufacturability over first-generation construct

Initiation of a planned pivotal CLN7 clinical trial with next-generation construct anticipated in 2022, with reference to human proof-of-concept data generated from first-generation construct

Provides a grant to Batten Hope, the leading CLN7 patient advocacy group, to support patient awareness, disease education and newborn screening initiatives

Estimated prevalence of CLN7 disease is 4,000 patients worldwide

Taysha expected to have five clinical stage programs by year-end 2021

Webcast today at 8:00 AM Eastern Time

DALLAS, October 05, 2021--(BUSINESS WIRE)--Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric, pivotal-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS) in both rare and large patient populations, today announced that it has obtained an exclusive option from UT Southwestern (UTSW) to license worldwide rights to a clinical-stage AAV9 gene therapy replacement program for the treatment of CLN7 disease. The company has also entered into a research collaboration with UTSW to develop a next-generation construct for the treatment of CLN7 disease, which is expected to improve potency, safety profile, packaging efficiency and manufacturability over the first-generation construct. Completion of the next-generation construct design is anticipated by year-end 2021, with commercial-grade GMP material expected in 2022.

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The first-generation construct for the CLN7 program was developed in the laboratory of Steven Gray, Ph.D., Associate Professor at UT Southwestern Medical Center and Chief Scientific Advisor for Taysha, with financial support from Milas Miracle and Batten Hope, the leading CLN7 patient advocacy groups. The CLN7 program is currently in a Phase 1 clinical proof-of-concept trial run by UTSW, and Taysha expects the availability of preliminary human proof-of-concept clinical safety and efficacy data from the first-generation construct by year-end 2021. Taysha intends to initiate a planned pivotal trial using a next-generation construct in 2022, with reference to the human proof-of-concept clinical data being generated from the first-generation construct.

In addition, Taysha has provided a grant to Batten Hope to support patient awareness, disease education and newborn screening initiatives.

CLN7 disease is a rare, fatal and rapidly progressive neurodegenerative disease that is a form of Batten disease. CLN7 is caused by autosomal recessive mutations in the MFSD8 gene that results in lysosomal dysfunction. Disease onset occurs around two to five years of age, with death often ensuing in young adolescence. Patients experience gradual nerve cell loss in certain parts of the brain and typically present with seizures, vision loss, speech impairment and mental and motor regression. Currently, there are no approved therapies to treat CLN7 disease, which impacts an estimated 4,000 patients globally.

Preclinical data in rodents supported advancement of the first-generation construct into a Phase 1 clinical proof-of-concept study in patients with CLN7 disease. In an in vivo efficacy study, intrathecal (IT) administration of the first-generation construct to MFSD8 knockout mice with high or low doses resulted in clear age and dose effects with early intervention and high dose achieving the best therapeutic benefits. IT high dose of the first-generation construct in younger knockout mice resulted in: 1) widespread MFSD8 mRNA expression in all tissues assessed; 2) nearly complete normalization of impaired open field and rotarod performance at 6 and 9 months post injection; 3) more than doubled median life expectancy (16.82 months versus 7.77 months in untreated knockout mice); and 4) maintained healthy body weight for a prolonged period of time. Toxicology studies in wild type rodents demonstrated safety and tolerability of IT administration of the first-generation construct. These preclinical data will be presented by Xin Chen, Ph.D., Assistant Professor, Department of Pediatrics at UT Southwestern, in an oral presentation at the 17th Annual International Congress on Neuronal Ceroid Lipofuscinosis on October 8, 2021.

"The CLN7 program is a strategic addition to our gene therapy pipeline focused on monogenic CNS diseases. Encouraging preclinical data generated in relevant rodent models suggest that the first-generation construct has the potential to reduce overall disease pathology, preserve motor function and ultimately prolong survival," said RA Session II, President, Founder and Chief Executive Officer of Taysha. "The first-generation construct is currently in a Phase 1 clinical proof-of-concept trial with two patients dosed to date, and we look forward to the availability of preliminary data by year-end. With human proof-of-concept clinical data to reference, we expect to advance a next-generation construct into a planned pivotal trial in 2022, which we anticipate should improve potency, safety, packaging efficiency and manufacturability over the first-generation construct. Importantly, we are also pleased to announce our grant to Batten Hope, the leading CLN7 disease nonprofit patient advocacy organization, to support patient awareness, disease education and newborn screening initiatives. We believe a gene therapy approach has the potential to address a significant unmet need in an estimated 4,000 patients globally."

Gina Hann, Batten Hope Founder, President and Treasurer, added, "Our mission is to support families with children suffering from terminal and rapidly progressive neurodegenerative diseases like CLN7. We are honored to receive Tayshas support to raise awareness, increase newborn screening and help patients gain access to potentially transformative treatments that offer hope and therapeutic advancement for conditions with significant unmet needs."

UTSW is currently enrolling patients in an investigator-sponsored Phase 1 open-label, dose escalation clinical proof-of-concept trial at Dallas Childrens Hospital for an intrathecally dosed AAV9-based gene replacement therapy for the treatment of infantile CLN7 disease. The primary endpoint of the trial is safety and tolerability by incidence and severity of treatment related serious adverse events. Secondary efficacy endpoints include the Clinical Global Impression, neuropsychological, ataxia and motor function assessments and quality of life. The design rationale and a discussion of outcome measures for this clinical trial will be presented as a poster at the upcoming 17th Annual International Congress on Neuronal Ceroid Lipofuscinosis. To date, one patient has been dosed at 5x1014 total vg and a second patient was dosed at 1x1015 total vg as measured by the qPCR method. UTSW continues to enroll patients in this Phase 1 study at 1x1015 total vg and expects to dose additional patients in the near term. Preliminary safety and efficacy data are expected by the end of 2021.

With the addition of the CLN7 program, Taysha expects to have five clinical stage programs by year-end. As such, the TSHA-104 program for the treatment of SURF1-associated Leigh syndrome will transition to the companys collaborators at UTSW to complete IND-enabling studies, followed by a planned investigator-initiated clinical trial by the end of 2022. Taysha will continue to support the SURF1 natural history study in partnership with UTSW.

Financial terms of the agreements were not disclosed.

Webcast Information

Taysha management will host a webcast today at 8:00 am ET / 7:00 am CT to discuss todays news. To participate, please access the following link: http://lifesci.rampard.com/WebcastingAppv5/Events/eventsDispatcher.jsp?Y2lk=MTQ1MQ==. The live webcast and replay may also be accessed by visiting Tayshas website at https://ir.tayshagtx.com/news-events/events-presentations. An archived version of the webcast will be available on the website for 60 days.

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a singular focus on developing curative medicines, we aim to rapidly translate our treatments from bench to bedside. We have combined our teams proven experience in gene therapy drug development and commercialization with the world-class UT Southwestern Gene Therapy Program to build an extensive, AAV gene therapy pipeline focused on both rare and large-market indications. Together, we leverage our fully integrated platforman engine for potential new cureswith a goal of dramatically improving patients lives. More information is available at http://www.tayshagtx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipates," "believes," "expects," "intends," "projects," and "future" or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements concerning the potential of our product candidates, as well as the CLN7 program, to positively impact quality of life and alter the course of disease in the patients we seek to treat, our expectations regarding the benefits of a next-generation construct for CLN7, our research, development and regulatory plans for our product candidates, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed, and the potential market opportunity for these product candidates. Forward-looking statements are based on managements current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission ("SEC") filings, including in our Annual Report on Form 10-K for the full-year ended December 31, 2020, and our Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, both of which are available on the SECs website at http://www.sec.gov. Additional information will be made available in other filings that we make from time to time with the SEC. Such risks may be amplified by the impacts of the COVID-19 pandemic. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211005005463/en/

Contacts

Company Contact: Kimberly Lee, D.O.SVP, Corporate Communications and Investor RelationsTaysha Gene Therapiesklee@tayshagtx.com

Media Contact: Carolyn HawleyCanale Communicationscarolyn.hawley@canalecomm.com

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Taysha Announces Exclusive Option from UTSW to License Worldwide Rights to Clinical-Stage AAV9 Gene Therapy Program for CLN7 Disease, a Research...

Recommendation and review posted by Bethany Smith

Dive Brief:

When Amicus acquired a privately held biotech called Celenex in 2018, it appeared to signal a new direction for a company that had already been around for almost two decades. Amicus spent all that time developing chemical drugs known as "pharmacological chaperones," and after a series of ups and downs, had finally brought the first of them, Galafold, to market.

Acquiring Celenex, however, made Amicus a gene therapy developer too. Celenex had several research programs that originated within Nationwide Children's Hospital, one of the nation's top gene therapy hubs. Amicus has since bought several others from the University of Pennsylvania, further establishing gene therapy research as a top priority and quietly giving the New Jersey biotech one of the larger portfolios in the industry.

But Amicus has paid a price, as it still isn't profitable despite having an approved product. The company spent nearly $500 million on expenses last year, largely to fund its pipeline. Its shares also continue to hover around $11 apiece, almost exactly where they were when the biotech began its gene therapy work three years ago.

The value of those assets "has largely gone unrecognized to date," Crowley said on a conference call with analysts. Executives believe housing those assets in a separate company "is the best way to unlock that value for shareholders," he said.

To do this, Amicus has sold its gene therapy business into a special purpose acquisition company, or SPAC, a popular tool of late for biotech investors to take their startups public or acquire stakes in emerging biotechs. The business has been renamed Caritas and will trade on the Nasdaq stock exchange when the deal closes either later this year or early next.

Crowley, who has led Amicus from the start, will join Caritas, which will start with two gene therapies for Batten's disease in clinical testing, several others behind it, more than 115 employees and $400 million in cash. But Amicus will also be able to benefit from Caritas' progress. According to Bradley Campbell, Amicus' chief operating officer and soon-to-be replacement CEO, the company will still hold a 36% stake in its spinout, partial rights to preclinical gene therapies for Fabry and Pompe, and "rights of first negotiation" to others for certain muscular dystrophies.

The companies also believe splitting in two will help each move faster, with Caritas investing solely in gene therapy development and manufacturing and Amicus working to broaden use of Galafold and secure approvals of AT-GAA. Amicus is also getting a $200 million investment from Perceptive and other investors in the deal.

The transaction makes sense given it could "enhance investor interest" in Amicus's gene therapy work, wrote SVB Leerink analyst Joseph Schwartz. Even so, the deal may raise questions about Amicus's long-term growth prospects beyond its two top drugs, wrote Stifel analyst Dae Gon Ha.

"We think investors may question the timing, and its potential significance in the grand scheme of AT-GAA and [Amicus] shares," he wrote.

Amicus shares briefly jumped 10% pre-market before those gains were erased.

See the article here:
Amicus, looking for a boost, sells its gene therapy work to a SPAC - BioPharma Dive

Recommendation and review posted by Bethany Smith

Company to sponsor SCDAA 49th Annual National Convention to be held October 12 to 16, 2021

NEW YORK and BASEL, Switzerland, Oct. 5, 2021 /PRNewswire/ -- Aruvant Sciences, a private company focused on developing gene therapies for rare diseases, today announced that members of the Aruvant leadership team will participate in the annual Cell & Gene Meeting on the Mesa which is taking place in person in Carlsbad, CA and online from October 12 to October 14, 2021. In addition, Aruvant will be a corporate sponsor of the upcoming 49th Annual National Sickle Cell Disease Association of America (SCDAA) Convention to be held October 12 to October 16, 2021, online.

(PRNewsfoto/Aruvant Sciences)

At the Meeting on the Mesa conference, Dr. Palani Palaniappan, Aruvant's chief technology officer, will participate in the panel titled, "What's Next for Advanced Therapies", taking place live Tuesday, October 12 from 7:15 to 8:45 AM PST. In addition, Dr. Will Chou, chief executive officer, will give a company presentation and provide an update on the development of ARU-1801, an investigational lentiviral gene therapy for sickle cell disease (SCD), and ARU-2801, a one-time, adeno-associated virus gene therapy designed to deliver potentially curative efficacy to patients with hypophosphatasia without the limitations of chronic administration. The presentation will include ARU-2801 preclinical data and clinical data from the ongoing Phase 1/2 MOMENTUM study of ARU-1801 in patients with severe SCD.

In addition, Aruvant is a sponsor of the SCDAA annual meeting. SCDAA's Annual National Convention is a four-day conference designed to address the multifactorial aspects of SCD and sickle cell trait. This year's theme is "Unstoppable: Working Together for Sickle Cell". Click here to view the full program. The Aruvant Meeting on the Mesa presentation and panel discussion will be available for registered participants at http://www.meetingonthemesa.com on October 12, 2021.

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About Aruvant SciencesAruvant Sciences, part of the Roivant family of companies, is a clinical-stage biopharmaceutical company focused on developing and commercializing gene therapies for the treatment of rare diseases. The company has a talented team with extensive experience in the development, manufacturing and commercialization of gene therapy products. Aruvant has an active research program with a lead product candidate, ARU-1801, in development for individuals suffering from sickle cell disease (SCD). ARU-1801, an investigational lentiviral gene therapy, is being studied in a Phase 1/2 clinical trial, the MOMENTUM study, as a one-time potentially curative treatment for SCD. Preliminary clinical data demonstrate engraftment of ARU-1801 and amelioration of SCD is possible with one dose of reduced intensity chemotherapy. The company's second product candidate, ARU-2801, is in development to cure hypophosphatasia, a devastating, ultra-orphan disorder that affects multiple organ systems and leads to high mortality when not treated. Data from pre-clinical studies with ARU-2801 shows durable improvement in disease biomarkers and increased survival. For more information on the ongoing ARU-1801 clinical study, please visit http://www.momentumtrials.com and for more on the company, please visit http://www.aruvant.com. Follow Aruvant on Facebook, Twitter @AruvantSciences and on Instagram @Aruvant_Sciences.

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SOURCE Aruvant Sciences

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Aruvant to Participate in 2021 Cell & Gene Meeting on the Mesa to be Held Online and in Person October 12 to 14, 2021 - Yahoo Finance

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