Data protection watchdogs in Canada and the UK have announced a joint investigation into a data breach at genetics testing company 23andMe that affected seven million customers in 2023.

Since 2006, San Francisco-based genetic testing company 23andMe has sold over 12 million DNA testing kits. It analyses customers saliva to provide insights into health and ancestry.

In October 2023, 23andMe reported a security breach in which hackers gained access to the personal information of millions of customers by using old passwords. In some cases, the information accessed included family trees, birth years and geographic locations.

The Information Commissioner's Office (ICO) in the UK and the Office of the Privacy Commissioner of Canada (OPC) will examine the scope of information that was exposed by the breach and potential harms to affected people.

John Edwards, the UK information commissioner, said: People need to trust that any organisation handling their most sensitive personal information has the appropriate security and safeguards in place.

He added: This data breach had an international impact, and we look forward to collaborating with our Canadian counterparts to ensure the personal information of people in the UK is protected.

The strength of 23andMes safeguards to protect the information within its control will also be investigated, as well as whether the company provided adequate notification about the breach to the two regulators and affected people.

Philippe Dufresne, the Canadian privacy commissioner, said: In the wrong hands, an individuals genetic information could be misused for surveillance or discrimination. Ensuring that personal information is adequately protected against attacks by malicious actors is an important focus for privacy authorities in Canada and around the world.

According to the Guardian, a 23andMe spokesperson had previously said that the company did not detect a breach within its systems and instead attributed the incident to compromised recycled login credentials from certain users.

However, 23andMe has said it will cooperate with the investigation and the regulators reasonable requests.

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Genetics testing company 23andMe to be probed over a data breach that affected 7 million users - E&T Magazine

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Around the world, hundreds of people have had their bodies frozen at extremely low temperatures, just after death in the hope that they can be revived in the future.

Some are so confident that theyll wake up in the future that their loved ones have left them voicemail messages.

But the moment when people can be revived by science could come sooner than we expect, according to Dennis Kowalski of Michigans Cryonics Institute.

MORE: Woman in her 30s kidnapped and gang raped in broad daylight at Essex graveyard MORE: Couple held after 13 children found chained to their beds in California home

Kowalski told the Daily Star, If you take something like CPR, that would have seemed unbelievable 100 years ago. Now we take that technology for granted.

Cryonically bringing someone back to life should definitely be doable in 100 years, but it could be as soon as ten.

Companies pump peoples brains full of cryoprotectant fluid before being frozen in the hope the brains will last decades or even hundreds of years.

Many cryonics fans have their heads frozen not their whole bodies imagining that in the future, brain transplants will be possible.

Kowalski says that innovations in technologies such as stem cells may make it possible to revive frozen bodies at some point in the future.

Another tech company, Humai is monitoring developments in robotics, medical treatments and believes people will come back from the dead within 30 years.

The company believes that within three decades, technology will have advanced so that people can freeze their brains then have them transplanted into an artificial, robot-like body after death.

CEO Josh Bocanegra told Popular Science, Well first collect extensive data on our members for years prior to their death via various apps were developing.

After death well freeze the brain using cryonics technology. When the technology is fully developed well implant the brain into an artificial body. The artificial body functions will be controlled with your thoughts by measuring brain waves.

As the brain ages well use nanotechnology to repair and improve cells. Cloning technology is going to help with this too.

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Humans frozen by cryogenics 'could be brought back to life in 10 years' - Yahoo Canada Shine On

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Ive had many conversations over the years about life extension, and the idea often meets resistance. People become upset when they hear of an individual whose life has been cut short by a disease, yet when confronted with the possibility of generally extending all human life, they react negatively. Life is too difficult to contemplate going on indefinitely is a common response. But people generally do not want to end their lives at any point unless they are in enormous painphysically, mentally, or spiritually. And if they were to absorb the ongoing improvements of life in all its dimensions, most such afflictions would be alleviated. That is, extending human life would also mean vastly improving it.

But how will nanotechnology actually make this possible? In my view, the long-term goal is medical nanorobots. These will be made from diamondoid parts with onboard sensors, manipulators, computers, communicators, and possibly power supplies. It is intuitive to imagine nanobots as tiny metal robotic submarines chugging through the bloodstream, but physics at the nanoscale requires a substantially different approach. At this scale, water is a powerful solvent, and oxidant molecules are highly reactive, so strong materials like diamondoid will be needed.

And whereas macro-scale submarines can smoothly propel themselves through liquids, for nanoscale objects, fluid dynamics are dominated by sticky frictional forces. Imagine trying to swim through peanut butter! So nanobots will need to harness different principles of propulsion. Likewise, nanobots probably wont be able to store enough onboard energy or computing power to accomplish all their tasks independently, so they will need to be designed to draw energy from their surroundings and either obey outside control signals or collaborate with one another to do computation.

To maintain our bodies and otherwise counteract health problems, we will all need a huge number of nanobots, each about the size of a cell. The best available estimates say that the human body is made of several tens of trillions of biological cells. If we augment ourselves with just 1 nanobot per 100 cells, this would amount to several hundred billion nanobots. It remains to be seen, though, what ratio is optimal. It might turn out, for example, that advanced nanobots could be effective even at a cell-to-nanobot ratio several orders of magnitude greater.

One of the main effects of aging is degrading organ performance, so a key role of these nanobots will be to repair and augment them. Other than expanding our neocortex, this will mainly involve helping our nonsensory organs to efficiently place substances into the blood supply (or lymph system) or remove them. By monitoring the supply of these vital substances, adjusting their levels as needed, and maintaining organ structures, nanobots can keep a persons body in good health indefinitely. Ultimately, nanobots will be able to replace biological organs altogether, if needed or desired.

But nanobots wont be limited to preserving the bodys normal function. They could also be used to adjust concentrations of various substances in our blood to levels more optimal than what would normally occur in the body. Hormones could be tweaked to give us more energy and focus, or speed up the bodys natural healing and repair. If optimizing hormones could make our sleep more efficient, it would in effect be backdoor life extension. If you just go from needing eight hours of sleep a night to seven hours, that adds as much waking existence to the average life as five more years of lifespan!

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The Secret to Living Past 120 Years Old? Nanobots - WIRED

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Study design

A dual-center, retrospective study of patients undergoing HCT for SAA was conducted at Vanderbilt University Medical Center (VUMC) and the associated Veterans Affairs hospital, Tennessee Valley Healthcare System (TVHS). The VUMC and TVHS Institutional Review Board approved the study. Patients with a SAA diagnosis who underwent first allogeneic HCT using FCR conditioning regimen at VUMC or TVHS between January 2016 and May 2022 were included in the study. Patients were excluded if they were younger than 18 or had not completed all planned treatments at the time of data collection.

All patients received conditioning per established protocol as determined by degree of HLA-matching with their designated donor (Fig.1). Patients received PBSC or BM grafts per treating physicians discretion with allogeneic HCT performed on day 0. In patients with matched related, matched unrelated, or 1-allele mismatched donors, fludarabine (30mg/m2) was given intravenously for four days (7 to 4, i.e., 7 to 4 days before transplantation) in combination with cyclophosphamide (750mg/m2) given intravenously for three days (6 to 4) and anti-thymocyte globulin (rabbit) (3.75mg/kg) for two days (2 and 1). They were also given rituximab (375mg/m2) on days 13, 7, +1, and +8.

Doses and timing of each agent in FCR conditioning regimens for patients undergoing HCT for SAA with matched related, matched unrelated, or 1-allele mismatch donor (a) or haploidentical donor (b). Time in days is represented along the horizontal axis progressing from left to right, with day of transplantation depicted as day 0.

Patients who underwent HCT from a haploidentical donor received fludarabine (30mg/m2) intravenously for five days (6 to 2) and cyclophosphamide (14.5mg/kg) for two days (6 to 5). They also received rituximab (200mg/m2) on day +5. All patients received total body irradiation at a dose of 200cGy on day 0 for those with matched related, unrelated, or 1-allele mismatched donors, or on day 1 for those with haploidentical donors.

Prophylaxis for GVHD in patients with matched related, matched unrelated, or 1-allele mismatch donors consisted of tacrolimus starting on day 3 and methotrexate, 5mg/m2 intravenously, on days +1, +3, and +6 after transplantation. Patients with haploidentical donors received standard post-transplant cyclophosphamide (50mg/kg on days +3 and +4), and tacrolimus and mycophenolate mofetil starting on day +5. Tacrolimus levels were adjusted to a goal range of 515ng/mL per institutional standard, and administered for 180 days, at which point a taper was initiated provided absence of GVHD. Mycophenolate mofetil was administered until day +35 in patients with haploidentical donors.

The primary outcome of interest was GVHD-free/relapse-free survival. A patient was considered to have an event if they experienced moderate or severe GVHD (including both acute GVHD [aGVHD] and cGVHD), relapse, or death. If a patient experienced multiple events, the earliest event date was used as the time to event (e.g., if a patient had a diagnosis of both aGVHD and cGVHD, the earliest date of diagnosis was used). If a patient did not experience an event until the end of follow-up time (i.e., the last date the patient was seen in the clinic or lost to follow-up [unable to contact, transitioned care to another city, etc.]), it was censored. Acute and chronic GVHD were graded according to Glucksburg and 2014 National Institutes of Health consensus criteria, respectively [17, 18]. Secondary outcomes included time to engraftment, incidence of graft failure, incidence of GVHD, rate of viral reactivation, post-HCT disease status, and number of inpatient hospital days.

Descriptive statistics were used to summarize the patient characteristics. Medians and interquartile ranges (IQRs) were used for continuous variables, while frequencies and percentages were used for categorical variables. Differences in patient characteristics were tested for using Wilcoxon rank sum tests for continuous variables and chi-square tests for categorical variables. Probability of GRFS over time was estimated using the Kaplan-Meier estimation method.

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Efficacy and safety of outpatient fludarabine, cyclophosphamide, and rituximab based allogeneic hematopoietic cell ... - Nature.com

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Salute to saving a life: Local Air Force man answers the call for stem cell donation - Citrus County Chronicle

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Key Takeaways

CAR-T cell therapy doesnt increase a persons risk of secondary cancers, researchers reportThe risk of a secondary cancer is slightly more than 6%, about the same as stem cell transplantation to treat blood cancersOther factors appear to be involved in secondary cancers

THURSDAY, June 13, 2024 (HealthDay News) CAR-T cell therapy to treat blood cancers is safer than previously thought, with little risk that the immunotherapy will create secondary cancers, a new study finds.

The U.S. Food and Drug Administration issued a warning in November 2023 about a risk of secondary cancers that might be associated with CAR-T cell therapy.

But a study of more than 700 patients treated at Stanford University found that the risk was just over 6% in the three years after a cancer patient received CAR-T cell immunotherapy, researchers reported June 13 in the New England Journal of Medicine.

That risk is roughly similar to that of patients who receive stem cell transplants rather than CAR-T cell therapy to treat their blood cancers, researchers said.

These are lifesaving therapies that come with a very low risk of secondary cancers. The challenge lies in how to predict which patients are at higher risk, and why, said researcher Dr. Ash Alizadeh, a professor of medicine at Stanford.

In CAR-T cell therapy, immune cells called T-cells are harvested from a patient and genetically engineered to more efficiently seek out and kill cancer cells.

This therapy typically is used to treat blood cancers like leukemia, lymphoma and multiple myeloma, according to the American Cancer Society.

But one concern is that if the genetic engineering is imprecise, the T-cells meant to attack a persons cancer might instead become cancerous themselves.

To see whether this risk is real, the research team analyzed data drawn from Stanford Medicines large bank of tissue and blood samples from people receiving CAR-T cell therapy.

They found no evidence that the T-cells responsible for some patients secondary cancers were the T-cells that had been engineered for CAR-T cell therapy. The T-cells were distinct on both genetic and molecular levels.

But in one patient who rapidly developed and died from a T-cell lymphoma, researchers found a clue that could explain why secondary cancers sometimes happen.

Both sets of T-cells in that patient the CAR-T cells and the T-cells responsible for the secondary cancer had been infected with a virus known to play a role in cancer development. The patient also had a history of autoimmune disease prior to a cancer diagnosis.

We compared protein levels, RNA sequences and DNA from single cells across multiple tissues and time points to determine that the therapy didnt introduce the lymphoma into this patient; instead it was already brewing in their body at very low levels, Alizadeh said in a Stanford news release.

This suggests that secondary cancers might be prompted by chemotherapy done prior to CAR-T cell therapy, which suppresses a persons immune response to such viruses, researchers said. They also might be due to some other side effect from the treatment, rather than genetic engineering gone wrong.

These results may help researchers focus on the immune suppression that can precede and often follows CAR-T cell therapy, said researcher Dr. David Miklos, chief of bone marrow transplantation and cellular therapy at Stanford Medicine.

More information

The American Cancer Society has more about CAR-T cell therapy.

SOURCE: Stanford University, news release, June 12, 2024

What This Means For You

People with blood cancers can receive CAR-T cell therapy with little fear of increased risk for secondary cancers, researchers say.

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Secondary Tumors After CAR-T Cancer Therapies Are Rare: Study | Fox 11 Tri Cities Fox 41 Yakima - FOX 11 and FOX 41

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DADDY, can we play football?

Those are the most beautiful words in the world to Mo Hussain, 38, from Blackburn, because they mean his five-year-old son Eesa is having a good day.

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And to ensure more good days lie ahead, this devoted father is a man on a mission, seeking the stem cell match that will save his little boys life.

On New Years Day, Eesa felt sick and looked really pale, Mo says. Concerned, we took him to A&E.

Its every parents worst nightmare. A few hours later their son was being transferred by ambulance to Royal Manchester Childrens Hospital.

Normal levels of haemoglobin a protein which transports oxygen around the body are 120-150g/l. Eesas was 42g/l due to dangerously low red blood cell levels.

I want to go home and play with my dinosaurs, Eesa cried. Mos heart broke.

Mo cuddled Eesa as he had a general anaesthetic for a bone marrow biopsy.

That night, the whole family Mo, his wife and two-year-old son Ali crammed into Eesas cubicle on ward 86 to sleep. We needed to be together, Mo says.

The biopsy showed Eesa had a rare, life-threatening condition called aplastic anaemia, meaning his bone marrow and stem cells dont produce enough red and white blood cells and platelets.

The best cure is a bone marrow transplant from a matching donor.

While preparations were made to test the familys suitability, Eesa had a Hickman line fitted in his chest so doctors could administer medicines and take blood.

To make it less frightening, I bought some plastic tubing and stuck it to my chest too, says Mo.

Back home after a week in hospital, the family were on lockdown Eesa off school and Mo and his wife on leave from work.

We cant risk Eesa catching something his bodys weak immune system cant fight, Mo says.

Devastatingly, no one in Eesas family is a donor match for him.

But there is hope. Fifty years ago, Shirley Nolan was so determined to save her son Anthonys life that she set up the worlds first stem cell register.

Since 1974, the charity Anthony Nolan has helped bring about more than 26,500 transplants for people around the world.

If youre from a minority ethnic background, youre more likely to have a rare or completely unique tissue type.

Thats why theres a pressing need to recruit more people from diverse backgrounds to the register to help patients like Eesa find the lifesaving matches they need.

I had to educate our community, Mo says. The team at Anthony Nolan sent me swabs for people to wipe inside their mouths and envelopes to post them back.

And, in February, we set up our first registration stall at a football tournament.

Since then, Mo and his family and friends have visited mosques, universities and football stadiums including the Etihad, Turf Moor and Ewood Park 40 locations in all, adding 1,200 potential new donors to the register.

Sadly, Eesa is still waiting for his match and remains dependant on blood transfusions every three weeks.

I find patience in the words of the Quran saving one life is like saving the whole of humanity, says Mo.

Anthony Nolan shares its register across the world so the people we sign up could save lives in Bangladesh, Pakistan anywhere.

For now, Eesa has good days watching Arsenal and racing his police cars and bad. In April, he was hospitalised because his Hickman line became infected.

Hes the bravest five-year-old in Britain, Mo says. But we just want a normal childhood for him.

The greatest Fathers Day gift I could receive is a match for Eesa. So Im appealing to other dads log on to anthonynolan.org today.

You could save someone like my sons life.

Follow the My Name is Eesa campaign on Instagram at @mynameiseesa

Joining the stem cell register is easy. You must be aged between 16 and 30, as research shows younger donors offer better survival rates for patients.

Fill in a form at anthonynolan.org to receive a swab pack then take a sample and send it back.

Ken (above), 26, from Tower Hamlets, signed up to the register eight years ago at an Anthony Nolan stand handing out Krispy Kreme doughnuts.

And three years later he discovered he was a match for someone.

I was given G-CSF injections at home for four days, he says. G-CSF injections boost white cells and release stem cells into the bloodstream ready to collect.

They gave me minor headaches and muscle pain nothing more. On the fifth day I was in hospital, donating my stem cells and afterwards I was fine.

I hope that more people will join the stem cell register and help Anthony Nolan save the lives of people with blood cancer and blood disorders.

If a family member or friend was diagnosed with blood cancer, it would make such a difference to know that they have a match and a second chance at life.

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Are you under 30? Join the stem cell register and be part of a one million strong team of lifesavers. Sign up at anthonynolan.org

If youre over 30 you can still save lives. It costs Anthony Nolan 40 to recruit each lifesaver to the register, so please support with a gift now!

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Dad urges recruits to sign up in bid to save young son with rare blood condition... - The Irish Sun

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Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced longer-term data for CASGEVY (exagamglogene autotemcel [exa-cel]) from global clinical trials in people with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). The results, presented at the annual European Hematology Association (EHA) Congress, confirm the transformative, consistent and durable clinical benefits of CASGEVY over time. CASGEVY is the first and only approved CRISPR-based gene-editing therapy.

The data being presented are from more than 100 patients (46 SCD; 56 TDT) treated with exa-cel in clinical trials, with the longest follow-up now extending more than 5 years. The efficacy results are consistent with the previously reported primary and key secondary endpoints analyses from these exa-cel studies and continue to demonstrate transformative clinical benefit with durable and stable levels of fetal hemoglobin (HbF) and allelic editing.

The transformative benefit seen in patients with sickle cell disease in the trial is impressive given the significant and cumulative burden of disease faced by people living with this blood disorder, said Haydar Frangoul, M.D., M.S., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcares TriStar Centennial Childrens Hospital. I am eager to offer this therapy and the opportunity of a potential functional cure to my eligible patients.

The comprehensive data set presented today for adult and adolescent TDT patients adds to the growing body of evidence for CASGEVY, and it is important to now ensure the availability of this innovative treatment to patients in the real world as soon as possible, said Franco Locatelli, M.D., Ph.D., Professor of Pediatrics at the Catholic University of the Sacred Heart of Rome, Director of the Department of Pediatric Hematology and Oncology at Bambino Ges Childrens Hospital. With the longest follow up now more than five years, alongside stable editing and sustained fetal hemoglobin levels, I have conviction in the durable benefit to the patients treated with CASGEVY.

New data presented from CASGEVY pivotal trials

In both SCD and TDT patients, edited levels of BCL11A alleles were stable over time in bone marrow and peripheral blood indicating successful editing in the long-term hematopoietic stem cells. All patients engrafted neutrophils and platelets after exa-cel infusion. The safety profile of exa-cel was generally consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.

These longer-term data for CASGEVY from the CLIMB clinical trials will be shared as outlined below:

Vertex will also share five health economics abstracts at the EHA Congress.

About Sickle Cell Disease (SCD)

SCD is a debilitating, progressive, life shortening genetic disease. SCD patients report health-related quality of life scores well below the general population and significant health care resource utilization. SCD affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or sickled red blood cells. The clinical hallmark of SCD is vaso-occlusive crises (VOCs), which are caused by blockages of blood vessels by sickled red blood cells and result in severe and debilitating pain that can happen anywhere in the body at any time. SCD requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In Europe, the mean age of death for patients living with SCD is around 40 years. Stem cell transplant from a matched donor is a potentially curative option but is only available to a small fraction of people living with SCD because of the lack of available donors.

About Transfusion-Dependent Beta Thalassemia (TDT)

TDT is a serious, life-threatening genetic disease. TDT patients report health-related quality of life scores below the general population and significant health care resource utilization. TDT requires frequent blood transfusions and iron chelation therapy throughout a persons life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In Europe, the mean age of death for patients living with TDT is 50-55 years. Stem cell transplant from a matched donor is a potentially curative option but is only available to a small fraction of people living with TDT because of the lack of available donors.

About CASGEVY (exagamglogene autotemcel [exa-cel])

CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patients own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth.

CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT.

CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.

About the CLIMB Studies

The ongoing Phase 1/2/3 open-label trials, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after CASGEVY infusion. Each patient will be asked to participate in the ongoing long-term, open-label trial, CLIMB-131. CLIMB-131 is designed to evaluate the safety and efficacy of CASGEVY in patients who received CASGEVY in other CLIMB studies. The trial is designed to follow patients for up to 15 years after CASGEVY infusion.

U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY (exagamglogene autotemcel)

WHAT IS CASGEVY?

CASGEVY is a one-time therapy used to treat people aged 12 years and older with:

CASGEVY is made specifically for each patient, using the patients own edited blood stem cells, and increases the production of a special type of hemoglobin called hemoglobin F (fetal hemoglobin or HbF). Having more HbF increases overall hemoglobin levels and has been shown to improve the production and function of red blood cells. This can eliminate VOCs in people with sickle cell disease and eliminate the need for regular blood transfusions in people with beta thalassemia.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about CASGEVY?

After treatment with CASGEVY, you will have fewer blood cells for a while until CASGEVY takes hold (engrafts) into your bone marrow. This includes low levels of platelets (cells that usually help the blood to clot) and white blood cells (cells that usually fight infections). Your doctor will monitor this and give you treatment as required. The doctor will tell you when blood cell levels return to safe levels.

You may experience side effects associated with other medicines administered as part of the treatment regimen for CASGEVY. Talk to your physician regarding those possible side effects. Your healthcare provider may give you other medicines to treat your side effects.

How will I receive CASGEVY?

Your healthcare provider will give you other medicines, including a conditioning medicine, as part of your treatment with CASGEVY. Its important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

After receiving the conditioning medicine, it may not be possible for you to become pregnant or father a child. You should discuss options for fertility preservation with your healthcare provider before treatment.

STEP 1: Before CASGEVY treatment, a doctor will give you mobilization medicine(s). This medicine moves blood stem cells from your bone marrow into the blood stream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.

During this step rescue cells are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated just in case there is a problem in the treatment process. If CASGEVY cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in the body, these rescue cells will be given back to you. If you are given rescue cells, you will not have any treatment benefit from CASGEVY.

STEP 2: After they are collected, your blood stem cells will be sent to the manufacturing site where they are used to make CASGEVY. It may take up to 6 months from the time your cells are collected to manufacture and test CASGEVY before it is sent back to your healthcare provider.

STEP 3: Shortly before your stem cell transplant, your healthcare provider will give you a conditioning medicine for a few days in hospital. This will prepare you for treatment by clearing cells from the bone marrow, so they can be replaced with the modified cells in CASGEVY. After you are given this medicine, your blood cell levels will fall to very low levels. You will stay in the hospital for this step and remain in the hospital until after the infusion with CASGEVY.

STEP 4: One or more vials of CASGEVY will be given into a vein (intravenous infusion) over a short period of time.

After the CASGEVY infusion, you will stay in hospital so that your healthcare provider can closely monitor your recovery. This can take 4-6 weeks, but times can vary. Your healthcare provider will decide when you can go home.

What should I avoid after receiving CASGEVY?

What are the possible or reasonably likely side effects of CASGEVY?

The most common side effects of CASGEVY include:

Your healthcare provider will test your blood to check for low levels of blood cells (including platelets and white blood cells). Tell your healthcare provider right away if you get any of the following symptoms:

These are not all the possible side effects of CASGEVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of CASGEVY

Talk to your healthcare provider about any health concerns.

Please see full Prescribing Information including Patient Information for CASGEVY.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency.

Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortunes 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on LinkedIn , YouTube and Twitter/X .

(VRTX-GEN)

Vertex Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the statements by Haydar Frangoul, M.D., M.S., and Franco Locatelli, M.D., Ph.D., in this press release, and statements regarding our expectations for and the anticipated benefits of CASGEVY, our plans to share longer-term data for CASGEVY from the CLIMB clinical trials and to share health economics abstracts at the EHA Congress, and our plans for and design of the CLIMB studies. While we believe the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy, and other reasons, and other risks listed under the heading Risk Factors in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at http://www.sec.gov and available through the company's website at http://www.vrtx.com . You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240613723433/en/

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Media: mediainfo@vrtx.com or International: +44 20 3204 5275 or U.S.: 617-341-6992 or Heather Nichols: +1 617-839-3607

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Vertex Presents Positive Long-Term Data On CASGEVY (exagamglogene autotemcel) at the 2024 Annual European ... - Agenzia ANSA

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There's an assumption that if you're a woman in a heterosexual relationship or marriage going through menopause, you'll have a partner who can step in. But that isn't always a guarantee.

Menopause can put "a huge strain" on relationships, Dr. Deirdre Forde - founder of Cile Medical in Athlone, the first dedicated Menopause Clinic in the Midlands - says, heterosexual or not.

"There's a lot of men who don't know about menopause, don't want to know about menopause and their woman, and their relationship becomes strained because she's turning into a crazy person and he doesn't know who she is anymore.

"And all of a sudden then they start to drift. So when they start to drift then, there's nothing to talk about anymore. Sure, a lot of them end up getting divorced."

"I was one of the one such person", Forde says, adding that she got divorced at 44, six years after starting menopause.

When she started menopause in her late 30s, Forde became gripped by what she calls an "irrational anxiety".

"I describe it like a washing machine, churning in your stomach, that just won't stop", says Forde. "I just wanted to detach my head for my body and make it stop."

Now, imagine you're a menopausal woman or a trans man in a relationship with another menopausal person. Who steps in to pick up the slack then?

Forde has opened up her Athlone practice to LGBT people going through menopause by organising free information events to offer support and advice, on 13 and 15 June.

"We need to talk about menopause as people who are going through menopause, as opposed to women going through menopause", she says. "I want to get rid of that stigma. There's nobody judging you. You are a person like everybody else, and you are going to go through this transition."

How we talk about the menopause has shifted radically in recent years, both globally and at home. A notable watershed moment in this shift was when scores of Irish women contacted Liveline with their often anguished accounts of menopause for five days straight, releasing years of suppressed pain.

Compounding this has been a glut of new research into the once mysterious part of a woman's life. This also backed up what many women had been saying in no uncertain terms: 55% of Irish women described menopause and perimenopause as a negative experience, compared to 22% calling it positive.

On top of that, an overwhelming majority of women (93%) agreed on menopause having a significant impact on a woman's life.

Menopause is defined as having had no period for 12 months, or if a woman has no ovaries due to surgery. It's caused by a drop in the production of key hormones estrogen, progesterone, and testosterone. It can span anywhere from four to 11 years and can bring on symptoms ranging from night sweats, mood swings and brain fog, to disrupted sleep, a burning sensation in the mouth and vaginal dryness.

Depending on the person, the stakes are undeniably high when it comes to untreated menopause, Forde says. Of course, there will always be some who practically sail through the experience, barely noticing a change. But the majority will undergo often seismic shifts in their physical and mental health. Research shows that fluctuating hormones can even have a lasting effect on the brain's structure.

"You're going to get women who just don't feel themselves anymore, who don't know who they are anymore. They feel that they can't work. They feel that they can't contribute to society anymore. Their brain is foggy and all of that. But they just feel worthless."

In some cases, those affected can become suicidal*, she says. People living with preexisting mental health conditions are particularly at risk.

"You've really got to watch a woman who, all of a sudden, is changing. Her mood is changing. Her mood swings are horrendous and her rage is terrible. She's not sleeping and she has uncontrollable anxiety. She's a menopausal woman and she needs help."

Finding the right support during menopause can still be challenging, particularly for LGBT people, she adds.

Although she herself hasn't treated any trans men presenting with menopause, she stresses that, "it is going to happen". "I am now 64, so I won't be doing this forever. But the new doctors coming on board who are hopefully going to be treating an awful lot of people with menopause, they're going to see it.

"I suppose trans people need to be aware. Trans men who are born with a uterus or who are born female, they need to be aware that they're going to face this in the future."

Forde's aim isn't to scaremonger, but to illuminate the reality of what many people experience. The hope is that in doing so, generations of people can prepare for the shift. There are already 600,000 menopausal women in Ireland, and by 2030 it is estimated that there will be 1.1 billion menopausal women on the planet.

Increased research and a greater understanding of hormone replacement therapy (HRT) and other treatments has made managing menopause considerably easier for many people.

Although a 1990s study - the Women's Health Initiative, which set out to examine the link between HRT and cardiovascular disease and studied the health of 160,000 postmenopausal women - skewed public perception against HRT, suggesting that it caused breast cancer, greater research has now shown that such risks are low for healthy women under the age of 60 and HRT is still a profoundly helpful treatment option for many women.

With the right treatment, Forde says, "You've got the benefit in that you've got your quality of life back. You're able to function as a person in this society. You're able to work, you're able to be happy."

To register for the free sessions on Saturday 15 June at 11am and 3pm email info@ceilemedical.ie with your name and age.

*If you are affected by any of the issues raised in this article, you can contact The Samaritans (phone: 116123), or Pieta House (1800 247 247).

More:
Meet the doctor giving free menopause support to LGBT people - RTE.ie

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When researcher Arkasubhra Ghosh finally met Uditi Saraf, he hoped that there was still a chance to save her.

Ghosh and his collaborators were racing to design a one-off treatment that would edit the DNA in the 20-year-old womans brain cells and get them to stop producing toxic proteins. It was an approach that had never been tried before, with a long list of reasons for why it might not work.

CRISPR cures and cancer vaccines: researchers can help to shepherd them to market

But the team was making swift progress. The researchers were maybe six months away from being ready to give Uditi the therapy, Ghosh told her parents over breakfast at their home outside New Delhi last June. Even so, Uditis mother was not satisfied. Work faster, she urged him.

Then, Uditi was carried to the breakfast table, and Ghosh understood her urgency. Once a gregarious and energetic child and teenager, with a quick laugh and a mischievous streak, Uditi was now unable to walk or feed herself. She had become nearly blind and deaf. Her family tried to talk to her: These are the people who are making a therapy for you, they said loudly.

Shaken, Ghosh returned to his gene-therapy laboratory at Narayana Nethralaya Eye Hospital in Bengaluru, India, and got to work. If you need to put up tents in the lab, then we can do so, he told his students. Im not going to sleep.

Four months later, Uditi was gone.

The first therapy using CRISPR genome editing was approved in late 2023 to treat blood disorders that affect thousands of people worldwide. But the approach is also a source of hope to many people who have extremely rare genetic conditions, like the one Uditi had. Genome editing could one day become a radical way to address the diseases that are overlooked by pharmaceutical companies. Patients are waiting, families are waiting, says Jennifer Doudna, a molecular biologist at the University of California, Berkeley. So we need to get on with it.

How personalized cancer vaccines could keep tumours from coming back

Researchers are still laying the groundwork for this future. They are working out how best to design and manufacture the treatments, and how to deliver them to precise locations in the body. The cost is also a problem: the price of genome-editing therapy threatens to put it out of reach for many. Ghosh wants to bring those barriers down, and hes convinced that India will eventually be the country to do it.

But Uditis family could not wait the pace of scientific research was too slow. They needed a sprint, and a team of researchers willing to take on not only the scientific challenge, but also the emotional heft and high risk of failure involved in attempting something that had never been done. What we were trying to do was really almost in the realms of science fiction, Ghosh says.

And he remains convinced that, despite Uditis tragic death, the lessons learnt will help others on a similar path. It truly is a story of hope.

As a young girl, Uditi was always in a hurry. Seizing any excuse to celebrate whether it was a birthday or a festival she would buzz around the house getting ready hours ahead of everyone else, peppering her mother with urgent requests. She greeted family and friends with cuddles and kisses and brightened parties with her laughter and dancing.

For the first nine years, there was no hint of trouble. And when it began, it was just a flicker a few seconds here and there, when Uditi would zone out.

Shed switch back on again as if nothing had happened, and her mother, Sonam, wasnt sure if she should worry. But then Sonam saw nine-year-old Uditi drop a camera on the floor and become confused as to why it was no longer in her hand. A mothers hunch hardened: something was wrong.

Uditi Saraf with her mother, Sonam Saraf.Credit: Rajeev and Sonam Saraf

The physicians diagnosed her with epilepsy. When Uditis seizures became more pronounced and she began to struggle at school, Sonam and Rajeev, Uditis father, decided it must be something more. In 2017, they had part of Uditis genome sequenced.

It was a deviation from the standard treatment path, but the Sarafs were technologically savvy and financially well off. In India, as in many places in the world, genome sequencing was still uncommon, its roll-out slowed both by the costs and by the dearth of genetic information from people of Indian descent in genetic databases. Without such data, it can be difficult to interpret sequencing results.

Uditis results, however, were unambiguous: a single-base change in the gene that codes for a protein called neuroserpin caused tangled polymers to form in her brain cells, interfering with their function. Uditis neurons were dying.

This condition is called FENIB (familial encephalopathy with neuroserpin inclusion bodies), and the symptoms which can be similar to dementia usually manifest late in life. Elena Miranda, a cell biologist at the Sapienza University of Rome, runs the worlds only lab that focuses on the disease. She says that its possible that many cases of FENIB go unreported because physicians do not often sequence the genomes of older adults with dementia.

How CRISPR gene editing could help treat Alzheimers

But the most severe forms of FENIB strike early and are exceedingly rare. Miranda has known of only three other people with the same mutation that Uditi had. This form of the disease is very aggressive, she says.

Uditi and her parents embarked on a lonely journey familiar to many people with rare diseases. They had never heard of FENIB, and neither had Uditis physicians. Sonam did some research but couldnt bring herself to fully absorb what she found. We thought its not possible, she says. It cannot happen with our daughter.

The Sarafs studied what they could find online and tried the interventions available to them: Indian ayurvedic treatments, a ketogenic diet, special schools, seeing a slew of physicians and trying out various medicines. We shopped for doctors. We shopped for gods, says Sonam, but Uditis condition slowly worsened.

The three moved to upstate New York in 2018 to send Uditi to a school for people with disabilities. Her seizures intensified, and frequent muscle spasms made it hard for her to walk or drink from a glass. Her bright personality was dimming. The Sarafs discussed experimental treatments with Uditis new physician, epilepsy specialist Orrin Devinsky at NYU Langone Health in New York City. Devinsky mentioned a couple of options, one of which was CRISPR genome editing. Rajeev seized on the idea.

Uditis disease was caused by a mutation that converts a single DNA base from a G to an A. A variation on CRISPR genome editing, called base editing, could theoretically correct exactly this kind of mutation (see Precision gene repair).

Devinsky also emphasized the difficulties. At that time, base editing which was first reported in 2016 had never been tested in a clinical trial. The technique requires shuttling a relatively large protein and a snippet of RNA into affected cells. Researchers were struggling with how to perfect this delivery for many organs the brain being one of the most daunting.

Even if each of these hurdles were surmounted, at best, base editing might stop the production of neuroserpin clumps in some of Uditis neurons. The treatment was unlikely to reach all affected cells, and it was unlikely to clear the clumps that were already present or to regenerate neurons that had been lost.

But Rajeev and Sonam saw an opportunity for hope: perhaps such a therapy could slow down the progression of Uditis disease, buying time for scientists to develop another treatment that could repair the damage that had been done. The Sarafs were on board.

Devinsky assembled a team at NYU Langone Health with expertise in genome editing and neuroscience to conduct preliminary studies of the approach. The researchers pulled together what funding they could from other grants, and the Sarafs funded the rest. We will sell our house if we have to, Sonam said.

The pressure in the lab was intense, says team member Jayeeta Basu, a neuroscientist at NYU Langone Health. The team genetically engineered Uditis FENIB mutation into cells grown in the lab. When the cells initially didnt seem to behave as expected, Basu asked her graduate student to repeat the experiment five times. I was always pushing, she says. We had to be fast, but we also had to be diligent. There was no short cut.

Rajeev Saraf with his daughter Uditi.Credit: Rajeev and Sonam Saraf

In December 2019, the Sarafs moved back to India. Maintaining a home in the United States was expensive, and Uditi missed her extended family. Then the COVID-19 pandemic struck, and in January 2021, Uditi was hospitalized with severe COVID-19. She spent 20 days in the hospital and her health was never the same, says Sonam. Communication became increasingly difficult for Uditi and she began to pace the house incessantly, rarely even going to sleep.

The Sarafs decided to speed up the base-editing project by funding a second team in India.

Meanwhile, Devinsky had petitioned a US foundation to devise a different experimental treatment called antisense therapy for Uditi. The family flew from India to the United States twice for injections into her spine. The trips became traumatic as her ability to understand the world around her declined.

CRISPR 2.0: a new wave of gene editors heads for clinical trials

The treatments didnt work. And the experience taught Rajeev and Sonam how long it could take to get approval to try an experimental therapy in the United States. They decided Uditis base-editing therapy should also be manufactured and administered in India.

About an hour and a half away from their home, Debojyoti Chakraborty, a geneticist at the Council of Scientific and Industrial Researchs Institute of Genomics and Integrative Biology in New Delhi, had been making headlines for his efforts to devise a CRISPR-based treatment for a genetic blood disorder called sickle-cell disease.

Researchers in the United States were also developing genome-editing therapies for sickle-cell disease, but those therapies were expected to be expensive and potentially out of reach for much of the world. (The UK Medicines and Healthcare Products Regulatory Agency approved the first one, Casgevy, made by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland, which costs US$2.2 million per patient.)

Most of the people with sickle-cell disease in India a country with one of the highest rates of the condition live in impoverished communities. Chakraborty and his colleagues hoped to develop a therapy that could be produced and administered at a fraction of the price that is charged in the United States, if not less.

Debojyoti Chakraborty is trying to develop affordable CRISPR-based treatments in India.Credit: RNA Biology Lab

Rajeev and Sonam went to the institute to talk to Chakraborty and the institutes director, chemist Souvik Maiti, who had been collaborating with Chakraborty on the CRISPR technology behind the sickle-cell project.

Move over, CRISPR: RNA-editing therapies pick up steam

Although the institute gets many requests for help from people with rare diseases and their caregivers, the Sarafs were unusual in that they would be able to help fund the work, says Maiti. Uditi was the only person in India known to have her neuroserpin mutation, and no government agency, company or philanthropy was likely to pay for the development of a treatment. Its very difficult, Maiti says. Even if our heart is telling us we should work on it, until there is funding, we cannot do it.

Even with funding, Maiti and Chakraborty took some time to discuss the project with Ghosh, who was building a facility in Bengaluru to produce viruses called adeno-associated viruses (AAVs), which are often used in gene therapies. Ghosh aimed for his facility to be one of the first in India to produce AAVs to the standards required for use in people.

There were a lot of unknowns in the base-editing project. And in addition to the work on stem cells in the lab, the team would need to do further experiments to determine which base-editing systems would work best, where and how to deliver its components into the body, and whether the process generated any unwanted changes to the DNA sequence. They would need to do experiments in mice to test the safety and efficacy of the treatment. They also needed to get Ghoshs facility approved by Indias regulators for producing the base-editing components.

Uditis illness had probably already progressed beyond the point at which the therapy could offer a notable benefit, but the family wanted them to try, reasoning that the work that they did on this project could help future endeavours to develop genome-editing therapies for genetic conditions.

It was not the first time Ghosh was swayed by a personal appeal: a few years before he met Uditi, Ghosh came to work and found two women waiting outside of his office. They would not leave, the women said, until he committed to finding a treatment for their young sons illness, a genetic condition called Duchenne muscular dystrophy, which can be fatal. The women pledged to help raise funds, and Ghosh found himself unable to say no. He has worked on the project and grown close to the families since then.

UK first to approve CRISPR treatment for diseases: what you need to know

Lab protocols for making medicines are notoriously strict, with each step carefully controlled to minimize the chance of contamination. When setting up his facility for manufacturing gene therapies, Ghosh scrutinized each step, looking for ways to cut costs without sacrificing safety, arguing his case to Indias regulators. He estimates that gene therapies for eye diseases that are developed in his lab will one day be available for one-hundredth of what they cost in the United States. We will certainly short circuit this entire field, Ghosh says.

India has earned a reputation for making complex drugs on a budget. During the COVID-19 pandemic, Indian manufacturers cranked out millions of doses of vaccines. Now, the country is manufacturing a malaria vaccine at a fraction of the cost of that in Europe, and it is developing sophisticated cell and gene therapies used in cancer treatments for much less than the price of those in the United States.

Chakraborty took the lead on Uditis project. He is a go-getter kind of person, says Riya Rauthan, who was then a PhD student in Chakrabortys lab. He is not bothered by who he needs to ask to get something done, he just does it.

To minimize interruptions, the team mapped out all of the experiments and the components they would need from start to finish. In India, many lab reagents have to be imported, and supply interruptions can delay projects by weeks or months. Everything had to be planned and ordered ahead of time, and Maiti worked to keep the supplies coming, seeking out vendors and negotiating prices. Time was more valuable than anything else, he says.

One of the most important reagents had to come from abroad: antibodies that could recognize the neuroserpin protein and its tangles. Few researchers use such antibodies, and the supply was uncertain. The team decided that the quickest way to get reliable antibodies was to ask Miranda in Rome to share the ones she had developed. She gladly did. This was a desperate approach, she says. But for me the priority was to try to help as much as I could.

Rauthan generated stem cells from samples of Uditis blood. Then, she and her colleagues coaxed those cells to become neurons, and used base editing on them in the lab.

Arkasubhra Ghosh is building an Indian facility to make viral vectors for gene therapy.Credit: Arkasubhra Ghosh

Ghosh worked on preparing the AAV that would be used to transport the CRISPR components into Uditis neurons. The team needed to determine which strain of AAV would work best some strains could trigger inflammation in the brain. Ghoshs lab tested several types of AAV in mice, to find out which one caused the least amount of inflammation and how best to administer it. The team eventually settled on one type called AAV9 and determined that it should be injected directly into Uditis brain.

Still, that was not the end of their challenges. AAV genomes can carry only an extra 4,700 DNA bases, but the gene that codes for the enzyme needed in base editing is longer than that. Ghosh and his students worked to divide up their genomic cargo so that it could fit in two separate viruses, and added sequences that would allow the two pieces to be spliced together again when they are expressed inside a cell. The team would inject both viruses at the same time.

The approach has been shown to work in mice but had not yet been tested in humans (J. M. Levy et al. Nature Biomed. Eng. 4, 97110; 2020).

By June 2023, the team seemed to be barrelling towards the finish line. Many of the researchers were working 10-to-12-hour days, and it was nearly time to test their therapy in mice. Ghosh was also scheduling a regulatory inspection to ensure that he would have the approvals he needed by the time the animal results were in. A surgeon had agreed to perform Uditis injection.

If all went well, they might be ready to treat Uditi in as little as six months, Chakraborty predicted.

In early October, a few months after Chakraborty and Ghosh had breakfast with Uditi and her parents, the team received a series of messages from Rajeev on their WhatsApp group. Uditi had become ill with pneumonia and had been taken to the hospital. Then she was in a coma and had been sent home there was nothing else the physicians could do for her.

Soon afterwards came the message they had all feared: Uditi was gone.

Ghosh thought immediately of the two little boys with Duchenne muscular dystrophy: What if Im too late for them, too?

Others in the lab also took the news hard. For clinicians, perhaps they become hardened, says Chakraborty. We dont have that experience. We were feeling agony.

Ten days after learning that Uditi died, Chakraborty presented the labs efforts at a local conference and finished his talk with a picture of Uditi, smiling. In the audience, Riya Patra, a graduate student in Ghoshs lab, began to cry. It was the first time shed let herself see a picture of the young woman shed tried so hard to save. Before, I had thought that if I saw her, maybe I would cry, she says. And I wouldnt be able to work anymore.

Is CRISPR safe? Genome editing gets its first FDA scrutiny

An estimated 100 million people in India have a rare disease. For decades, people affected by such conditions have cycled through hope and disappointment as researchers have inched closer to developing therapies that can help them at a genetic level. After a series of sporadic starts and failures, gene therapy has finally begun to find its footing. This has set the stage for CRISPR-based genome editing to rocket to the clinic.

When nine-year-old Uditi first dropped her camera, CRISPR was just an oddity a strange assembly of sequences found in microbial genomes, only studied by a few die-hard microbiologists. Four years before she was diagnosed with FENIB, researchers showed for the first time that a CRISPR-based system could cut DNA in human cells grown in the lab. And the first CRISPR-based genome-editing therapy was approved in the United Kingdom to treat sickle-cell disease the month after Uditi died.

In theory, many people with a genetic condition, no matter how rare, could benefit from these technologies. But the reality is harsher. It will take years to establish the techniques needed to create rapid, on-demand, bespoke CRISPR therapies. Most people with these conditions dont have that kind of time.

But researchers are working to streamline the process. Doudnas institute, for example, is working to standardize some aspects of genome-editing therapies, in part to make it cheaper and easier to develop such treatments for people with rare conditions. And the US National Institutes of Health has been trying to develop similar pipelines for gene therapies an effort that could help to inform genome-editing efforts. Its been really hard, says Doudna. But what were doing is going to have long-term impact.

In India, the work has continued. Rajeev has urged Chakraborty to finish the teams studies in mice, so that the next person with FENIB will not have to wait as long for a potential treatment. Some of the work will be completed, and the effort could benefit others with genetic conditions that affect the brain particularly in India. We are not really trying as aggressively as we did earlier, he says. But that technology has a lot of potential.

At Uditis memorial service, Rajeev tried to make sense of the timing. Uditi was always in a hurry, he told attendees. She always had to be first. She was only a few months away from receiving an experimental treatment, but she would not wait, not even for that. She could not let science win, he said. She was always ahead.

Link:
Hope, despair and CRISPR the race to save one woman's life - Nature.com

Recommendation and review posted by Bethany Smith

More than 30,000 people in the United States alone have already received personalized CART-T-cell therapy for cancer.Credit: Qilai Shen/Bloomberg/Getty

When researchers first began to test engineered immune cells designed to fight cancer about 20 years ago, there was a scepticism. The scientific potential might be clear, but what about the economics of such a complex and specialized therapy? Each dose would have to be made afresh, with cells from an individual being shipped to a centralized laboratory, genetically engineered using sophisticated techniques and shipped back for reinfusion. The process would take too long and be too expensive. Regulators would also surely struggle to ensure the safety of such an involved, individualized process.

Today, the chatter is very different. Engineered CAR T immune cells have so far been used to treat more than 30,000 people with cancer in the United States alone. CAR-T therapy is being tested for other conditions, including some severe autoimmune disorders. As for commercial success, in 2023, CAR T cells earned biotechnology companies US$8.4 billion worldwide.

Two News Features in this issue describe other complex, bespoke therapies that, a decade ago, would have been considered infeasible, if not impossible. One is an mRNA cancer vaccine tailored to an individuals tumour genome. The other is a CRISPR-based genome-editing therapy designed but sadly never used for one young woman with a rare neurological disorder.

How personalized cancer vaccines could keep tumours from coming back

Both approaches are fraught with challenges. As in the early days of CAR-T therapy, many of them are not scientific. But by guiding regulators and developing flexible platforms for producing bespoke treatments, researchers can help to shepherd therapies to the people who need them.

Researchers have long chased after vaccines that could rally the immune system against tumours, similarly to how vaccines rouse defences against pathogens. Companies can now sequence portions of a persons tumour and select those most likely to be visible to the immune system. The mRNA molecules corresponding to those regions are synthesized, then encapsulated in fatty particles and injected much like mRNA COVID-19 vaccines. From start to finish, the process takes as little as a month.

The technology behind these cancer vaccines is clinically more advanced than the genome editing used for some more specialized applications, for which researchers do not have the luxury of running large clinical trials. In one instance, scientists knew of only one person with the mutation they aimed to treat, using a technique called base editing that can make changes to specific DNA bases. It was, in effect, a treatment designed for a market of one person.

This kind of approach is called an n-of-1 therapy, a term that highlights the statistical challenges of interpreting results from a sample of one not to mention the commercial challenge of designing and selling a therapy with a one-person market. But the name is potentially misleading and stigmatizing. A cancer vaccine based on an individuals tumour could also be considered an n-of-1 therapy, yet this approach has attracted heavy investment from the pharmaceutical industry because the same process can be extended to many other people with cancer.

Hope, despair and CRISPR the race to save one womans life

The same thinking is needed for genome-editing therapies for rare disorders. Some genetic conditions that weaken or disable the immune system could be grouped together, and therapies for these diseases designed and administered in the same manner, even if the specific DNA changes made are different. Identical or similar measures such as levels of immune-cell function could be used to determine how well the treatment works.

But for-profit companies cannot be relied on to develop such platforms for CRISPR-based therapies as long as the perceived market remains small. Some academic researchers are focusing on developing such platforms for CRISPR-based therapies. More should join them or the chance to use genome editing to correct genetic disorders, the most severe of which are often rare, will be squandered.

Researchers can help regulatory agencies grappling with the new technologies. Regulators in the United States, the European Union, India and the United Kingdom have signalled a wish to aid the development of treatments for ultra-rare disorders. But they need help. Many regulations governing the manufacturing of therapies are grounded in regulatory paths forged years ago. Scientists can advise regulators on which technological advances have rendered certain cumbersome regulations unnecessary. This could speed up the development of treatments, as well as lower their costs.

Researchers around the world can engage in the same discussions with their regulators, and not just in typical hotspots for drug development, such as the United States and Europe. Such conversations will help to prepare for a future in which bespoke genetic therapies can be produced worldwide. They could also help to harmonize regulations between countries: an important goal for promoting the development of drugs for conditions that affect only a few individuals scattered around the globe.

As data accumulate from the treatment of people with rare genetic disorders, lessons learnt about the safety, effectiveness and manufacturing of bespoke therapies can be translated to treatments for more-common conditions. So the treatment of ultra-rare genetic disorders should not be devalued. Although a single disorder might affect only a few people, in aggregate, ultra-rare diseases affect millions. When it comes to personalized medicine, serving the interests of the few is in the interests of the many.

Continued here:
CRISPR cures and cancer vaccines: researchers can help to shepherd them to market - Nature.com

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Over the past decade, CRISPR has taken the biomedical world and life sciences by storm for its ability to easily and precisely edit DNA. Here, Stanford University bioengineer Stanley Qi explains how CRISPR works, why its such an important tool, and how it could be used in the future including current developments in using CRISPR to edit the epigenome, which involves altering the chemistry of DNA instead of the DNA sequence itself.

CRISPR is not merely a tool for research. Its becoming a discipline, a driving force, and a promise that solves long-standing challenges from basic science, engineering, medicine, and the environment, said Qi, an associate professor in the Department of Bioengineering and institute scholar at Sarafan ChEM-H. Together, we can think innovatively about how to match needs with technologies to solve the most challenging problems.

(click the question to jump to the answer):

What is CRISPR

How does it work?

What are gene therapy and cell therapy, and how is CRISPR involved?

How does it differ from other gene-editing tools?

Why is it such a big deal?

How far has CRISPR technology come since it was created?

In 2019, Victoria Gray was the first person in the U.S. to receive CRISPR treatment for a genetic disease (sickle cell anemia). Now, CRISPR-based therapies are approved in the U.S. and the U.K. What is next?

Were you surprised when the 2020 Nobel Prize in chemistry went to CRISPRs developers?

Besides treatment for diseases, what are other real-world applications for CRISPR technology?

What are your views on some of the ethical concerns surrounding CRISPR?

Your group demonstrated that its possible to shrink CRISPR. Why is this significant?

What is your lab working on in terms of epigenome editing?

Are there limitations to what CRISPR can do?

What do you think CRISPR is capable of doing in the future?

How far are we from actually achieving those idealistic future goals?

The short answer: CRISPR is an immune system used by microbes to find and eliminate unwanted invaders.

Qi: CRISPR stands for clustered interspaced short palindromic repeats. Biologists use the term to describe the genetic appearance of a system that was discovered in microbes including bacteria and archaea as early as 1987. For a long time, no one really understood what it did, but around 2005, researchers discovered CRISPR is an immune system. Its used by microbes to help protect themselves from invading viruses. To stop the invaders, the microbes use CRISPR to recognize and eliminate specific trespassers.

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The short answer: When a virus or other invader enters a bacterial cell, the bacterium incorporates some of the trespassers DNA into its own genome so it can find and eliminate the virus during future infections.

Qi: Its similar to the human immune system. When a virus infects us, we generate an immune memory in the form of antibodies lots of them. Then, when the same virus infects us again, these antibodies quickly recognize the invaders and eliminate them.

When a virus infects a bacterial cell, CRISPR helps establish a memory a genetic one. The bacterium takes a piece of the viruss genome and inserts the DNA into its own genome. From that newly acquired DNA sequence, CRISPR creates a new guide RNA, a sequence that helps CRISPR find the invader via sequence complementarity (i.e., A binds to T and C binds to G). So, the next time when the virus infects that bacteria cell, the guide RNA rapidly recognizes the virus DNA sequence, binds to it, and destroys it.

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The short answer: Gene therapy can mean using CRISPR as a macromolecule drug to either fix a mutated gene or regulate a defective gene to treat a disease. Cell therapy means using CRISPR to make your bodys cells attack toxic cells or regenerate beneficial cells.

Qi: Gene therapy can mean two things: One is to fix a mutated gene, and the other is to regulate a genes expression into protein products. Our current understanding of gene therapy is still rapidly advancing, and the challenge is managing therapy safely and cheaply. Furthermore, were only looking at the simplest genetic diseases. For example, sickle cell anemia is a disease we know a lot about, and its often caused by a single mutation. So, we can configure CRISPR to fix it. But many more diseases are caused by widespread mutations, multiple mutations, and even multiple genes. In the future, gene therapy could go beyond a single mutation, and I am optimistic that in the next decades, gene therapy will become a pillar of medicine.

Cell therapy is a little different. For example, when people try to treat leukemia, a type of white blood cell tumor, sometimes chemotherapy drugs cant completely get rid of the tumor cells. In the past two decades, scientists have found that if they retrieve some of the patients T cells, which fight infections, these cells can be engineered as better fighters to recognize and eliminate tumorous cells. When the modified T cells are injected back into the patient, they can attack the tumors. However, cells are quite complicated. Sometimes, they go out of control when injected back into the patient, killing healthy cells along with the tumor cells. At other times, they may fail to work because they are suppressed by the tumor cells. CRISPR offers a powerful tool to enhance the efficacy and safety of these immune cells so that they are completely under our control for best clinical benefits.

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The short answer: CRISPR is much easier to program than other tools.

Qi: Before CRISPR, most gene-editing tools were a single protein. By changing the peptide sequence of these proteins, scientists could alter their targets. To change the target, you need to completely redesign the proteins sequence and then test if it even works, which is tedious, unpredictable, and time-consuming. These gene-editing tools were theoretically interesting, but they were difficult to use for large-scale studies and therapeutics.

Compared to that, CRISPR is elegant because the target recognition sequence is mostly encoded within an RNA rather than a protein, and redesigning this sequence is one of the simplest things you can do in molecular biology. It makes genome editing similar to operating a GPS: If you want to go to destination A, you just type the address, and to change to destination B, you just enter the new location. So, this tool dramatically reduces the burdens, cost, timing, while increasing the precision and accuracy of a gene-editing system.

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The short answer: CRISPR can precisely modify a piece of DNA or its chemistry (so-called epigenetics) in the human body, making it a potential tool for clinical uses in the biomedical sciences.

Qi: CRISPR is a molecule and tool desired by everyone who works in the life sciences, biomedical research, and clinical settings. Its high precision is unparalleled and enables many uses including gene therapy.

My dream has been to develop new biotechnologies and apply them to diseases without a cure. Genetic diseases make up a big part of this category. Traditional medicines small molecule drugs, surgery, and other methods dont work for these types of diseases. But CRISPR molecules have become highly promising as treatments because they allow us to precisely modify a piece of DNA in the human body. This could lead not only to relief but also to a cure.

Indeed, recent FDA approval of the first CRISPR drug, Casgevy, in treating sickle cell anemia and beta thalassemia speaks to its safety and potential for other diseases. Sickle cell anemia is a disease in which people have a mutation in their red blood cells. Normally, theres no treatment other than frequent blood transfusions or bone marrow transplants from a matched donor, which are expensive and damaging to a patients overall health. Using CRISPR, its possible to perform a one-time treatment to permanently correct the mutation. There are more than 8,000 genetic diseases like that, which can be potentially considered.

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The short answer: In about a decade, scientists went from wondering if this technology would even work in human cells to getting the first CRISPR drug approved uses in the clinic.

Qi: In 2010, I was working on CRISPR as a bioengineering graduate student at the University of California, Berkeley, under Adam Arkin, a synthetic biologist and bioengineer, and collaborated with Jennifer Doudna, a biochemist and structural biologist. In the early days, CRISPRs practical usefulness was not very publicly recognized. At that time, many counterarguments said CRISPR was just a bacterial system and most of these simply dont work in human cells which, to be fair, is true.

But after Jennifer Doudna and Emmanuelle Charpentier published their seminal 2012 paper on Cas9 one type of CRISPR that cuts DNA using a single protein and an engineered single guide RNA the research and published papers grew exponentially. Firstly, because its a system that everyone in the life sciences wants. Secondly, using CRISPR is super easy, flexible, and robust. Its not like other technologies that take multiple years and millions of dollars to set up CRISPR only takes a couple of weeks and a bit more than a few hundred dollars to set up now.

A lot of researchers significantly contributed to the rapid development. For example, within three years following its initial demonstration, structural biologists solved the high-resolution, three-dimensional structure of what Cas9 and other CRISPR proteins look like. Bioinformaticians have revealed many new species of Cas molecules beyond Cas9, many of which have novel functions. Biochemists engineered CRISPR to understand how fast and tightly it binds to DNA. Bioengineers, including me, engineered the proteins to make them work more efficiently and more specifically so they can work better in the human body for gene therapies. Also, clinical researchers started to use the tool to address particular diseases.

Furthermore, the applications of CRISPR went beyond gene editing. Epigenetic editing is an exciting development, although we still await clinical benefits. It was used for targeting the human 3-dimensional genome, visualizing the DNA dynamics, or even targeting another set of molecules, RNA, for gene regulation.

I dont think Im exaggerating to say that, essentially, CRISPR has been tested as a potential treatment option for every disease that we have clear knowledge about. CRISPR cant solve all of them, but because this tool is so powerful, easy to use, and so far-reaching, it has allowed everyone to combine their expertise with CRISPR.

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The short answer: This is very exciting. Future CRISPR drugs will address more incurable diseases, which provide a test case for CRISPRs efficacy and safety in different organs and patients.

Qi: Im super excited to see CRISPR becoming a drug to treat a disease as a one-time cure. When CRISPR first came out, there were concerns about whether these bacterial molecules could be used safely in humans and whether it was safe to cut and edit human DNA. While there are still questions regarding long-term effects (beyond the period of clinical trials in tested patients) it is very encouraging that CRISPR is safe and effective.

The next step is to expand the scope of CRISPR drugs. Medicine isn't made in one day. Different diseases are caused by different mechanisms. There are already more than dozens of CRISPR clinical trials for different diseases in the liver, immune cells, eyes, and muscles. Furthermore CRISPR epigenetic editing is expanding the scope of disease to treat more types of muscular dystrophy, retina disorders, and brain diseases.

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The short answer: Not at all. But I hope the award doesnt lead people to think CRISPR research is finished its still growing, and theres much more to explore in basic research, medicine, and beyond.

Qi: Im not surprised at all. Even before 2020, researchers had been discussing when the Nobel Committee would recognize CRISPR. So, when it happened, I was super excited.

Jennifer Doudna (University of California, Berkeley) and Emmanuelle Charpentier (Max Planck Unit for the Science of Pathogens) received the Nobel Prize in Chemistry only seven years after CRISPR was first reported as a molecular system for modifying the human genome.

I hope that giving the Nobel Prize to CRISPR wont give people the impression that the genome editing field is done. This is a field thats still growing in every corner of life sciences. Besides being explored as medicine in humans, it is expanding its influence in plants, microbes, and difficult-to-engineer organisms such as fungi. There are so many questions about how we can use CRISPR for safely controlling the genome, how to use it for novel and innovative research, and how to make it a clinical product that still need to be explored.

These are exciting frontiers of further increasing the safety of CRISPR-based therapies and expanding the scope of diseases treatable by this technology.

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The short answer: Some other uses are diagnostics, manufacturing, sustainability, and ecological engineering.

Qi: CRISPR can be used for diagnostics. It has been developed as a way to sensitively detect pathogens in the environment that are affecting our bodies.

There are also opportunities in manufacturing, such as making products that we care about using organisms like yeast and bacteria. Imagine that we could use CRISPR to engineer new microbes that could boost production like 10x more beer, for instance. And also, beer that tastes much better and can be catered to different peoples wants and needs.

Sustainability is also a big application for CRISPR via bioengineering. Creating sustainable, carbon-neutral methods of energy or food production is a challenge. Genome engineering may offer better manufacturing protocols through microbes that reduce greenhouse gases, plastic, and food waste.

Finally, we get to ecological engineering. For example, people are trying to eliminate certain invading or pathogenic mosquito species using CRISPR, but in my opinion, its long-term safety and impact still need careful evaluation. Other people are trying to revive extinct species. Recently, scientists announced they were trying to revive a woolly mammoth that can live in the Arctic cold.

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The short answer: My research group often thinks about the ethics of CRISPR. Some ethically questionable areas are disease prevention and eliminating pesky species, and some definite unethical areas are enhancement and creating designer babies.

Qi: The ethical side of CRISPR is something my research group thinks about every day. One of the fundamental principles of ethics is to do no harm. Sure, we want to do something great and helpful to people, but at the same time, we have to consider if were harming other people. Using that principle, we can consider a few cases.

One example is a designer baby, which is a scary topic. That is regarded as unethical because this may create a new human species. When the germ cells sperm and egg cells are edited, this not only affects that single person, but also the children that person could have in the future.

Another concern is in the division of treatment, which has three categories: cure, prevention, and enhancement. Curing someones disease is great. Prevention, which means someone is at risk of developing a problem, is a gray area. If someone has a high chance of getting an infectious disease, should we use gene therapy to permanently modify their DNA to reduce their risk? That question really depends on if we have other options. The last category enhancement is likely unethical. People talk about the possibility of targeting a gene to grow more muscle or make people smarter or better looking. But if research goes into this category, only some people may be able to afford it. This could amplify the imbalance of socioeconomic status. Another facet to consider is medical necessity. Is the therapy really necessary, or are there other ways to solve the problem through currently available drugs, diet, exercise, etc.?

Beyond medicine, some scientists may want to use CRISPR for ecological reasons, for example, eliminating mosquitoes. From my viewpoint, thats controversial because I think every species exists for a reason. If we try to eliminate mosquitoes, we might have a chain reaction that affects other life forms in the environment and can be irreversible. I hope in the future we can make this technology reversible like installing a switch so that if we make something that turns out to be less than ideal, we still have some way to reset it.

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The short answer: Its tricky to deliver CRISPR molecules into cells. Shrinking the size of the molecule helps it easily traverse inside of cells and get to its DNA target.

Qi: CRISPR is such a magic molecule, but that magic only works if CRISPR gets inside cells and touches the DNA. The question is obvious: How can we even make CRISPR get inside the cell?

Human cells are designed to resist any invading DNA. So the human body has many strategies to prevent foreign DNA from getting in.

Many delivery methods scientists used have limited power. We can use retooled viruses to deliver clinical products into cells, but they have a small capacity the Cas9 version of CRISPR usually doesnt fit inside the virus. Therefore, the currently approved CRISPR drug requires isolating patient cells, modifying them, and putting them back in. This process is costly and slow. If we want CRISPR to become a broadly useful medicine, then we need to make the molecule as small as possible.

Thats why we made this miniature CRISPR, which we call CasMINI, which is only half the size of Cas9. We also saw that it is easier to enter cells and works better than other CRISPR molecules because it can get inside more efficiently. This miniature CRISPR can revolutionize the way that we can perform editing in the body. Our hope is to address these technical barriers then test how miniature CRISPR can be delivered to different parts of the human body to treat various genetic diseases.

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The short answer: Were trying to use CRISPR to control gene function rather than editing genes to treat diseases.

Qi: Im excited about exploring how to treat diseases without modifying human DNA through epigenome editing. Its a different way of thinking about gene therapy. Unlike gene editing, epigenome editing is reversible, safer, and promising for complex diseases that can not be easily targeted by gene editing.

To enable epigenome editing, we developed the first nuclease-deactivated dCas9 in living cells, to programmably target and control gene expression, without altering the DNA sequence. For example, if a person doesnt have enough properly working proteins, we can use epigenome editing to increase the gene expression over a long term to make more proteins to compensate for this deficiency problem, thus restoring the function to normal in patients.

In other cases, someone may have a gene mutation that produces a toxic product, such as in many muscular dystrophies or neurological degenerative diseases. Rather than using CRISPR to modify DNA, we can use our epigenome editing technology to permanently silence the gene without modifying the DNA. I am excited to test this solution in the clinic as I believe this offers a safer strategy for treatment without altering DNA.

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The short answer: There are limitations to gene editing, but new technologies are trying to expand the power of CRISPR.

Qi: One major limitation is weve been using it for only 10 years. Often, time is the best test of all technologies. Only by collecting data over enough time in all scenarios will we be able to understand everything about these technologies, like how safe they are over the long term.

In testing in human subjects with patients, even though we didnt see off-target effects or immune responses, there are still question marks. We still need to constantly improve our understanding, as well as CRISPRs accuracy and precision in different human tissues and different patients, when treating a problem.

Also, right now, CRISPR is mostly used as molecular scissors to cut DNA. But sometimes, the problem genes affected function isnt caused by a DNA mutation. Sometimes, its a gene turning on or off abnormally that causes the problem. So in that case, CRISPR shouldnt be used as molecular scissors to cut DNA, but rather as a switch to restore the gene to work properly. Epigenetic editing tools can well address such challenges.

CRISPR is like a powerful hammer. But the question is: Where is the nail? What is the most suitable nail to work on? For example, as of today, we still dont know for sure which gene causes Alzheimers disease in many patients. To use CRISPR, we need to know which gene to target and which cell is the destination. We also need to know when to perform the treatment sometimes treatment can only be done in an early stage of a persons life.

Another big issue is the high costs associated with the current CRISPR medicine. How to reduce cost is a major question. Im glad that there are active conversations between academia and industrial partners to have multiple experts in the same room to come up with the best solution.

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The short answer: It could help improve the quality of life as we age, engineer useful organisms, and even serve as a universal vaccine against viruses.

Qi: Im excited by CRISPR possibly helping anti-aging, but less in the sense of making people live longer. No one can escape aging, and its a huge burden to our healthcare system and decreases the quality of life. My hope is that in the future, CRISPR isnt just being used to save lives, but also to improve the quality of life when people age.

I also hope CRISPR can become a way to engineer a lot of useful life forms. For example, there are microbes that can capture solar energy and convert it to electricity, and maybe those could be used to produce sustainable energy. Additionally, we could engineer food thats more nutritious, prevents obesity, and so on.

Another application could be vaccines. Even now, infectious diseases, like COVID-19, have dramatically changed everyones lives, which is unbelievable. So another dream is to develop cheap and safe genetic vaccines to fight all viruses, since thats their original role in bacteria. And maybe, in the future, we could receive a small dose of CRISPR that could completely kill any new virus. Its not easy, but given that this genetic system was designed as an antiviral system, theres a chance this could work.

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The short answer: Were close to some goals but may be far from some other idealistic goals.

Qi: When it comes to CRISPR and achieving those big dreams we have for it, we're at different stages. For some goals, it might feel like we're just starting out, but for others, we're getting pretty close. For example, I'm really excited about how we're starting to use CRISPR in real-life treatments for diseases, such as sickle cell anemia. This is a big step forward! I am also very excited about CRISPR epigenetic editing, a way to turn genes on or off without changing DNA sequence, which is getting ready for its big moment in clinical trials.

The reason weve come this far is thanks to a lot of people who believe in the power of safely editing our genes to make us healthier and are working hard every day to make that a reality. Its their passion and the demand for these solutions that keep pushing us forward. Im optimistic that many of the things were dreaming about with CRISPR could become real, sooner rather than later.

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What is CRISPR? A bioengineer explains | Stanford Report - Stanford University News

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As some women age, their white blood cells can lose a copy of chromosome X. A new study sheds light on the potential causes and consequences of this phenomenon.

Credit: Created by Linda Wang with Biorender.com

Researchers have identified inherited genetic variants that may predict the loss of one copy of a womans two X chromosomes as she ages, a phenomenon known as mosaic loss of chromosome X, or mLOX. These genetic variants may play a role in promoting abnormal blood cells (that have only a single copy of chromosome X) to multiply, which may lead to several health conditions, including cancer. The study, co-led by researchers at the National Cancer Institute, part of the National Institutes of Health, was published June 12, 2024, in Nature.

To better understand the causes and effects of mLOX, researchers analyzed circulating white blood cells from nearly 900,000 women across eight biobanks, of whom 12% had the condition. The researchers identified 56 common genetic variantslocated near genes associated with autoimmune diseases and cancer susceptibilitythat influenced whether mLOX developed. In addition, rare variants in a gene known as FBXO10 were associated with a doubling in the risk of mLOX.

In women with mLOX, the investigators also identified a set of inherited genetic variants on the X chromosome that were more frequently observed on the retained X chromosome than on the one that was lost. These variants could one day be used to predict which copy of the X chromosome is retained when mLOX occurs. This is important because the copy of the X chromosome with these variants may have a growth advantage that could elevate the womans risk for blood cancer.

The researchers also looked for associations of mLOX with more than 1,200 diseases and confirmed previous findings of an association with increased risk of leukemia and susceptibility to infections that cause pneumonia.

The scientists suggest that future research should focus on how mLOX interacts with other types of genetic variation and age-related changes to potentially alter disease risk.

Mitchell Machiela, Sc.D., M.P.H., Division of Cancer Epidemiology and Genetics, National Cancer Institute

Population analyses of mosaic X chromosome loss identify genetic drivers and widespread signatures of cellular selection appears June 12, 2024, in Nature.

About the National Cancer Institute (NCI):NCIleads the National Cancer Program and NIHs efforts to dramatically reduce the prevalence of cancer and improve the lives of people with cancer. NCI supports a wide range of cancer research and training extramurally through grants and contracts. NCIs intramural research program conducts innovative, transdisciplinary basic, translational, clinical, and epidemiological research on the causes of cancer, avenues for prevention, risk prediction, early detection, and treatment, including research at the NIH Clinical Centerthe worlds largest research hospital. Learn more about the intramural research done in NCIs Division of Cancer Epidemiology and Genetics. For more information about cancer, please visit the NCI website atcancer.govor call NCIs contact center at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visitnih.gov.

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New study offers clues into genetics of X chromosome loss - National Cancer Institute (.gov)

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Machiela, M. J. et al. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome. Nat. Commun. 7, 11843 (2016).

Article CAS PubMed PubMed Central ADS Google Scholar

Zekavat, S. M. et al. Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection. Nat. Med. 27, 10121024 (2021).

Article CAS PubMed PubMed Central Google Scholar

Brown, C. J. et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349, 3844 (1991).

Article CAS PubMed ADS Google Scholar

Lyon, M. F. Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190, 372373 (1961).

Article CAS PubMed ADS Google Scholar

Tukiainen, T. et al. Landscape of X chromosome inactivation across human tissues. Nature 550, 244248 (2017).

Article PubMed PubMed Central ADS Google Scholar

Busque, L. et al. Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age. Blood 88, 5965 (1996).

Article CAS PubMed Google Scholar

Gale, R. E. & Linch, D. C. Interpretation of X-chromosome inactivation patterns. Blood 84, 23762378 (1994).

Article CAS PubMed Google Scholar

Zito, A. et al. Heritability of skewed X-inactivation in female twins is tissue-specific and associated with age. Nat. Commun. 10, 5339 (2019).

Article PubMed PubMed Central ADS Google Scholar

Forsberg, L. A. et al. Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. Nat. Genet. 46, 624628 (2014).

Article CAS PubMed PubMed Central Google Scholar

Dumanski, J. P. et al. Smoking is associated with mosaic loss of chromosome Y. Science 347, 8183 (2015).

Article CAS PubMed ADS Google Scholar

Zhou, W. et al. Mosaic loss of chromosome Y is associated with common variation near TCL1A. Nat. Genet. 48, 563568 (2016).

Article CAS PubMed PubMed Central Google Scholar

Wright, D. J. et al. Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility. Nat. Genet. 49, 674679 (2017).

Article CAS PubMed PubMed Central Google Scholar

Thompson, D. J. et al. Genetic predisposition to mosaic Y chromosome loss in blood. Nature 575, 652657 (2019).

Article CAS PubMed PubMed Central Google Scholar

Loh, P. R. et al. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature 559, 350355 (2018).

Article CAS PubMed PubMed Central ADS Google Scholar

Lin, S. H. et al. Incident disease associations with mosaic chromosomal alterations on autosomes, X and Y chromosomes: insights from a phenome-wide association study in the UK Biobank. Cell Biosci.11, 111 (2021).

Article Google Scholar

Zhou, W. et al. Detectable chromosome X mosaicism in males is rarely tolerated in peripheral leukocytes. Sci. Rep. 11, 1193 (2021).

Article CAS PubMed PubMed Central Google Scholar

Sybert, V. P. & McCauley, E. Turners syndrome. N. Engl. J. Med. 351, 12271238 (2004).

Article CAS PubMed Google Scholar

Jger, N. et al. Hypermutation of the inactive X chromosome is a frequent event in cancer. Cell 155, 567581 (2013).

Article PubMed PubMed Central Google Scholar

Koren, A. & McCarroll, S. A. Random replication of the inactive X chromosome. Genome Res. 24, 6469 (2014).

Article CAS PubMed PubMed Central Google Scholar

Kessler, M. D. et al. Common and rare variant associations with clonal haematopoiesis phenotypes. Nature 612, 301309 (2022).

Article CAS PubMed PubMed Central ADS Google Scholar

Terao, C. et al. GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation. Nat. Commun. 10, 4719 (2019).

Article CAS PubMed PubMed Central ADS Google Scholar

Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508518 (2023).

Article CAS PubMed PubMed Central ADS Google Scholar

Leitsalu, L. et al. Cohort profile: Estonian biobank of the Estonian genome center, University of Tartu. Int. J. Epidemiol. 44, 11371147 (2015).

Article PubMed Google Scholar

Sudlow, C. et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).

Article PubMed PubMed Central Google Scholar

Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203209 (2018).

Article CAS PubMed PubMed Central ADS Google Scholar

Michailidou, K. et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat. Genet. 45, 353361 (2013).

Article CAS PubMed PubMed Central Google Scholar

Michailidou, K. et al. Association analysis identifies 65 new breast cancer risk loci. Nature 551, 9294 (2017).

Article CAS PubMed PubMed Central ADS Google Scholar

Gaziano, J. M. et al. Million Veteran Program: a mega-biobank to study genetic influences on health and disease. J. Clin. Epidemiol. 70, 214223 (2016).

Article PubMed Google Scholar

Hunter-Zinck, H. et al. Genotyping array design and data quality control in the Million Veteran Program. Am. J. Hum. Genet. 106, 535548 (2020).

Article CAS PubMed PubMed Central Google Scholar

Karlson, E. W., Boutin, N. T., Hoffnagle, A. G. & Allen, N. L. Building the partners healthcare biobank at partners personalized medicine: informed consent, return of research results, recruitment lessons and operational considerations. J. Pers. Med. 6, 2 (2016).

Article PubMed PubMed Central Google Scholar

Boutin, N. T. et al. The evolution of a large biobank at Mass General Brigham. J. Pers. Med. 12, 1323 (2022).

Article PubMed PubMed Central Google Scholar

Machiela, M. et al. GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas. Sci. Data 10, 25 (2023).

Article PubMed PubMed Central Google Scholar

Nagai, A. et al. Overview of the BioBank Japan project: study design and profile. J. Epidemiol. 27, S2S8 (2017).

Article PubMed PubMed Central Google Scholar

Vlasschaert, C. et al. A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic datasets. Blood 141, 22142223 (2023).

CAS PubMed PubMed Central Google Scholar

Vuckovic, D. et al. The polygenic and monogenic basis of blood traits and diseases. Cell 182, 12141231 (2020).

Article CAS PubMed PubMed Central Google Scholar

Frampton, M. et al. Variation at 3p24. 1 and 6q23. 3 influences the risk of Hodgkins lymphoma. Nat. Commun. 4, 2549 (2013).

Article PubMed ADS Google Scholar

Berndt, S. I. et al. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat. Commun. 7, 10933 (2016).

Article CAS PubMed PubMed Central ADS Google Scholar

Celik, H. et al. JARID2 functions as a tumor suppressor in myeloid neoplasms by repressing self-renewal in hematopoietic progenitor cells. Cancer Cell 34, 741756 (2018).

Article CAS PubMed PubMed Central Google Scholar

Pattabiraman, D. R. & Gonda, T. J. Role and potential for therapeutic targeting of MYB in leukemia. Leukemia 27, 269277 (2013).

Article CAS PubMed Google Scholar

Schaffner, C., Stilgenbauer, S., Rappold, G. A., Dhner, H. & Lichter, P. Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia. Blood 94, 748753 (1999).

Article CAS PubMed Google Scholar

Zenz, T. et al. TP53 mutation and survival in chronic lymphocytic leukemia. J. Clin. Oncol. 28, 44734479 (2010).

Article PubMed Google Scholar

Catalano, A. et al. The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia. Blood 110, 40734076 (2007).

Article CAS PubMed Google Scholar

Loh, P. R., Genovese, G. & McCarroll, S. A. Monogenic and polygenic inheritance become instruments for clonal selection. Nature 584, 136141 (2020).

Article CAS PubMed PubMed Central ADS Google Scholar

Luo, Y. et al. A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response. Nat. Genet. 53, 15041516 (2021).

Article CAS PubMed PubMed Central Google Scholar

Ritari, J., Koskela, S., Hyvrinen, K. & Partanen, J. HLA-disease association and pleiotropy landscape in over 235,000 Finns. Hum. Immunol. 83, 391398 (2022).

Article CAS PubMed Google Scholar

Bao, E. L. et al. Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells. Nature 586, 769775 (2020).

Article CAS PubMed PubMed Central ADS Google Scholar

Li, X. et al. Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale. Nat. Genet. 52, 969983 (2020).

Article CAS PubMed PubMed Central Google Scholar

Zhou, W. et al. SAIGE-GENE+ improves the efficiency and accuracy of set-based rare variant association tests. Nat. Genet. 54, 14661469 (2022).

Article CAS PubMed PubMed Central Google Scholar

Chiorazzi, M. et al. Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc. Natl Acad. Sci. USA 110, 39433948 (2013).

Article CAS PubMed PubMed Central ADS Google Scholar

Spielman, R. S., McGinnis, R. E. & Ewens, W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 52, 506 (1993).

CAS PubMed PubMed Central Google Scholar

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Genetic drivers and cellular selection of female mosaic X chromosome loss - Nature.com

Recommendation and review posted by Bethany Smith

Richard DiGeorge and Jo Kaur, pictured with their son Riaan DiGeorge, founded the nonprofit Riaan Research Initiative to support UMass Chan scientists quest to cure Cockayne syndrome

UMass Chan Medical School has received $2.2 million from a nonprofit patient-advocacy organization to contract with Ohio-based Andelyn Biosciences, a contract development and manufacturing organization with extensive experience in gene therapy, to manufacture clinical grade AAV9-CSA vector to treat Cockayne syndrome.

The gift from Riaan Research Initiative brings the start of clinical trials for the fatal autosomal recessive disorder one step closer.

Riaan Research Initiatives historic contribution is the largest known donation ever made toward the development of a treatment for Cockayne syndrome, according to Riaan Research Initiative.

Cockayne syndrome primarily causes mutations in genes CSA (ERCC8) and CSB (ERCC6) and leads to a failure in DNA transcription and repair processes. Impacted children often present with significant growth failure, microcephaly, vision and hearing problems, and global developmental delays. Children with the most severe form of Cockayne syndrome have a life expectancy of five to seven years. There are no approved treatments.

Were thrilled to move on to the next step of this years-long partnership with UMass Chan and are eternally grateful to our donors who have opened the doors to a better world, said Jo Kaur, founder of Riaan Research Initiative and mother of Riaan, a 4-year-old boy diagnosed with Cockayne syndrome and the inspiration behind the research. We have strong evidence of the treatments success in the preclinical phase and look forward to our collaborators manufacturing a potentially life-saving drug that can actually be given to our children.

UMass Chan and Riaan Research Initiative launched this collaboration in 2021 when the organization funded the preclinical phase of this groundbreaking program. Now that research led by Miguel Sena-Esteves, PhD, associate professor of neurology and director of the Translational Institute for Molecular Therapeutics, and Rita Batista, PhD, instructor in neurology, has demonstrated the AAV9-CSA vector efficacy in an animal model, the team is ready to move forward with toxicology studies and clinical manufacturing.

Andelyn Biosciences has been selected to manufacture the plasmids and use its AAV Curator Suspension Platform to industrialize the process, performing analytical development and process optimization, followed by toxicology manufacturing and GMP (good manufacturing practice) production.

Earlier this year, the UMass Chan research team and Riaan Research Initiative received favorable feedback from the U.S. Food and Drug Administration on their pre-Investigational New Drug submission with plans for toxicology studies and manufacturing.

Riaan Research Initiative has been an amazing partner in our journey to develop an AAV9 gene therapy for Cockayne syndrome, Dr. Sena-Esteves said. Our dream of making a difference for Cockayne patients is coming closer every day, and signing the contract with Andelyn Biosciences to make the clinical material is a major step in that direction. Developing a gene therapy for fatal pediatric neurological diseases is challenging in many ways, but together with Riaan Research Initiative we have an outstanding team to bring our program to a first-in-human gene therapy clinical trial for Cockayne syndrome.

Original post:
UMass Chan receives $2.2 million to fund gene therapy for Cockayne syndrome - UMass Medical School

Recommendation and review posted by Bethany Smith

The risk of secondary cancer after CAR-T therapy, pioneered at Penn, is less than regulators feared last year, an FDA official said Friday at cell and gene therapy conference in King of Prussia.

The FDA had announced in November that it was studying a handful of cases where patients developed lymphoma after being treated with chimeric antigen receptor T cell, CAR-T, therapies, hailed as a possible cure for some forms of blood cancer.

In January, the agency ordered the companies to put black box warnings on the six products that were part of the review.

We were pretty concerned about this when we first saw it last year, Peter Marks, who heads the FDAs Center for Biologics Evaluation and Research, said at the conference sponsored by the Sino-American Pharmaceutical Professionals Association Greater Philadelphia.

Most look to be secondary cancers affecting the T cells of patients who already have related cancers, he said.

Luckily, the majority of these, it looks like are just secondary T cell malignancies that are occurring in people who have T cell malignancies. Thats a known phenomenon, he said.

In a few cases, however, there are signs that patients developed secondary cancer in the type of white blood cells that were genetically modified as part of their treatment, Marks said. The risk is probably on the order of 1 in 10,000 people treated, he said.

That risk is orders of magnitude lower than the risk of malignancies from forms of chemotherapy that are given after cancer hasnt responded to standard treatments, Marks said during his opening keynote address at the conference, now in its third year.

About 500 people were registered for the 2024 @Philly Cell And Gene Therapy Annual Conference, a spokesperson for the conference organizers said.

READ MORE: Emily Whitehead was the first child cured of cancer with therapy from Penn. Shes back as a freshman.

Original post:
Philadelphia Cell and Gene Therapy Conference hosts FDA officials - The Philadelphia Inquirer

Recommendation and review posted by Bethany Smith

A Pfizer gene therapy for the rare muscle-wasting disease Duchenne muscular dystrophy did not help patients ability to walk or stand up in a pivotal clinical trial. The pharmaceutical giant is still weighing its next steps for the therapy, but analysts say these disappointing trial results, the latest in a series of setbacks, likely mark the end for this program.

The Phase 3 test enrolled boys ages 4 to 7 who still had the ability to walk. The trials main goal was to show an improvement in motor function compared to a placebo. Without providing specific figures, Pfizer said after Wednesdays market close that its gene therapy did not achieve this goal measured one year after treatment. Secondary goals include measuring how fast patients can run or walk for 10 meters and how quickly they can rise from the floor. On these measures, there was no significant difference between the gene therapy arm and the placebo group.

We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped, Dan Levy, Pfizers development head for Duchenne muscular dystrophy, said in a prepared statement. We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings, with the goal of ensuring that learnings from this trial can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy.

Duchenne is an inherited disorder that results in the inability to produce normal versions of dystrophin, a protein key to muscle function. Patients develop progressively worsening muscle weakness that robs them of their ability to walk. The muscle weakness eventually affects the lungs and the heart, becoming fatal.

[Paragraph updated to correct the study on dosing pause.] The Pfizer gene therapy, fordadistrogene movaparvovec, uses an engineered virus to deliver to muscle cells a mini-version of the gene that codes for dystrophin. Its clinical development path has had prior setbacks. A patient death in 2021 led to a clinical hold on tests of the therapy. Pfizer was later cleared to resume clinical trials after implementing additional safety measures. But last month, Pfizer disclosed a patient death in a Phase 2 study evaluating its Duchenne gene therapy in boys ages 2 to 3. Dosing in that study is complete. Pfizer said dosing in the crossover arm of the Phase 3 study has paused as the company continues to gather information to understand what caused the patient death in the Phase 2 test. In the latest results reported Wednesday, Pfizer said the gene therapys safety profile was manageable and adverse effects were mostly mild to moderate.

The developments unfolding for Pfizers gene therapy come as the FDA weighs whether to award full approval to Elevidys, a Duchenne gene therapy developed by Sarepta Therapeutics. Nearly a year ago, the Sarepta therapy won accelerated approval for Duchenne patients ages 4 and 5. But last fall, the company reported the failure of the Phase 3 study meant to confirm the therapys benefit and support expansion to a wider range of patients. That pivotal study evaluated patients with the same measures used for Pfizers pivotal study.

Leerink Partners analyst Joseph Schwartz draws distinctions between the two gene therapy programs. Though both failed in Phase 3, Sareptas therapy showed statistically significant improvement according to its trials secondary measures, which are more sensitive in detecting benefit, he said in a Thursday research note. Furthermore, Sareptas gene therapy does not have the safety questions overhanging the Pfizer gene therapy.

Thus, with no efficacy signals and a less-than-pristine safety profile, we see this readout as the final nail in the coffin for the program and think it is unlikely to move forward, Schwartz said.

William Blair analyst Tim Lugo said in a research note that his firm did not view Pfizers gene therapy as a real competitive threat to Sarepta due to the safety concerns throughout its development. He echoed Schwartzs comments about the Sarepta therapys ability to hit the secondary goals of its study.

We believe overall the totality of the data generated to date support the efficacy of Elevidys, the current 4- and 5-year-old label, a conversion to full approval, and a broader expansion to include older boys and into non-ambulatory patients, Lugo said. However, we believe expansion into non-ambulatory patients is more of a stretch, and we would not be surprised if these patients are excluded from the expanded label.

Sareptas Elevidys faces a June 21 target date for an FDA decision.

Photo: Dominick Reuter/AFP, via Getty Images

Read the original:
Pfizer & Sarepta Gene Therapies Both Failed Phase 3, But Analysts Expect Sarepta Will Win Approval - MedCity News

Recommendation and review posted by Bethany Smith

Expanding on his earlier podcast discussion with EPR, Dr Arun Upadhyay, Chief Scientific Officer and Head of Research & Development at Ocugen, discusses the companys promising modifier gene therapy candidates for ophthalmic disorders.

OCU400 is a modifier gene therapy aimed at treating retinitis pigmentosa and Leber congenital amaurosis (LCA).

In April 2024, Ocugen received US Food and Drug Administration (FDA) clearance to initiate the Phase III liMeliGhT clinical trial for OCU400 for retinitis pigmentosa. Shortly thereafter, the European Medicines Agency (EMA) reviewed the study design, endpoints, and planned statistical analysis, and deemed the US-based trial acceptable for a Marketing Authorisation Application (MAA). In December 2023, the FDA granted OCU400 Regenerative Medicine Advanced Therapy (RMAT) designation.

The Phase III study will include 150 participants75 with the RHO gene mutation and 75 that are gene-agnostic. In each arm, participants will be randomised 2:1 to the treatment group (2.5 x 1010 vg/eye of OCU400) and the untreated control group.

Ocugen plans to expand the OCU400 clinical trial in the second half of 2024 to include patients with LCA, contingent on favourable results from the Phase I/II study and alignment with regulatory agencies.

EPR Podcast 24 Developing modifier gene therapy Ocugen

Unlike conventional methodsmodifier gene therapyemphasises the importance of the broader biological system, potentially leading to more effective treatments.

The gene-agnostic mechanism of action for OCU400 provides hope for a larger retinitis pigmentosa patient population and demonstrates the potential to expand the range of indications for which modifier gene therapy could apply.

Unlike conventional methods that typically focus on replacing a mutated gene with a functional copy, modifier gene therapy modifies gene expression using master gene regulators. These master regulators work in a gene-agnostic way and open the possibility for the treatment of diseases caused by different gene mutations.

Modifier gene therapy triggers epigenetic mechanisms to restore homeostasis in the cellular environment and thereby structural and functional improvement in affected cells.

This pragmatic approach emphasises the importance of the broader biological system, potentially leading to more effective treatments.

OCU410 is a modifier gene therapy for the treatment of geographic atrophy, an advanced stage of dry age-related macular degeneration (dAMD). It utilises an adeno-associated virus (AAV) delivery platform for the retinal delivery of the RAR-related orphan receptor A (RORA).

The RORA protein plays a crucial role in stress and metabolism, reducing lipofuscin deposits and oxidative stress, and demonstrates anti-inflammatory properties as well as inhibiting the complement system in in vitro and in vivo studies.

Ocugen is currently enrolling patients in the Phase I/II ArMaDa clinical trial to assess the safety and efficacy of OCU410 for GA secondary to dAMD.

The ArMaDa clinical trial will assess the safety and efficacy of unilateral subretinal administration of OCU410 in subjects with GA and will be conducted in two phases.

OCU410STis a modifier gene therapy utilising an AAV delivery platform (AAV5) for the retinal delivery of the RORA gene for treating the genetic eye disorder Stargardt disease.

The GARDian clinical trial will assess the safety and efficacy of unilateral subretinal administration of OCU410ST in participants and will be conducted in two phases.

In May 2024, Ocugen announced the second cohort (medium dose) completed dosing in the dose-escalation phase. To date, six patients with Stargardt disease have been dosed in the Phase I/II clinical trial. An additional three patients will be dosed with the high dose (cohort 3) in the dose-escalation phase.

Manufacturing of AAV vectors for gene therapy presents several significant challenges, such as:

By leveraging new technologies, [gene therapy] manufacturers can overcome existing challenges, streamline production workflows, and accelerate the development and commercialisation

There has been advancement in many areas related to gene therapy manufacturing, which has played a crucial role in accelerating gene therapy manufacturing by improving efficiency across the production process. By leveraging new technologies, manufacturers can overcome existing challenges, streamline production workflows, and accelerate the development and commercialisation.

Some of these improvements include:

Biopharmaceuticals, Clinical Development, Clinical Trials, Data Analysis, DNA, Drug Development, Drug Safety, Gene therapy, Industry Insight, Research & Development (R&D), Technology, Therapeutics

Read more:
Developing and manufacturing modifier gene therapy - European Pharmaceutical Review

Recommendation and review posted by Bethany Smith

Pictured: A scientist works behind an FDA sign/Taylor Tieden for BioSpace

The FDA approved 55 new drugs and 34 cell and gene therapies in 2023.But its not always good news that companies have to deliver to their stakeholders; the year also had its fair share of Complete Response Letters.

As we embark on 2024,BioSpaceis committed to keeping you up-to-date on all the FDAs actions in thisFDA Decision Tracker.

June 10

Product: Ipsen and Genfits Iqirvo

Indication: Primary biliary cholangitis

Monday, the FDA approved the first new drug in nearly a decade for primary biliary cholangitis: Ipsen and Genfits Iqirvo. A rare liver disease, PBC affects around 100,000 people in the U.S. and can lead to liver failure.

Iqirvo is intended to be used in combination with ursodeoxycholic acid (UDCA) in adult patients who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.

The companies won accelerated approval for Iqirvo based on a reduction of alkaline phosphatase, a biochemical marker often used as a surrogate endpoint in PBC studies. Treatment with the drug demonstrated statistically significant improvements in biochemical response compared to UDCA alone, Christelle Huguet, executive vice president and head of research and development at Ipsen, said in a press release. An improvement in survival or prevention of liver decompensation events has not yet been shown, and the companies may need to run a confirmatory trial to verify Iqirvos clinical benefit.

June 10

Product: Almiralls Klisyri

Indication: Actinic keratosis

Dermatology company Almirall secured expanded approval of Klisyri for larger actinic keratosis-affected areas of the face or scalp. Klisyri can now be used to treat lesions up to 100 cm2 caused by the pre-cancerous dermatological condition, after safety and tolerability profiles were consistent with original pivotal trial results.

The new authorization for Klisyri, a microtubule inhibitor ointment, increases dosing for surface area treatment from up to 25 cm2 to up to 100 cm2, according to the companys press release.

In the same press release, Almirall Chief Scientific Officer Karl Ziegelbauer called the expanded approval a significant step forward for both patients and treating dermatologists, adding that the latter are looking for ways to treat the entire affected area to help prevent further lesion progression.

June 7

Product: Gerons Rytelo

Indication: Myelodysplastic syndromes

Geron Corporation kicked off the weekend on a high note as the FDA approval of its telomerase inhibitor Rytelo for myelodysplastic syndromes (MDS)a group of blood cancerssent the companys stock soaring more than 30%. Rytelo is specifically approved for MDS patients with transfusion-dependent anemia who do not respond to or are ineligible for the standard-of-care treatment, erythropoiesis-stimulating agents.

The approvalGerons first after 34 years in businesswas supported by data from the Phase III IMerge trial, in which patients on Rytelo had significantly higher rates of red blood cell transfusion independence over placebo for at least 24 weeks28% in the treatment arm versus 3% on placebo. For those who responded, this was sustained for a median of 1.5 years.

June 7

Product: GSKs Arexvy

Indication: Respiratory syncytial virus

People ages 5059 at an increased risk of severe outcomes from respiratory syncytial virus have a new preventative option after the FDA greenlit GSKs RSV vaccine Arexvy for this subgroup on Friday. Arexvy is indicated for the prevention of lower respiratory tract disease associated with RSV.

Fridays label expansionwhich was backed by strong immunogenicity and safety data in this populationextends the market reach for Arexvy, which became the first vaccine for RSV in May 2023, at that point intended for adults 60 and above.

GSK is also evaluating the vaccine for use in people 18-49 at increased risk of severe disease, and immunocompromised patients 18 and older.

May 31

Product: Modernas mRESVIA

Indication: Respiratory syncytial virus

Moderna has a second product on the market after the FDA approved mRESVIAformerly mRNA-1345to protect adults 60 years and older fromrespiratory syncytial virus (RSV). In a press release, Moderna CEO Stphane Bancel touted the strength and versatility of the companys mRNA platform, adding that the approval also marks the first time an mRNA vaccine has been approved for a disease other than COVID-19.

mRESVIA won approval based on the Phase III ConquerRSV trial, a global study of around 37,000 adults aged 60 or older in 22 countries, in which it displayed an efficacy rate of 83.7% against RSV lower respiratory tract disease. No serious safety concerns were identified in the trial.

May 30

Product: BMSs Breyanzi

Indication: Mantle Cell Lymphoma

After winning approval earlier this month in follicular lymphoma, Bristol Myers Squibbs Breyanzi got the FDA nod for another indication on Thursday: relapsed or refractory mantle cell lymphoma (MCL). Specifically, Breyanzi is approved for patients with MCL who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor.

The approval is backed by the results of the MCL cohort of TRANSCEND NHL 001, where treatment with Breyanzi elicited a 67.6% complete response rate in the target patient population.

Thursdays approval marks the fourth indication for Breyanzi, making it the CAR T cell therapy available to treat the broadest array of B-cell malignancies, according to BMSs press release.

May 29

Product: Eli Lillys Retevmo

Indication: RET-altered pediatric cancers

Eli Lilly won accelerated approval Wednesday for Retevmo to treat pediatric patients two years and older with RET-positive thyroid cancers and other solid tumors that carry the mutation. Retevmo is the first drug in the class available for children under 12 years of age, Pharmaphorum reported.

Retevmo is specifically indicated for advanced or metastatic medullary thyroid cancer with a RET mutation, advanced or metastatic thyroid cancer with a RET gene fusion untreatable with radioactive iodine therapy, and locally advanced or metastatic solid tumors with a RET gene fusion that have progressed after prior systemic treatment or have no treatment options, according to the publication.

The new approval for Retevmo, which was previously authorized to treat patients 12 and older with RET-positive thyroid cancers, is based on a single-arm study that showed an overall response rate of 48%, with a median duration of response not reached after 12 months of follow-up.

May 29

Product: Tris Pharmas Onyda XR

Indication: Attention deficit hyperactivity disorder

Wednesday, the FDA greenlit Tris Pharmas Onyda XR as the first non-stimulant medication for attention deficit hyperactivity disorder (ADHD) with a liquid formulation and nighttime dosing, according to the company. Onyda XR is a reformulation of clonidine hydrochloride, which was first approved by the FDA in 1974 to treat high blood pressure. Clonidine was approved for ADHD in 2010 under the brand name Kapvay, which is owned by Shionogi.

Onyda XR leverages Tris LiquiXR platform, producing a smooth, extended-release profile, per the biotech.

Approved for patients six years and older, Tris expects to have Onyda XR available in U.S. pharmacies by the second half of 2024.

May 29

Product: Tevas Austedo XR

Indication: Tardive dyskinesia and Huntingtons disease chorea

People with tardive dyskinesia and Huntingtons disease chorea have a streamlined treatment option after the FDA approved a new one-pill-a-day version of Tevas Austedo XR. The newly approved formulation offers more flexibility with the most once-daily doses of any vesicular monoamine transporter 2 (VMAT2) inhibitor, for these conditions, according to Tevas press release. Austedo XR comes in four tablet strengths: 30, 36, 42 and 48 mg.

Austedo XR, a once-daily extended-release formulation, was first approved in February 2023.

May 28

Product: Amgens Bkemv

Indication: Paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome

AstraZenecas rare disease drug Soliris now has a biosimilar on the market after the FDA greenlit Amgens Bkemv to treat paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Bkemv was granted the FDAs interchangeability designation, which allows it to be used in place of the branded reference product without needing to change the prescription.

Like Soliris, Bkemv carries a boxed warning for meningococcal infections, which according to its label can be serious and life-threatening. Thus, it is only available through a restricted Risk Evaluation and Mitigation Strategies program.

May 16

Product: Amgens Imdelltra

Indication: Small cell lung cancer

Amgen secured approval Thursday for its first-in-class bi-specific T-cell engager, Imdelltra, for extensive-stage small cell lung cancer (SCLC). With the FDA nod, Imdelltra becomes the first bispecific T-cell engager therapy for advanced SCLC.

The accelerated approval was based on a Phase II study of 99 patients in the target population, where Imdelltra led to an overall response rate of 40% and a median duration of response of 9.7 months. Imdelltras label contains a boxed warning for serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome, according to the FDAs press release.

May 15

Product: BMSs Breyanzi

Indication: Follicular lymphoma

Bristol Myers Squibbs Breyanzi is now approved for the treatment of relapsed or refractory follicular lymphoma after the FDA granted a label expansion under its accelerated approval pathway. The approval was backed by data from the Phase II TRANSCEND FL study in which treatment with the CAR T cell therapy led to a 95.7% overall response rate, with a complete response rate of 73.4%.

Breyanzi, which first won approval in February 2021 for relapsed or refractory large B cell lymphoma, is also authorized to treat small lymphocytic leukemia and chronic lymphocytic leukemia. By May 31, the FDA is expected to decide whether to grant approval for the therapy in refractory mantle cell lymphoma.

May 14

Product: Dynavaxs Heplisav-B

Indication: Hepatitis B patients undergoing hemodialysis

The FDA declined to approve the supplemental Biologics License Application for Dynavax Technologies hepatitis B vaccine in patients undergoing hemodialysis, deeming the safety and efficacy data submitted by the company insufficient.

In its Complete Response Letter, the regulator said the data was insufficient because a third-party clinical site operator destroyed data source documents for about half of the subjects enrolled in the vaccines trial, according to Reuters.

While the vaccine, Heplisav-B, initially won approval for the prevention of hepatitis B in 2017, its path to the market was rocky, with two previous rejections in 2013 and 2016 for unresolved safety concerns, per Reuters.

May 1

Product: Boehringer Ingelheims Cyltezo

Indication: Rheumatoid arthritis, Crohns disease, ulcerative colitis and more

Theres another new biosimilar option to AbbVies blockbuster antirheumatic Humira. Wednesday, the FDA greenlit a high-concentration and citrate-free version of Boehringer Ingelheims Cyltezo, which was originally approved in October 2021. The newly approved dose is 100 mg/mL and is sold at a 5% discount to the branded reference product.

Cyltezo is indicated for all the same conditions as Humira, including moderate-to-severe rheumatoid arthritis, Crohns disease and ulcerative colitis. Wednesdays approval is backed by data from the Phase I VOLTAIRE-HCLF study, which compared the bioavailability of the high- and low-concentration (50 mg/mL) formulation of Cyltezo in 200 healthy volunteers.

April 30

Product: Neurocrine Biosciences Ingrezza

Indication: Huntingtons disease

A more convenient version of Neurocrine Biosciences Ingrezza will be hitting the market to treat tardive dyskinesia and chorea in Huntingtons disease after the FDA closed out April by approving a sprinkle capsule formulation of the drug.

Like the original capsule version, which was approved in 2017 for tardive dyskinesia and in 2023 for chorea in Huntingtons, Ingrezzas sprinkle formulation comes in 40-mg, 60-mg and 80-mg doses but is designed to be opened and sprinkled on soft foods. This format could be more accessible for patients who have trouble swallowing whole capsules, according to the Neurocrines announcement, which also noted that a survey of Huntingtons patients with chorea and their caregivers showed that 62% had difficulty swallowing due to their involuntary movements.

April 29

Product: Pfizer and Genmabs Tivdak

Indication: Cervical cancer

The FDA has converted the accelerated approval of Pfizer and Genmabs Tivdak into a full nod for recurrent or metastatic cervical cancer that has progressed on or after chemotherapy.

The antibody-drug conjugate (ADC), which was originally developed under a partnership between Seagen and Genmab, was granted accelerated approval in September 2021 based on a 24% objective response rate seen in the Phase II innovaTV 204 trial.

In the Phase III innovaTV 301 study, which enrolled more than 500 patients, Tivdak significantly boosted survival versus chemotherapy. An October 2023 readout showed the ADC cut the risk of death by 30% in patients with recurrent or metastatic cervical cancer; it also reduced the risk of death or worsening disease by 33% versus chemotherapy. No new safety signals were observed.

April 29

Product: X4 Pharmaceuticals Xolremdi

Indication: WHIM Syndrome

The FDAapprovedX4 Pharmaceuticals Xolremdi Monday as the first targeted treatment for WHIM syndrome, an ultra-rare immunodeficiency disease named for its four characteristics: warts, hypogammaglobulinemia, infections and myelokathexis.

Myelokathexis is a congential disorder of the white blood cells, and Xolremdi, an oral CXCR4 antagonist, is designed to mobilize white blood cells such as neutrophils, lymphocytes and monocytes from the bone marrow into the blood to improve immune deficiencies.

In the Phase III 4WHIM trial, Xolremdi showed a 60% reduction in annualized infection rate compared to placebo; trial participants had less than one infection per year compared with 4.5 for the placebo group. Patients saw an even greater reduction with additional time on treatment.

Its an exciting time for personalized medicine, and I think WHIM is going to be a poster child for rare diseases and the ability where were at now in modern medicine to design therapies to treat underlying genetic disorders, Teresa Tarrant, an associate professor at Duke Universitys School of Medicine and lead investigator of the 4WHIM trial, told BioSpace prior to Xolremdis approval.

April 26

Read more:
FDA Greenlights First Drug in Nearly a Decade for Rare Liver Disease - BioSpace

Recommendation and review posted by Bethany Smith

Patients

We screened 316 participants for eligibility (Fig. 1). Five pediatric patients (two girls and three boys) with bilateral congenital hearing loss caused by biallelic OTOF mutations were enrolled from 14 July 2023 to 15 November 2023 (Fig. 1 and Table 1). Details of Sanger sequencing results and OTOF variant interpretation in patients are provided in Extended Data Fig. 1 and Extended Data Table 1. The average auditory brainstem response (ABR) threshold was >95dB in all patients at baseline (Table 1). None of the patients received cochlear implants before the trial. A dose of 1.51012vector genomes (vg) AAV1-hOTOF per ear, selected on the basis of the previous unilateral study11, was subsequently injected into the bilateral cochleae of the patient through the round window during a one-time operation. We have completed a 26-week assessment in patients 1, 2 and 3, and a 13-week assessment in patients 4 and 5. The study is ongoing.

Five patients were enrolled to receive binaural gene therapy and were evaluated for the primary endpoint. CI, cochlear implant.

Source data

The primary endpoint was dose-limiting toxicity, defined as hematologic toxicity grade 4, nonhematologic toxicity grade 3 or aural toxicity grade 2 within 6weeks. The grade was assessed according to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE V5.0). The dose of 1.51012vg AAV1-hOTOF was selected for bilateral treatment based on the results of the unilateral study that tested different doses11. No dose-limiting toxicity happened in five patients receiving binaural gene therapy with a dose of 1.51012vg AAV1-hOTOF per ear.

Efficacy outcomes include auditory function and speech perception. ABR, auditory steady-state response (ASSR), distortion product otoacoustic emission (DPOAE), and related questionnaires and tests were used to evaluate the auditory function, speech perception and sound source localization in patients.

At baseline, the average ABR threshold in the right (left) ear was >95dB (>95dB) in all five patients. In patient 1, the average ABR threshold in the right (left) ear was restored to 65dB (68dB) at 4weeks, 63dB (63dB) at 6weeks, 63dB (63dB) at 13weeks and 58dB (58dB) at 26weeks; the average ASSR threshold in the right (left) ear was 103dB (103dB) at baseline, and was restored to 48dB (63dB) at 4weeks, 53dB (58dB) at 6weeks, 53dB (58dB) at 13weeks and 53dB (58dB) at 26weeks (Fig. 2a). In patient 2, the average ABR threshold in the right (left) ear was >95dB (>95dB) at 4weeks, >85dB (>95dB) at 6weeks, 83dB (88dB) at 13weeks and 75dB (85dB) at 26weeks; the average ASSR threshold in the right (left) ear was 88dB (83dB) at 4weeks, 73dB (85dB) at 6weeks, 61dB (64dB) at 13weeks and 60dB (60dB) at 26weeks, compared with 79dB (81dB) at baseline (Fig. 2b). In patient 3, the average ABR threshold in the right (left) ear was restored to 63dB (63dB) at 4weeks, 63dB (60dB) at 6weeks, 60dB (58dB) at 13weeks and 55dB (50dB) at 26weeks; the average ASSR threshold in the right (left) ear was restored to 58dB (63dB) at 4weeks, 60dB (65dB) at 6weeks, 63dB (60dB) at 13weeks and 53dB (53dB) at 26weeks, compared with 100dB (100dB) at baseline (Fig. 2c). In patient 4, the average ABR threshold in the right (left) ear was >95dB (>95dB) at 4weeks, >90dB (>95dB) at 6weeks and 75dB (78dB) at 13weeks; the average ASSR threshold in the right (left) ear was restored to 95dB (95dB) at 4weeks, 85dB (85dB) at 6weeks and 63dB (60dB) at 13weeks, compared with 106dB (106dB) at baseline (Fig. 2d). In patient 5, the average ABR threshold in the right (left) ear was restored to 68dB (75dB) at 4weeks, 70dB (68dB) at 6weeks and 63dB (63dB) at 13weeks; the average ASSR threshold in the right (left) ear was restored to 68dB (71dB) at 4weeks, 60dB (65dB) at 6weeks and 60dB (63dB) at 13weeks, compared with 85dB (88dB) at baseline (Fig. 2e).

ae, The ABR and ASSR thresholds of patients 1 (a), 2 (b), 3 (c), 4 (d) and 5 (e). The arrows indicate no response even at the maximum sound intensity level. Arrows pointing left and downward, right ear; arrows pointing right and downward, left ear.

In both ears of patients 13, the signal-to-noise ratio (SNR) of DPOAE decreased at most frequencies at 4weeks and gradually recovered at the later follow-up (Extended Data Fig. 2ac). In patient 4, the SNR was stable at some frequencies at 4weeks, decreased to some extent at later follow-up and has not recovered at 13weeks (Extended Data Fig. 2d). In patient 5, the SNR decreased at some frequencies at 6weeks and recovered to some degree at 13weeks (Extended Data Fig. 2e).

In patient 1, the Meaningful Auditory Integration Scale (MAIS) and Categories of Auditory Performance (CAP) scores were 1 and 0, respectively, at baseline, and 28 and 4, respectively, at 26 weeks; the Speech Intelligibility Rating (SIR) and Meaningful Use of Speech Scale (MUSS) scores were 1 and 0, respectively, at baseline, and 1 and 7, respectively, at 26 weeks. The Speech of the Speech, Spatial, and Other Qualities of Hearing Scale for Parents (SSQ-P), the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were 0.3, 0 and 0, respectively, at baseline, and were improved to 7.8, 2.8 and 5.0, respectively, at 26weeks (Table 2). In a quiet environment, the perception of monosyllable, disyllable and sentence was all 0% at baseline and 2.0%, 1.4% and 0%, respectively, at 26weeks after treatment; ambient sound, tone, initial and final was all 0% at baseline, and 31.3%, 31.3%, 20.8% and 20.8%, respectively, at 26weeks (Extended Data Table 2). For sound source localization tests, the bilateral root mean square error (RMSE) was 92.81.1 at baseline and 40.01.7 at 26weeks; when one ear was covered, the unilateral RMSE (75.51.0) at 26weeks was worse (Extended Data Table 2). In Supplementary Video 1, patient 1 could not hear at baseline and could recognize sound 4weeks and 6weeks after injection. At 13weeks, she could speak syllables such as a, ba (father), i, u, s and ma (mother). She was able to complete the sound localization test well at 13weeks.

In patient 2, the InfantToddler MAIS (IT-MAIS) and CAP scores were 0 and 0, respectively, at baseline, and 35 and 5, respectively, at 26 weeks; the SIR and MUSS scores were 1 and 0, respectively, at baseline, and 2 and 9, respectively, at 26 weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were all 0 at baseline and 6.7, 5.3 and 8.5, respectively, at 26weeks (Table 2). In Supplementary Video 2, patient 2 could not respond to sound and music at baseline, but he was able to turn to the sound source when his name was called from the left and right of his backward side 6weeks after injection. He could dance to the music and complete some simple instructions at 15weeks, and he could say some simple words, for example, ayi (aunt) and bai (bye), and communicate with others at 26weeks.

In patient 3, the IT-MAIS or MAIS, and CAP, scores were all 0 at baseline, and 35 and 5, respectively, at 26weeks; the SIR and MUSS scores were 1 and 0, respectively, at baseline, and 2 and 15, respectively, at 26weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were all 0 at baseline, and 7.3, 8.0 and 8.5, respectively, at 26 weeks (Table 2). In Supplementary Video 3, patient 3 had no response to sound and music at baseline, but he could turn back when his name was called 3weeks after injection. At 13weeks, he was able to move his body and dance when he heard the music. He was able to say some simple words at 26weeks, such as baba (father), nainai (grandmother) and yeye (grandfather).

In patient 4, the MAIS and CAP scores were 2 and 0, respectively, at baseline, and 16 and 4, respectively, at 13weeks; the SIR and MUSS scores were 1 and 2, respectively, at baseline, and 1 and 7, respectively, at 13weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were 0.3, 0 and 0, respectively, at baseline, and 3.6, 5.8 and 4.5, respectively, at 13weeks (Table 2). In Supplementary Video 4, patient 4 had no response to sound at baseline, but she could turn back when her name was called 4weeks after injection. She could complete some instructions at 13weeks, and she could say simple words at 20weeks, for example, baba (father), mama (mother) and nainai (grandmother).

In patient 5, the IT-MAIS or MAIS, and CAP, scores were 2 and 0, respectively, at baseline, and 29 and 4, respectively, at 13weeks; the SIR and MUSS scores were 1 and 0, respectively, at baseline, and 2 and 7, respectively, at 13weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were 0.2, 0 and 0, respectively, at baseline, and 7.6, 7.2 and 6.6, respectively, at 13weeks (Table 2).

To minimize the potential inflammatory response, dexamethasone was used intravenously for 8days starting from 3days before AAV1-hOTOF bilateral injection. No serious adverse event (AE) occurred. A total of 36 AEs occurred (Table 3), including emesis (patient 1), fever (patient 2), increased lymphocyte counts (patients 14), decreased lymphocyte counts (patient 3), decreased neutrophil counts (patient 2), decreased hemoglobin levels (patients 2 and 3), increased triglyceride levels (patient 2), increased cholesterol levels (patients 25), transient reduction in fibrinogen levels (patient 3), increased creatine phosphokinase levels (patient 2), decreased haptoglobin levels (patients 1 and 5), increased lactate dehydrogenase levels (patients 25), hyperglycemia (patient 5), proteinuria (patient 1) and hematuresis (patients 1 and 4). All 36 AEs were grade 1 or 2. The most common AEs were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36), followed by increased lactate dehydrogenase levels (5 out of 36). In patient 1, emesis occurred at 2h after injection and was resolved with symptomatic treatment within 1day. In patient 2, fever (highest temperature, 38.7C) occurred at 18days and 29days after injection, with mild cough and increased lymphocyte counts, but no evidence of pneumonia or other concomitant symptoms.

In addition, the structure of the ears was observed by computed tomography and magnetic resonance imaging, showing the normality of the ear structure after injection (Extended Data Figs. 3 and 4).

Neutralizing antibodies against AAV1 were increased in all patients at 6weeks after treatment (Extended Data Table 3). Vector DNA in the blood was not detectable in any patient at 7days after treatment (Extended Data Table 3). Interferon gamma (IFN-) enzyme-linked immunosorbent spot (ELISpot) responses to AAV1 capsid peptide pools with peripheral blood mononuclear cells (PBMCs) drawn from each patient at 6weeks after AAV1-hOTOF binaural gene therapy were negative (Extended Data Fig. 5)

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Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results - Nature.com

Recommendation and review posted by Bethany Smith

Inspiration sparked by shaving

Stephan co-founded Tidal Therapeutics to help commercialize his immune-cell programming nanoparticles (acquired by Sanofi in 2022). His lab needed a new direction, and inspiration struck one morning as he watched his freshly sprayed shaving foam expand in his palm.

I thought, Let's explore foam, Stephan said. Maybe we can make a formulation of foam that is not like the foam in in our shaving foam, but something that is biocompatible, to deliver therapeutics.

The froth had properties that would be attractive in a drug-delivery vehicle. Its volume started small, but puffed up. The foam stayed where it was sprayed, and didnt slide away. These characteristics could help get a therapeutic into contact with more critical cells while also ensuring that it didnt slip away.

Trying new substances or approaches that come from things in everyday life that you wouldn't necessarily associate in medical applications is sometimes a really interesting way to drive down costs and deliver drugs more easily, Fitzgerald said. But it was definitely a little bit out of my wheelhouse.

Foam-as-medical-delivery method isnt without precedent, Stephan noted. Foam-based delivery already enhances certain applications like delivery of hemorrhoid medication and intra-uterine imaging.

But could foam enhance gene therapy?

To create a bio-compatible foam, Stephan and his team initially took inspiration from the food industry.

Cocktails, ice cream, yogurt: they know how to make things foamy, he said.

Stephan Lab members, including staff scientist Sirka Stephan, PhD, started experimenting with ingredients available from the pantry store, he said.

Importantly, these materials are dead cheap, Stephan said. Theyre available for pennies. Theyre manufactured at large scale, and because theyre already used for pharmaceutical applications like coating tablets theyre available pharmaceutical-grade.

The scientists formulated a solution of methylcellulose (a food binder) and xanthan gum (a food thickener) that, when aerated using two lab syringes, bubbles into an easy-to-apply froth.

But did it have the potential to improve gene therapy?

We started with a lot of hypotheses in terms of, could foam potentially concentrate our gene therapy, keep it more localized, and help it stay in the tissue where we wanted to adhere? Fitzgerald said. My job was to do the experiments to prove the hypotheses.

Foam has certain properties that make it an attractive drug-delivery vehicle. Its more than tightly packed air bubbles: In a foam, the bubbles are separated and surrounded by incredibly thin layers of continuous liquid, called lamellae. Active ingredients become highly concentrated in these lamellae, which allows foam to deliver highly concentrated doses of medicine to large areas, even if the total dose is small.

View original post here:
Taking a frothy risk to advance gene therapy - Fred Hutchinson Cancer Center

Recommendation and review posted by Bethany Smith

Family members noticed initial signs that their children could recognize sounds two weeks after application of the therapy.

(CN) Five children born deaf can now hear in both ears after a trial of a novel gene therapy focused on repairing a hereditary dysfunction that prevents auditory signals from reaching the brain, according to authors of a study published in the journal Nature Medicine Wednesday.

The success of the therapy in both ears demonstrates that the treatment can restore a full range of hearing functions including identifying the locations of sounds, recognizing specific sounds in noisy environments and the ability to perceive and develop speech.

The researchers used a minimally invasive surgical procedure to inject vector viruses into the inner ear. The viruses transfer genes into specialized cells that convert physical sound waves into the electrical signals that can be transmitted by nerve cells.

The new genetic material allows the cells to correctly replicate a protein that is necessary to send the converted electrical signals from the inner ear to the brain.

Family members noticed initial signs that their children could recognize sounds two weeks after application of the therapy. All the children were born deaf, four of them were between one and three years of age and the fifth participant was an 11-year-old.

At four to six weeks the children would turn to face the sound when a parent called to them from outside of their plane of view. At 13 to 15 weeks children could dance to music and form simple syllables, and at 26 weeks the children used complete words and showed more advanced communication.

Its very emotional for the whole family and even for my team, some of my students were so touched that they began to cry, said lead study author Dr. Yilai Shu, director of the Diagnoses and Treatment Center of Genetic Hearing Loss affiliated with the Eye and ENT Hospital of Fudan University in Shanghai.

The successful trials grew out of a collaboration between Shu and the studys co-senior author Zheng-Yi Chen, associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear in Boston. Shu was a student of Chens and they worked together during Shus postdoctoral fellowship at Mass Eye and Ear. Shu returned to China over a decade ago, but the two scientists continued to collaborate.

The research team conducted the trials at the Eye and ENT Hospital of Fudan in Shanghi, China.

The five children that participated have a specific genetic disorder caused by the mutation of a single gene that prevents the cells in the inner from replicating the protein otoferlin that is crucial for sound signal transmission via the nervous system.

Globally, 430 million people have some form of disabling hearing loss, according to the World Health Organization. About 26 million people were born with hearing loss and 60% of those cases are due to genetic factors, the study's authors say.

This really opens a new era in treating hearing loss because there are over 150 genes that can cause genetic deafness, Shu said.

In animal trials, the research team has shown that gene therapies are effective in treating several of these forms of genetic deafness, said Chen. The teams successful treatment of the otoferlin genetic deficiency in humans means that the other models with proven success in animals can now move into human trials.

Eventually, the researchers hope to develop gene therapies for noise and age-related deafness as well.

One of the challenges of using the viral vector gene therapy with the otoferlin gene is that the gene itself is too large for the virus to carry, said Shu. To overcome this the researchers used a new technique that involves splitting the gene in half and allowing viruses to carry each half into the cells where the gene can recombine.

This is actually a technology breakthrough, said Chen, So many genes for human diseases are also very big so this approach can be broadly applied in gene therapies to treat other diseases, not only deafness.

In January the research team published the results of a trial conducted in 2022 which successfully tested the therapy in one ear. The bilateral trial involving two ears, which has allowed for participants to recover a full range of hearing functions including ability to detect the location of sound, requires a procedure for each ear resulting in an increased dosage of the viral vector.

The researchers choose to test the therapy in one ear first because the additional dosage of the viral vector is more likely to trigger an immune response which can lead to adverse affects. All five children involved in the bilateral study recovered their hearing and the adverse affects that researchers detected such as fever or elevated white blood count were well below the safety threshold.

Chen, who is also an associate professor of OtolaryngologyHead and Neck Surgery at Harvard Medical School said that international cooperation has been important to developing the treatment and Shu agrees.

This type of research is very difficult and relies on decades of international study, Shu said.

We want to use this as an example that there is a future for this kind of collaboration, Chen said. Its not a political issue its really just for human health and a common benefit for all of us.

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Children born deaf react to sound after successful gene therapy trial - Courthouse News Service

Recommendation and review posted by Bethany Smith

The first clinical trial to administer gene therapy to both ears in one person has restored hearing function to 5 children born with a form of inherited deafness, astounding the research team..

Two of the children even gained an ability to appreciate music.

The success of the new approach is detailed in a new study published in Nature Medicine. The workbuilds on the first phase of the trial, published earlier this year, in which children were treated in a single ear.

The results from these studies are astounding, says study co-senior author Zheng-Yi Chen, an associate scientist in the Eaton-Peabody Laboratories at Massachusetts Eye and Ear in the US.

We continue to see the hearing ability of treated children dramatically progress and the new study shows added benefits of the gene therapy when administrated to both ears, including the ability for sound source localisation and improvements in speech recognition in noisy environments.

Lead author Yilai Shu, an attending doctor in otolaryngologyand an investigator at Eye and Ear, Nose, Throat hospital of Fudan University, China, says: restoring hearing in both ears of children who are born deaf can maximise the benefits of hearing recovery.

These new results show this approach holds great promise and warrants larger international trials.

The children involved in the study were born with DFNB9, which accounts for between 2 and 8% of hereditary deafness. It is caused by mutations in the OTOF gene which prevent the production of functioning otoferlin protein, which can significantly reduce sound transmission from the inner ear hair cells to hearing nerves.

Through minimally invasive surgery, Shu injected adeno-associated virus (AAV) engineered to carry and deliver functioning copies of the human OTOF transgene, into the childrens inner ears.

All 5 children were observed over a 13 or 26-week period and showed hearing recovery in both ears, with dramatic improvements in speech perception and sound localisation.

During follow-up, 36 adverse events were observed, the most common being increased white blood cell counts and increased cholesterol levels. However, there were no dose-limiting toxicity or serious adverse events.

The trial is continuing, and participant are stillbeing monitored.

The authors say their results show that the gene therapy is feasible, safe, and efficacious.

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Gene therapy restores hearing to children with inherited deafness - Cosmos

Recommendation and review posted by Bethany Smith

Visiongain has published a new report entitled Gene Therapy R&D Market Report 2024-2034: Forecasts by Disease (Cancer, Rare Diseases (Oncologic, Non-oncologic), Cardiovascular Diseases, Ophthalmic Diseases, Haematology, Neurological, Diabetes Mellitus, Other)), by Vector (Viral (Retrovirus, Adenovirus, AAV, Lentivirus, Others), Non-viral (Naked DNA, Gene Gun, Electroporation, Lipofection)), by Techniques (Gene Augmentation Therapy, Gene Replacement Therapy), by Participants (Small/Medium Pharma & Biotech, Universities & Research Institutes, Hospitals, Government & Public Bodies, Big Pharma) AND Regional and Leading National Market Analysis PLUS Analysis of Leading Companies AND COVID-19 Impact and Recovery Pattern Analysis.

The gene therapy R&D market is estimated at US$3,641.7 million in 2024 and is projected to grow at a CAGR of 29.8% during the forecast period 2024-2034.

Gene Therapy: Shaping Tomorrow's Healthcare Landscape Through Innovation and Investment

Over the past five years, gene therapy has seen a remarkable resurgence fuelled by significant strides in virology, vector and capsid architecture, and manufacturing technologies. These advancements have sparked a surge in promising outcomes, attracting the attention of biotech investors and reigniting interest in the field. This renewed enthusiasm has spurred a flurry of strategic manoeuvres among biopharma firms vying for an edge in this burgeoning market.

Recent advancements in gene therapy are grounded in a deeper comprehension of viral vectors, pivotal for delivering therapeutic genes to target cells. Refinements in vector design and capsid engineering have bolstered the efficiency, specificity, and safety of gene delivery. Concurrently, progress in manufacturing processes has bolstered the scalability and consistency of gene therapy products, enabling the production of treatments for larger patient cohorts.

The market for gene and cell therapies (CGTs) is expanding rapidly, with over 1,400 companies globally focusing on CGTs and more than 3,500 therapies in preclinical and clinical development. Presently, there are over 2,000 active clinical trials, with North America leading with 964 trials, trailed by the Asia Pacific with 848, Europe with 244, and other regions with 139 active trials. Oncology and rare diseases emerge as the primary therapeutic domains targeted by CGTs, underlining the potential to address unmet medical needs and furnish innovative treatment avenues.

Investment in the CGT sector remains robust, with venture capital financing being the primary growth catalyst. The persistent inflow of capital underscores a strong belief in scientific breakthroughs and the potential to revolutionize the treatment landscape for a spectrum of diseases, encompassing both rare and common ailments.

Despite significant progress and optimism surrounding gene therapy, the field confronts several challenges, including high treatment costs, intricate regulatory requisites, and the imperative for long-term safety and efficacy data. Tackling these obstacles demands sustained collaboration among industry stakeholders, regulatory bodies, and the scientific community.

Looking ahead, the future of gene therapy holds promise. Ongoing technological advancements, coupled with substantial investment and supportive regulatory frameworks, are poised to propel further innovations and broaden the therapeutic applications of gene therapy. As the industry matures, gene therapy stands to revolutionize the treatment paradigm for a diverse array of diseases, offering newfound hope to patients who previously faced limited or no treatment options.

Download Exclusive Sample of Report https://www.visiongain.com/report/gene-therapy-market-2024/#download_sampe_div

How has COVID-19 had a Significant Impact on the Gene Therapy R&D Market?

The COVID-19 pandemic fundamentally transformed the Gene Therapy Research and Development (R&D) market, presenting a combination of challenges and opportunities that both accelerated and impeded progress. On the positive side, the urgent demand for COVID-19 treatments and vaccines spurred technological advancements, particularly in mRNA and viral vector technologies crucial to gene therapy. This urgency drove unprecedented levels of funding, collaboration, and resource allocation, fostering innovation and expediting the translation of gene therapy concepts into clinical applications. Regulatory bodies responded by streamlining approval processes for urgent therapies, potentially benefiting future gene therapy products.

The pandemic underscored the importance of robust manufacturing and distribution networks, prompting significant investments in scaling up production capabilities for gene therapies. Conversely, the pandemic caused substantial disruptions in clinical trials, with many studies delayed or halted due to lockdowns, travel restrictions, and the prioritization of COVID-19 related research, leading to setbacks in project timelines. Supply chain interruptions also impacted the availability of critical materials and reagents, complicating R&D efforts. Despite these challenges, the pandemic highlighted gene therapy's potential to address genetic disorders and emergent viral threats, reinforcing its strategic importance. The industry's resilience and adaptability were evident in its response, suggesting that the lessons learned will strengthen future gene therapy R&D efforts.

Furthermore, the pandemic emphasized the importance of global collaboration, with international partnerships playing a crucial role in accelerating the development and distribution of new technologies. Consequently, the gene therapy market is poised for sustained growth, driven by technological advances made during the pandemic and increased recognition of the value of rapid, adaptable therapeutic development platforms. Overall, while the COVID-19 pandemic presented significant obstacles, it also served as a catalyst for innovation and structural improvements within the gene therapy R&D landscape, positioning the industry for a stronger and more agile future.

How will this Report Benefit you?

Visiongains 340-page report provides 156 tables and 192 charts/graphs. Our new study is suitable for anyone requiring commercial, in-depth analyses for the gene therapy R&D market, along with detailed segment analysis in the market. Our new study will help you evaluate the overall global and regional market for Gene Therapy R&D. Get financial analysis of the overall market and different segments including disease, vector, techniques, participants, and capture higher market share. We believe that there are strong opportunities in this fast-growing gene therapy R&D market. See how to use the existing and upcoming opportunities in this market to gain revenue benefits in the near future. Moreover, the report will help you to improve your strategic decision-making, allowing you to frame growth strategies, reinforce the analysis of other market players, and maximise the productivity of the company.

What are the Current Market Drivers?

Robust Gene Therapy Pipeline Anticipated to Boost Growth

Cell and gene therapies (CGTs) are transitioning from research labs to clinical settings, offering targeted treatments for specific diseases, unlike the broader targets of small-molecule therapies. These therapies aim to introduce healthy cells or correct genetic defects in patients, with cancer emerging as a primary focus, representing nearly half of all CGTs in clinical trials.

One promising approach is CAR-T therapy (Chimeric Antigen Receptors), which combines cell and gene therapy to combat cancer. By modifying a patient's immune cells' DNA, CAR-T therapy enhances their ability to recognize and attack cancer cells. FDA approval for two CAR-T therapies signifies their efficacy, particularly for cancer patients with limited treatment options. Continued research endeavours hold the potential to expand the availability and efficacy of these therapies across a broader spectrum of cancers.

Recent data show a notable increase in gene therapies entering Phase III trials, signalling progress and momentum in this field.

Technological Advancements Projected to Fuel Market Growth

Gene therapy, both as a cutting-edge medical technique and a burgeoning biomedical business, holds a promising future propelled by technological advancements and industry promotion. While genome editing technologies enable precise manipulation of specific genes within DNA sequences, concerns regarding off-target effects, which may inadvertently edit genes with similar sequences, pose challenges such as tumorigenicity. Despite these challenges, genome editing offers the potential for lasting genomic changes, albeit with careful consideration of safety implications.

Moreover, the market for digital bioprocessing technology is driven by the demand for reproducible, efficient, and cost-effective development of cell and gene therapies. These advancements are pivotal for realizing the commercial potential of these therapies in the coming years, enhancing market penetration, and reducing overall therapy costs. Notably, breakthroughs like the use of gold nanoparticles for gene therapy delivery by researchers at the Fred Hutchinson Cancer Research Center signify promising alternatives to conventional delivery methods, potentially revolutionizing scalability and accessibility.

CRISPR-Cas9, a transformative genome editing tool, is revolutionizing scientific research with its versatility, speed, cost-effectiveness, and accuracy compared to previous methods. Its applications span across animal research, human gene therapy, medical research, and plant science, facilitating precise gene targeting, alterations, insertions, deletions, and single base pair conversions. As breakthroughs in this field continue to unfold, the gene therapy R&D market is poised for significant growth in the forecast period.

Get Detailed ToC https://www.visiongain.com/report/gene-therapy-market-2024/

Where are the Market Opportunities?

Artificial Intelligence Can Bring Value to Gene Therapy R&D

While fully AI-generated drug discovery hasn't yet yielded approved drugs, the number of drugs in development with AI-associated platforms is steadily increasing. In 2023 alone, at least 19 drugs attributed to AI were in clinical development, with potential advancement in the clinical pipeline anticipated for 2024.

AI holds significant potential in various stages of cell and gene therapy R&D, with McKinsey & Company identifying its greatest impact in target identification, payload design optimization, and translational and clinical development. For instance, AI and machine learning (ML) enhance target selection to optimize therapeutic success.

In viral therapeutics aiming for genome editing, algorithms predicting CRISPR target sites aid in identifying genomic locations conducive to efficient editing with minimal off-target activity. For mRNA-based vaccines, AI predicts tumour epitopes for therapeutic molecule binding. Similarly, in CAR T-cell therapies, AI facilitates antigen and binding site identification, enhancing CAR design for improved activity and reduced cytotoxicity.

AI and ML models rapidly screen numerous candidates and select designs meeting desired criteria, especially when integrated into an AI-enabled closed-loop research system. This system automatically feeds initial screening results into an ML pipeline, which learns from computational features to suggest optimized payload candidates for experimentation. Experimental data then feed back into the system, perpetuating learning and closing the research loop.

In translational and clinical development, AI and ML mitigate safety risks in clinical trials by identifying translational biomarkers indicative of success, selecting appropriate patients, estimating optimal dosing, and predicting severe adverse events based on patient profiles and real-world data from similar treatments.

Facility Expansion Anticipated to Offer Lucrative Growth Prospects

The surge in clinical-stage start-ups has led to a scarcity of viral vector manufacturing capacity among contract manufacturers, upon which new gene and cell therapy companies heavily rely for early-stage development. As these firms mature into commercial entities, they often opt for in-house manufacturing to circumvent outsourcing complexities. Consequently, biotech companies are formulating growth strategies, establishing internal teams, and seeking site consultant assistance. These experts aid in the rigorous search for suitable lab and development facilities, or, increasingly, in securing new construction sites in tight real estate markets.

These internal capabilities empower gene and cell therapy companies to swiftly scale up production from clinical batches to commercial scale, even during the research and development phase. Moreover, co-locating with drug research and development operations facilitates seamless technology transfer and minimizes disruption, especially during clinical trials.

The imperative for expedited "time-to-market" underscores the focus on existing buildings, which are increasingly scarce in established biotech hubs due to market demand. These hubs offer advantages such as tailored university programs and engagement with other gene and cell therapy companies, both as competitors and potential collaborators, creating a fertile environment for talent acquisition. While cost sensitivity is paramount for all ventures, venture-funded enterprises are particularly keen on cost reduction, necessitating efforts to minimize both upfront and ongoing cash outlays.

Competitive Landscape

The major players operating in the gene therapy R&D market are Astellas Pharma Inc., American Gene Technologies, Applied Genetic, Bayer, Benitec BioPharma, Biogen, Bluebird Bio, Bristol Myers Squibb, Calimmune, Inc. (CSL Behiring), Cellectis, GenSight Biologics, Gilead Lifesciences, Inc., Novartis AG, Orchard Therapeutics, Oxford Biomedica, Pfizer, Inc., REGENXBIO Inc., Sangamo Therapeutics, Inc., Sanofi, Spark Therapeutics (Subsidiary of Roche), Takeda Pharmaceuticals, Transgene, UniQure N. V., Voyager Therapeutics, ViGeneron, GQ Bio Therapeutics GmbH, OCUGEN, INC., Taysha GTx, and Sarepta Therapeutics, Inc.. These major players operating in this market have adopted various strategies comprising M&A, investment in R&D, collaborations, partnerships, regional business expansion, and new product launch.

Recent Developments

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Gene Therapy R&D market is projected to grow at a CAGR of 29.8% by 2034: Visiongain - GlobeNewswire

Recommendation and review posted by Bethany Smith

All five children taking part in a Shanghai-led clinical trial of a gene therapy to treat congenital hearing loss showed significant restoration of hearing in both ears, researchers said on Wednesday.

Their speech function and ability to locate the sources of sound were also greatly improved, researchers from the Eye and ENT Hospital of Fudan University in Shanghai said.

It was the world's first clinical trial of a gene therapy for both ears, they said.

The children, aged between 1 and 11, all have autosomal recessive deafness 9, mainly caused by mutation of a particular gene, OTOF. The research team injected gene therapy medicine developed in its previous studies into both ears of the patients in the same session, using minimally invasive and microscopic injection methods.

"Good safety of the therapy was demonstrated during their follow-up observations, proving that the binaural gene therapy with the treatment known as AAV1-hOTOF was safe and effective," said Shu Yilai, one of the leading researchers and director of the inherited deafness diagnosis and treatment center affiliated with the Shanghai hospital.

A paper about their research, a joint effort with Harvard Medical School associate professor Zheng-Yi Chen, was published recently in the journal Nature Medicine.

There are an estimated 26 million people with congenital hearing loss worldwide, and approximately 30,000 infants are born with the condition in China each year. Experts said that 60 percent of them are related to genetic factors, which severely damage their speech, cognition and intellectual development. There is, as yet, no effective clinical therapy.

People with the OTOF mutation usually suffer from severe or even complete hearing loss and speech impairment. In China, among the infants and young children diagnosed with auditory neuropathy spectrum disorder, up to 41 percent have a mutation in the OTOF gene.

Gene therapy is widely considered by experts to be one of the most promising strategies for curing hereditary deafness. It can deliver genes with normal function directly to the inner ear through a delivery vehicle, fundamentally restoring or improving hearing for such patients, the research team said.

It began recruiting participants from China for the clinical trial to receive treatment in one ear in October 2022, and completed the treatment of the first patient outside China in December that year.

Six patients were included in the trial to receive gene therapy in one ear, and the longest follow-up time for a participant has now reached 17 months, with the young patient later able to hold daily conversations.

Shu shared the clinical trial data at the annual conference of the European Society of Gene and Cell Therapy, one of the world's most authoritative international academic conferences in the field of gene and cell therapy, in Belgium in October.

The results of the clinical research that used gene therapy in one ear were published in The Lancet in January. International peers said it could open a new era for treating hearing impairment and even more diseases through gene therapy.

The clinical trial of the gene therapy in both ears began recruiting participants in July last year.

"We took a step further to try to restore the natural ability of human hearing in both ears for the patients," Shu said. "It'll also help to restore their ability to hear three-dimensional sound, locate sound sources, and distinguish speech in the context of noise."

He shared the latest progress in the trial with experts and scholars from around the world during the annual conference of the American Society of Gene& Cell Therapy held last month in Baltimore in the United States.

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Gene therapy improves deaf children's hearing - ecns

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