‘Incredibly strong and brave’ Albury girl, 3, recovering after stem cell transplant to cure cancer – Hertfordshire Mercury
Comments(0)
An 'incredibly strong and brave' three-year-old is on the road to recovery after having a stem cell transplant to cure her rare form of cancer.
Hazel Richardson, who lives in the village of Albury near Bishop's Stortford, was diagnosed with Juvenile Myelomonocytic leukaemia (JMML) in 2015.
She had her second stem cell transplant at Great Ormond Street Hospital in September 2016 after a donor in Germany was found.
Hazel's aunt, Jemma MacFadyen said: "Hazel is such a little character, so strong and brave and cheeky. She turned three in April, but she thinks she is four.
"She was incredibly strong and brave, I think it was much harder for her parents. She was very strong.
"She was diagnosed with an incredibly rare form of leukaemia in November 2015, while her mum Alice was in Addenbrooke's Hospital having a baby.
"There did not appear to be anything that wrong with Hazel, but her mum knew that something was not right.
"She was a bit floppy and kept getting these temperatures and she also had spots on her face, which we now know is quite characteristic of JMML, but at the time did not seem like anything."
READ MORE: Cheshunt boy with cerebral palsy takes first steps after potentially life-changing 75,000 operation
Hazel had her first stem cell transplant in April of last year, but unfortunately it did not take and her disease returned.
Mrs MacFadyen explained: "The only treatment for JMML is a bone marrow transplant, or stem cell transplant as it is known now.
"Hazel had her first transplant at Great Ormond Street Hospital in April last year.
"How it works is they gave her a very strong dose of chemotherapy, then they attach a drip with the transplant.
"It did not work and quickly she began relapsing even before she left Great Ormond Street."
Fortunately the blood cancer charity Anthony Nolan managed to find Hazel another donor, one with an even higher match percentage.
Mrs Facfadyen said: "JMML is very, very rare, Addenbrooke's said they have only had six or seven patients who have had the disease.
"Anthony Nolan, who have the register for donors, found another match for Hazel. He was German and was a nine out of ten match, which was better than the first one.
"So far this one has helped. We are hopeful that this has been more successful than the first one.
"They say if it comes back it comes back quickly and very hard. So every day is a day away from where we were.
"All donors make their donations in their home countries then an Anthony Nolan courier brings the stem cells over. It is all very secretive.
"When two years elapses after the transplant you can meet with the donor, if they want to, and I think this is what the family is planning on doing."
Hazel has recently started to go to Albury Acorns pre-school, and the Furnuex Pelham Church of England School is planning to donate some of the money raised from the Felham Fayre on June 25 to Anthony Nolan.
In the future Hazel's family hopes to raise money for the charity themselves according to Mrs Macfadyen.
She said: "We definitely want to do some fundraising for Anthony Nolan, something big.
"We want to be sure and we want to now as a family that we can handle it because we have just come out of a difficult time."
NEXT STORY: Cheshunt seven-year-old comes through life-changing 75,000 operation
See the original post here:
'Incredibly strong and brave' Albury girl, 3, recovering after stem cell transplant to cure cancer - Hertfordshire Mercury
Recommendation and review posted by simmons
CytoDyn Treats First Patient with PRO 140 in Phase 2 Trial for Graft versus Host Disease – GlobeNewswire (press release)
May 17, 2017 06:00 ET | Source: CytoDyn Inc.
VANCOUVER, Washington, May 17, 2017 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTC.QB:CYDY), a biotechnology company focused on the development of new therapies for combating human immunodeficiency virus (HIV) infection, announces the treatment of the first patient in its Phase 2 clinical trial for Graft versus Host Disease (GvHD), its leading immunologic indication for PRO 140.
GvHD is a potentially life-threatening complication in patients requiring a bone marrow transplant because their immune systems have been depleted during aggressive cancer therapy for certain types of leukemia. These patients have a 40-60% one-year survival rate, with relapsed GvHD as the leading causes of death.
The multicenter, 60-patient Phase 2 trial will evaluate the safety and efficacy of PRO 140 with an equal number of patients receiving PRO 140 and placebo. The trial is supported by study data using a xeno-GvHD animal model where human bone marrow stem cells were administered to immunocompromised mice, which leads to severe GvHD culminating in death. PRO 140 at a comparable dose to that being employed in CytoDyns Phase 2 trial completely eliminated any signs of GvHD in these mice. Effects of stem cell engraftment was apparent in blood, spleen and bone marrow of the mice without signs of GvHD. This preclinical study is being submitted to the U.S. Food and Drug Administration (FDA) in support of CytoDyns Orphan Drug Designation application and publication of this data is forthcoming.
We selected the transplantation indication called GvHD as our first expansion of PRO 140 into a non-HIV clinical indication because it targets the CCR5 receptor, which is known to be an important mediator of GvHD, especially in the organ damage that is the usual cause of death, said Denis R. Burger, Ph.D., CytoDyns Chief Science Officer. We plan to explore additional opportunities to expand the clinical applications of PRO 140 to those indications where CCR5 plays an important role, namely certain autoimmune diseases and cancer.
If CytoDynreceives positive results from this Phase 2 study, the Companyexpects to file for Breakthrough Designation with the FDA to expedite the commercialization of PRO 140 for this clinical indication. As previously reported, PRO 140 is considered safe and well tolerated with negligible toxicities or side effects. The Company believes these attributes make it promising for the treatment of GvHD.
About Graft versus Host Disease GvHD occurs after a bone marrow or stem cell transplant in which an individual receives bone marrow tissue or cells from a donor, known as allogeneic transplant.The transplanted cells regard the recipient's body as foreign and attack the recipient's body. GvHD does not occur when an individual receives his or her own cells during a transplant. Before a transplant, tissue and cells from possible donors are tested to determine how closely they match the person having the transplant with GvHD is less likely to occur, or symptoms to be milder, when the match is close. The chance of GvHD can be between 30% and 40% when the donor and recipient are related and 60% to 80% when the donor and recipient are not related. There are two types of GvHD: acute and chronic. Symptoms in both acute and chronic GvHD range from mild to severe. Acute GvHD usually occurs within the firstthree months after a transplant. According to the U.S. Department of Health and Human Services, nearly 5,000 allogeneic transplants were performed in the U.S. in 2016.
About CytoDyn CytoDyn is a biotechnology company focused on the clinical development and potential commercialization of humanized monoclonal antibodies for the treatment and prevention of HIV infection. The Company has one of the leading monoclonal antibodies under development for HIV infection, PRO 140, which has completed Phase 2 clinical trials with demonstrated antiviral activity in man and is currently in Phase 3. PRO 140 blocks the HIV co-receptor CCR5 on T cells, which prevents viral entry. Clinical trial results thus far indicate that PRO 140 does not negatively affect the normal immune functions that are mediated by CCR5. Results from seven Phase 1 and Phase 2 human clinical trials have shown that PRO 140 can significantly reduce viral burden in people infected with HIV. A recent Phase 2b clinical trial demonstrated that PRO 140 can prevent viral escape in patients during several months of interruption from conventional drug therapy. CytoDyn intends to continue to develop PRO 140 as a therapeutic anti-viral agent in persons infected with HIV and to pursue non-HIV indications where CCR5 and its ligand CCL5 may be involved. For more information on the Company, please visit http://www.cytodyn.com.
About PRO 140 PRO 140 belongs to a new class of HIV/AIDS therapeutics viral-entry inhibitors that are intended to protect healthy cells from viral infection. PRO 140 is a humanized IgG4 monoclonal antibody directed against CCR5, a molecular portal that HIV uses to enter T-cells. PRO 140 blocks the predominant HIV (R5) subtype entry into T-cells by masking this required co-receptor, CCR5. Importantly, PRO 140 does not appear to interfere with the normal function of CCR5 in mediating immune responses. PRO 140 does not have agonist activity toward CCR5 but does have antagonist activity to CCL5, which is a central mediator in inflammatory diseases. PRO 140 has been the subject of seven clinical trials, each demonstrating efficacy by significantly reducing or controlling HIV viral load in human test subjects. PRO 140 has been designated a fast track product by the FDA. The PRO 140 antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements as compared to daily drug therapies currently in use.
Forward-Looking Statements This press release includes forward-looking statements and forward-looking information within the meaning of United States securities laws, including statements regarding CytoDyns current and proposed trials and studies and their results, costs and completion. These statements and information represent CytoDyns intentions, plans, expectations, and beliefs and are subject to risks, uncertainties and other factors, many beyond CytoDyns control. These factors could cause actual results to differ materially from such forward-looking statements or information. The words believe, estimate, expect, intend, attempt, anticipate, foresee, plan, and similar expressions and variations thereof identify certain of such forward-looking statements or forward-looking information, which speak only as of the date on which they are made.
CytoDyn disclaims any intention or obligation to publicly update or revise any forward-looking statements or forward-looking information, whether as a result of new information, future events or otherwise, except as required by applicable law. Readers are cautioned not to place undue reliance on these forward-looking statements or forward-looking information. While it is impossible to identify or predict all such matters, these differences may result from, among other things, the inherent uncertainty of the timing and success of and expense associated with research, development, regulatory approval, and commercialization of CytoDyns products and product candidates, including the risks that clinical trials will not commence or proceed as planned; products appearing promising in early trials will not demonstrate efficacy or safety in larger-scale trials; future clinical trial data on CytoDyns products and product candidates will be unfavorable; funding for additional clinical trials may not be available; CytoDyns products may not receive marketing approval from regulators or, if approved, may fail to gain sufficient market acceptance to justify development and commercialization costs; competing products currently on the market or in development may reduce the commercial potential of CytoDyns products; CytoDyn, its collaborators or others may identify side effects after the product is on the market; or efficacy or safety concerns regarding marketed products, whether or not scientifically justified, may lead to product recalls, withdrawals of marketing approval, reformulation of the product, additional preclinical testing or clinical trials, changes in labeling of the product, the need for additional marketing applications, or other adverse events.
CytoDyn is also subject to additional risks and uncertainties, including risks associated with the actions of its corporate, academic, and other collaborators and government regulatory agencies; risks from market forces and trends; potential product liability; intellectual property litigation; environmental and other risks; and risks that current and pending patent protection for its products may be invalid, unenforceable, or challenged or fail to provide adequate market exclusivity. There are also substantial risks arising out of CytoDyns need to raise additional capital to develop its products and satisfy its financial obligations; the highly regulated nature of its business, including government cost-containment initiatives and restrictions on third-party payments for its products; the highly competitive nature of its industry; and other factors set forth in CytoDyns Annual Report on Form 10-K for the fiscal year ended May 31, 2016 and other reports filed with the U.S. Securities and Exchange Commission.
Related Articles
Recommendation and review posted by sam
Cell potency – Wikipedia
Cell potency is a cell's ability to differentiate into other cell types.[1][2] The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell which like a continuum begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency and finally unipotency. Potency is taken from the Latin term "potens" which means "having power".
Totipotency is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells.[3] In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential. Toti comes from the Latin totus which means "entirely".
It is possible for a fully differentiated cell to return to a state of totipotency.[4] This conversion to totipotency is complex, not fully understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell, but instead into a "complex cellular variation" of totipotency.[5] Stem cells resembling totipotent blastomeres from 2-cell stage embryos can arise spontaneously in the embryonic stem cell cultures[6][7] and also can be induced to arise more frequently in vitro through down-regulation of the chromatin assembly activity of CAF-1.[8]
The human development model is one which can be used to describe how totipotent cells arise.[9] Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.[10] In the first hours after fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm), into cells of the cytotrophoblast layer or syncytiotrophoblast layer of the placenta. After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.
Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species.[11] Work with zebrafish and mammals suggest a further interplay between miRNA and RNA binding proteins (RBPs) in determining development differences.[12]
In September 2013, a team from the Spanish national Cancer Research Centre was able for the first time to make adult cells from mice retreat to the characteristics of embryonic stem cells, thereby achieving totipotency.[13]
In cell biology, pluripotency (from the Latin plurimus, meaning very many, and potens, meaning having power)[14] refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system).[15] However, cell pluripotency is a continuum, ranging from the completely pluripotent cell that can form every cell of the embryo proper, e.g., embryonic stem cells and iPSCs (see below), to the incompletely or partially pluripotent cell that can form cells of all three germ layers but that may not exhibit all the characteristics of completely pluripotent cells.
Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes and transcription factors.[16] These transcription factors play a key role in determining the state of these cells and also highlights the fact that these somatic cells do preserve the same genetic information as early embryonic cells.[17] The ability to induce cells into a pluripotent state was initially pioneered in 2006 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc;[18] this technique, called reprogramming, earned Shinya Yamanaka and John Gurdon the Nobel Prize in Physiology or Medicine 2012.[19] This was then followed in 2007 by the successful induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for the induction of mouse cells.[20] These induced cells exhibit similar traits to those of embryonic stem cells (ESCs) but do not require the use of embryos. Some of the similarities between ESCs and iPSCs include pluripotency, morphology, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, and gene expression.[21]
Epigenetic factors are also thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has been theorized that certain epigenetic factors might actually work to clear the original somatic epigenetic marks in order to acquire the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is also reorganized in iPSCs and becomes like that found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are also common which is also consistent with the state of euchromatin found in ESCs.[21]
Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. iPSCs could potentially have the same therapeutic implications and applications as ESCs but without the controversial use of embryos in the process, a topic of great bioethical debate. In fact, the induced pluripotency of somatic cells into undifferentiated iPS cells was originally hailed as the end of the controversial use of embryonic stem cells. However, iPSCs were found to be potentially tumorigenic, and, despite advances,[16] were never approved for clinical stage research in the United States. Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs,[22] hindering their use as ESCs replacements.
Additionally, it has been determined that the somatic expression of combined transcription factors can directly induce other defined somatic cell fates (transdifferentiation); researchers identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons.[23] This result challenges the terminal nature of cellular differentiation and the integrity of lineage commitment; and implies that with the proper tools, all cells are totipotent and may form all kinds of tissue.
Some of the possible medical and therapeutic uses for iPSCs derived from patients include their use in cell and tissue transplants without the risk of rejection that is commonly encountered. iPSCs can potentially replace animal models unsuitable as well as in-vitro models used for disease research.[24]
Recent findings with respect to epiblasts before and after implantation have produced proposals for classifying pluripotency into two distinct phases: "naive" and "primed".[25] The baseline stem cells commonly used in science that are referred as Embryonic stem cells (ESCs) are derived from a pre-implantation epiblast; such epiblast is able to generate the entire fetus, and one epiblast cell is able to contribute to all cell lineages if injected into another blastocyst. On the other hand, several marked differences can be observed between the pre- and post-implantation epiblasts, such as their difference in morphology, in which the epiblast after implantation changes its morphology into a cup-like shape called the "egg cylinder" as well as chromosomal alteration in which one of the X-chromosomes undergoes random inactivation in the early stage of the egg cylinder, known as X-inactivation.[26] During this development, the egg cylinder epiblast cells are systematically targeted by Fibroblast growth factors, Wnt signaling, and other inductive factors via the surrounding yolk sac and the trophoblast tissue,[27] such that they become instructively specific according to the spatial organization.[28] Another major difference that was observed, with respect to cell potency, is that post-implantation epiblast stem cells are unable to contribute to blastocyst chimeras,[29] which distinguishes them from other known pluripotent stem cells. Cell lines derived from such post-implantation epiblasts are referred to as epiblast-derived stem cells which were first derived in laboratory in 2007; it should be noted, despite their nomenclature, that both ESCs and EpiSCs are derived from epiblasts, just at difference phases of development, and that pluripotency is still intact in the post-implantation epiblast, as demonstrated by the conserved expression of Nanog, Fut4, and Oct-4 in EpiSCs,[30] until somitogenesis and can be reversed midway through induced expression of Oct-4.[31]
Multipotency describes progenitor cells which have the gene activation potential to differentiate into discrete cell types. For example, a multipotent blood stem cell is a hematopoietic celland this cell type can differentiate itself into several types of blood cell types like lymphocytes, monocytes, neutrophils, etc., but cannot differentiate into brain cells, bone cells or other non-blood cell types.
New research related to multipotent cells suggests that multipotent cells may be capable of conversion into unrelated cell types. In another case, human umbilical cord blood stem cells were converted into human neurons.[32] Research is also focusing on converting multipotent cells into pluripotent cells.[33]
Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found in cord blood,[34] adipose tissue,[35] cardiac cells,[36] bone marrow, and mesenchymal stem cells (MSCs) which are found in the third molar.[37]
MSCs may prove to be a valuable source for stem cells from molars at 810 years of age, before adult dental calcification. MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes.[38]
In biology, oligopotency is the ability of progenitor cells to differentiate into a few cell types. It is a degree of potency. Examples of oligopotent stem cells are the lymphoid or myeloid stem cells.[1] A lymphoid cell specifically, can give rise to various blood cells such as B and T cells, however, not to a different blood cell type like a red blood cell.[39] Examples of progenitor cells are vascular stem cells that have the capacity to become both endothelial or smooth muscle cells.
In cell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type. It is currently unclear if true unipotent stem cells exist. Hepatoblasts, which differentiate into hepatocytes (which constitute most of the liver) or cholangiocytes (epithelial cells of the bile duct), are bipotent.[40] A close synonym for unipotent cell is precursor cell.
More here:
Cell potency - Wikipedia
Recommendation and review posted by Bethany Smith
Engineered bone marrow could make transplants safer – Science Daily
Science Daily | Engineered bone marrow could make transplants safer Science Daily Bone marrow transplants are used to treat patients with bone marrow disease. Before a transplant, a patient is first given doses of radiation, sometimes in combination with drugs, to kill off any existing stem cells in the patient's bone marrow. This ... Engineered Bone Marrow Improves Transplant Safety Engineered bone marrow may ease transplants |
Follow this link:
Engineered bone marrow could make transplants safer - Science Daily
Recommendation and review posted by simmons
New Discovery Could Soon Replace The Painful Bone Marrow … – Wall Street Pit
Patients dealing with blood and immune disorders, especially those in the most advanced stages, often have no choice but to undergo bone marrow transplants. Ironically, even if the treatment can be life-saving, it would only work when the bone marrow cells of the recipients are completely eliminated using drugs and radiation. And this could cause serious negative side effects such as organ damage, cataracts, infertility, new cancers, and even death.
Thanks to the work of engineers at the University of California San Diego (UCSD), that kind of bone marrow transplant may soon be rendered obsolete. Rather than using a live bone marrow from a compatible donor or from the patients themselves, a synthetic bone implant will instead be used and such will not require the use of drugs that can cause all those harmful side effects.
Bone marrow is the flexible tissue inside the bones that is responsible for producing red blood cells from stem cells. If, for some reason, the bone marrow fails to do its job, the result can either be severe anemia or an impaired immune system. Whichever of these conditions arise, the most effective treatment is typically a bone marrow transplant.
To reduce the undesirable side effects caused by traditional bone marrow transplants, the UCSD team of bioengineers led by Shyni Varghese have developed a synthetic bone implant with a practical marrow that can produce its own blood cells. The implant is divided into two sections, both of which are engineered from a hydrogel matrix. The exterior layer containing calcium phosphate minerals functions as a bone, while the interior layer contains donor stem cells for bone marrow growth. The exterior layer works together with the hosts cells to assist in bone building, merging the implant with the natural structure of the body.
According to the team, they have tested their engineered implant in mice, and the tests proved successful. Specifically, they implanted the synthetic bone under the skin of mice, some of which had functional bone marrow, and some of which had defective bone marrow due to radiation.
Within a four-week observation period, the implant developed bone-like structures that didnt only have blood vessels, but also marrow that actually produced red blood cells. And after six months, the synthetic implants and the bloodstream of the mice showed a mix of blood cells from both the donor and the host. This shows that the implants can function as natural bones, with the blood cells produced by the synthetic implant naturally circulating within the hosts bloodstream without being rejected.
As promising as those results are, however, there is no guarantee that the technique will be as effective in humans. Further study will be required before it can be accepted and approved by the FDA.
Theres also the matter of the treatment only being effective on patients with non-malignant bone marrow disorders. The implant cannot do anything to stop or prevent cancerous mutation from spreading, which means when it comes to cancer patients, undergoing radiation therapy will still be required to kill off their cancer cells, before a bone marrow transplant can work.
Nevertheless, this is still considered a step forward and an exciting development, particularly for individuals suffering from blood disorders. Not only will the treatment ease their pain and distress because theyll be free of their disease; it will also keep them from suffering negative side effects.
The research was recently published in the journal PNAS.
Originally posted here:
New Discovery Could Soon Replace The Painful Bone Marrow ... - Wall Street Pit
Recommendation and review posted by Bethany Smith
It worked! Jonathan Pitre’s transplant takes root – Ottawa Citizen
Mom, we did it.
With those words, Jonathan Pitre hugged his mother, Tina Boileau, and shared his joy and relief at learning the news late Tuesday afternoon that his stem cell transplant has worked.
Blood tests revealed that all of the new white cells in his bloodstream are from his mothers donated stem cells, and contain her two telltale X chromosomes. It means his mothers donated stem cells have taken root in his bone marrow and have started to produce new blood cells.
This is the best news ever, the best Mothers Day gift, said an elated Boileau, who has remained at her sons side throughout his marathon treatment for epidermolysis bullosa, a rare and painful disease that causes his skin to blister and tear easily.
Jonathan Pitre rests in bed, his pillow with his Boston terrier, Gibson, on it close by. Tina Boileau / -
Oftentimes, doctors find a mix of white blood cells, from the donor and patient, soon after a stem cell transplant. But in Pitres case, all of the new white blood cells, 100 per cent, were donor cells.
Jon is full of me, said Boileau. He doesnt have any T-cells that are his.
Pitre, who turns 17 next month, was allowed out of his room for the first time Tuesday since his April 13 transplant when he was infused with stem cells drawn from his mothers hip bone. His infection-fighting white blood cells are now numerous enough his count hit 1.0 on Tuesday that he was allowed to emerge from medical isolation.
We celebrated our good news by going for a walk in the hallway, Boileau said.
Pitre has been in Minnesota since mid-February to undergo his second attempt at the experimental treatment pioneered by doctors at the University of Minnesota Masonic Childrens Hospital.His first transplant ended in disappointment on Thanksgiving Day last year, but the family opted to undergo a second transplant, despite its risks and hardships.
This time, wonderfully, it worked.
I just got official results: Jon is 100 per cent donor! Boileau said in a text message late Tuesday afternoon.
Offered to children and adolescents with severe EB as part of a clinical trial, the stem cell transplant is physically demanding and comes with a host of life-threatening side effects. One of those potential side effects is graft-versus-host-disease (GVHD), a complication in which the new white blood cells turn on the patients tissues and attack them as foreign.
BACKGROUND:Butterfly child dreams of the Northern Lights
Pitre has suffered infections, fevers and profound exhaustion ever since his transplant while battling to get his pain levels under control. Doctors will now be on guard for signs of GVHD.
A Grade 11 student from Russell, Pitre suffers from a rare form of EB that complicates how he moves, eats, bathes and sleeps. Many of those with severe EB die from an aggressive form of skin cancer in their 20s.
The stem cell transplant holds the potential to dramatically improve Pitres life and produce tougher skin that blisters less and heals more readily.
Link:
It worked! Jonathan Pitre's transplant takes root - Ottawa Citizen
Recommendation and review posted by sam
Stem cell transplants beneficial to mice with ALS – Life Science Daily
A new study has determined bone marrow stem cell transplants improved the motor skills and nervous system of mice with amyotrophic lateral sclerosis (ALS) by repairing damage to the blood-spinal cord barrier.
ALS is a progressive neurodegenerative disease that affects neuronal cells in the brain and the spinal cord, which send signals to control muscles throughout the body. The progressive degeneration of motor neuron cells leads to death. It is estimated more than 6,000 Americans are diagnosed with the ALS yearly.
The University of South Floridas Center of Excellence for Aging and Brain Repair study findings were published in the journal Scientific Reports, determining results of their experiment are an early step in pursuing stem cells for potential repair of the blood-spinal cord barrier, which has been identified as key in the development of ALS.
Previous studies in development of various therapeutic approaches for ALS typically used pre-symptomatic mice, Svitlana Garbuzova-Davis, leader of the research project and University of South Florida health professor, said. This is the first study advancing barrier repair that treats symptomatic mice, which more closely mirrors conditions for human patients.
Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair delaying progression of the disease and improving motor function in the mice, as well as increased motor neuron cell survival the study reported.
More here:
Stem cell transplants beneficial to mice with ALS - Life Science Daily
Recommendation and review posted by Bethany Smith
Babies From Skin Cells? Prospect Is Unsettling to Some Experts – New York Times
New York Times | Babies From Skin Cells? Prospect Is Unsettling to Some Experts New York Times But stem cell biologists say it is only a matter of time before it could be used in human reproduction opening up mind-boggling possibilities. With I.V.G., two men could have a baby that was biologically related to both of them, by using skin cells ... |
Read more from the original source:
Babies From Skin Cells? Prospect Is Unsettling to Some Experts - New York Times
Recommendation and review posted by sam
Easy DNA Editing Will Remake the World. Buckle Up – WIRED
Im sorry; your browser does not support HTML5 video in WebM with VP8 or MP4 with H.264.
Spiny grass and scraggly pines creep amid the arts-and-crafts buildings of the Asilomar Conference Grounds, 100 acres of dune where California's Monterey Peninsula hammerheads into the Pacific. It's a rugged landscape, designed to inspire people to contemplate their evolving place on Earth. So it was natural that 140 scientists gathered here in 1975 for an unprecedented conference.
They were worried about what people called recombinant DNA, the manipulation of the source code of life. It had been just 22 years since James Watson, Francis Crick, and Rosalind Franklin described what DNA wasdeoxyribonucleic acid, four different structures called bases stuck to a backbone of sugar and phosphate, in sequences thousands of bases long. DNA is what genes are made of, and genes are the basis of heredity.
Preeminent genetic researchers like David Baltimore, then at MIT, went to Asilomar to grapple with the implications of being able to decrypt and reorder genes. It was a God-like powerto plug genes from one living thing into another. Used wisely, it had the potential to save millions of lives. But the scientists also knew their creations might slip out of their control. They wanted to consider what ought to be off-limits.
By 1975, other fields of sciencelike physicswere subject to broad restrictions. Hardly anyone was allowed to work on atomic bombs, say. But biology was different. Biologists still let the winding road of research guide their steps. On occasion, regulatory bodies had acted retrospectivelyafter Nuremberg, Tuskegee, and the human radiation experiments, external enforcement entities had told biologists they weren't allowed to do that bad thing again. Asilomar, though, was about establishing prospective guidelines, a remarkably open and forward-thinking move.
At the end of the meeting, Baltimore and four other molecular biologists stayed up all night writing a consensus statement. They laid out ways to isolate potentially dangerous experiments and determined that cloning or otherwise messing with dangerous pathogens should be off-limits. A few attendees fretted about the idea of modifications of the human germ linechanges that would be passed on from one generation to the nextbut most thought that was so far off as to be unrealistic. Engineering microbes was hard enough. The rules the Asilomar scientists hoped biology would follow didn't look much further ahead than ideas and proposals already on their desks.
Earlier this year, Baltimore joined 17 other researchers for another California conference, this one at the Carneros Inn in Napa Valley. It was a feeling of dj vu, Baltimore says. There he was again, gathered with some of the smartest scientists on earth to talk about the implications of genome engineering.
The stakes, however, have changed. Everyone at the Napa meeting had access to a gene-editing technique called Crispr-Cas9. The first term is an acronym for clustered regularly interspaced short palindromic repeats, a description of the genetic basis of the method; Cas9 is the name of a protein that makes it work. Technical details aside, Crispr-Cas9 makes it easy, cheap, and fast to move genes aroundany genes, in any living thing, from bacteria to people. These are monumental moments in the history of biomedical research, Baltimore says. They don't happen every day.
Using the three-year-old technique, researchers have already reversed mutations that cause blindness, stopped cancer cells from multiplying, and made cells impervious to the virus that causes AIDS. Agronomists have rendered wheat invulnerable to killer fungi like powdery mildew, hinting at engineered staple crops that can feed a population of 9 billion on an ever-warmer planet. Bioengineers have used Crispr to alter the DNA of yeast so that it consumes plant matter and excretes ethanol, promising an end to reliance on petrochemicals. Startups devoted to Crispr have launched. International pharmaceutical and agricultural companies have spun up Crispr R&D. Two of the most powerful universities in the US are engaged in a vicious war over the basic patent. Depending on what kind of person you are, Crispr makes you see a gleaming world of the future, a Nobel medallion, or dollar signs.
The technique is revolutionary, and like all revolutions, it's perilous. Crispr goes well beyond anything the Asilomar conference discussed. It could at last allow genetics researchers to conjure everything anyone has ever worried they woulddesigner babies, invasive mutants, species-specific bioweapons, and a dozen other apocalyptic sci-fi tropes. It brings with it all-new rules for the practice of research in the life sciences. But no one knows what the rules areor who will be the first to break them.
In a way, humans were genetic engineers long before anyone knew what a gene was. They could give living things new traitssweeter kernels of corn, flatter bulldog facesthrough selective breeding. But it took time, and it didn't always pan out. By the 1930s refining nature got faster. Scientists bombarded seeds and insect eggs with x-rays, causing mutations to scatter through genomes like shrapnel. If one of hundreds of irradiated plants or insects grew up with the traits scientists desired, they bred it and tossed the rest. That's where red grapefruits came from, and most barley for modern beer.
Genome modification has become less of a crapshoot. In 2002, molecular biologists learned to delete or replace specific genes using enzymes called zinc-finger nucleases; the next-generation technique used enzymes named TALENs.
Yet the procedures were expensive and complicated. They only worked on organisms whose molecular innards had been thoroughly dissectedlike mice or fruit flies. Genome engineers went on the hunt for something better.
Scientists have used it to render wheat invulnerable to killer fungi. Such crops could feed billions of people.
As it happened, the people who found it weren't genome engineers at all. They were basic researchers, trying to unravel the origin of life by sequencing the genomes of ancient bacteria and microbes called Archaea (as in archaic), descendants of the first life on Earth. Deep amid the bases, the As, Ts, Gs, and Cs that made up those DNA sequences, microbiologists noticed recurring segments that were the same back to front and front to backpalindromes. The researchers didn't know what these segments did, but they knew they were weird. In a branding exercise only scientists could love, they named these clusters of repeating palindromes Crispr.
Then, in 2005, a microbiologist named Rodolphe Barrangou, working at a Danish food company called Danisco, spotted some of those same palindromic repeats in Streptococcus thermophilus, the bacteria that the company uses to make yogurt and cheese. Barrangou and his colleagues discovered that the unidentified stretches of DNA between Crispr's palindromes matched sequences from viruses that had infected their S. thermophilus colonies. Like most living things, bacteria get attacked by virusesin this case they're called bacteriophages, or phages for short. Barrangou's team went on to show that the segments served an important role in the bacteria's defense against the phages, a sort of immunological memory. If a phage infected a microbe whose Crispr carried its fingerprint, the bacteria could recognize the phage and fight back. Barrangou and his colleagues realized they could save their company some money by selecting S. thermophilus species with Crispr sequences that resisted common dairy viruses.
As more researchers sequenced more bacteria, they found Crisprs again and againhalf of all bacteria had them. Most Archaea did too. And even stranger, some of Crispr's sequences didn't encode the eventual manufacture of a protein, as is typical of a gene, but instead led to RNAsingle-stranded genetic material. (DNA, of course, is double-stranded.)
That pointed to a new hypothesis. Most present-day animals and plants defend themselves against viruses with structures made out of RNA. So a few researchers started to wonder if Crispr was a primordial immune system. Among the people working on that idea was Jill Banfield, a geomicrobiologist at UC Berkeley, who had found Crispr sequences in microbes she collected from acidic, 110-degree water from the defunct Iron Mountain Mine in Shasta County, California. But to figure out if she was right, she needed help.
Luckily, one of the country's best-known RNA experts, a biochemist named Jennifer Doudna, worked on the other side of campus in an office with a view of the Bay and San Francisco's skyline. It certainly wasn't what Doudna had imagined for herself as a girl growing up on the Big Island of Hawaii. She simply liked math and chemistryan affinity that took her to Harvard and then to a postdoc at the University of Colorado. That's where she made her initial important discoveries, revealing the three-dimensional structure of complex RNA molecules that could, like enzymes, catalyze chemical reactions.
The mine bacteria piqued Doudna's curiosity, but when Doudna pried Crispr apart, she didn't see anything to suggest the bacterial immune system was related to the one plants and animals use. Still, she thought the system might be adapted for diagnostic tests.
Banfield wasn't the only person to ask Doudna for help with a Crispr project. In 2011, Doudna was at an American Society for Microbiology meeting in San Juan, Puerto Rico, when an intense, dark-haired French scientist asked her if she wouldn't mind stepping outside the conference hall for a chat. This was Emmanuelle Charpentier, a microbiologist at Umea University in Sweden.
As they wandered through the alleyways of old San Juan, Charpentier explained that one of Crispr's associated proteins, named Csn1, appeared to be extraordinary. It seemed to search for specific DNA sequences in viruses and cut them apart like a microscopic multitool. Charpentier asked Doudna to help her figure out how it worked. Somehow the way she said it, I literallyI can almost feel it nowI had this chill down my back, Doudna says. When she said the mysterious Csn1 I just had this feeling, there is going to be something good here.
Back in Sweden, Charpentier kept a colony of Streptococcus pyogenes in a biohazard chamber. Few people want S. pyogenes anywhere near them. It can cause strep throat and necrotizing fasciitisflesh-eating disease. But it was the bug Charpentier worked with, and it was in S. pyogenes that she had found that mysterious yet mighty protein, now renamed Cas9. Charpentier swabbed her colony, purified its DNA, and FedExed a sample to Doudna.
Working together, Charpentiers and Doudnas teams found that Crispr made two short strands of RNA and that Cas9 latched onto them. The sequence of the RNA strands corresponded to stretches of viral DNA and could home in on those segments like a genetic GPS. And when the Crispr-Cas9 complex arrives at its destination, Cas9 does something almost magical: It changes shape, grasping the DNA and slicing it with a precise molecular scalpel.
Jennifer Doudna did early work on Crispr. Photo by: Bryan Derballa
Heres whats important: Once theyd taken that mechanism apart, Doudnas postdoc, Martin Jinek, combined the two strands of RNA into one fragmentguide RNAthat Jinek could program. He could make guide RNA with whatever genetic letters he wanted; not just from viruses but from, as far as they could tell, anything. In test tubes, the combination of Jineks guide RNA and the Cas9 protein proved to be a programmable machine for DNA cutting. Compared to TALENs and zinc-finger nucleases, this was like trading in rusty scissors for a computer-controlled laser cutter. I remember running into a few of my colleagues at Berkeley and saying we have this fantastic result, and I think its going to be really exciting for genome engineering. But I dont think they quite got it, Doudna says. They kind of humored me, saying, Oh, yeah, thats nice.
On June 28, 2012, Doudnas team published its results in Science. In the paper and in an earlier corresponding patent application, they suggest their technology could be a tool for genome engineering. It was elegant and cheap. A grad student could do it.
The finding got noticed. In the 10 years preceding 2012, 200 papers mentioned Crispr. By 2014 that number had more than tripled. Doudna and Charpentier were each recently awarded the $3 million 2015 Breakthrough Prize. Time magazine listed the duo among the 100 most influential people in the world. Nobody was just humoring Doudna anymore.
Most Wednesday afternoons, Feng Zhang, a molecular biologist at the Broad Institute of MIT and Harvard, scans the contents of Science as soon as they are posted online. In 2012, he was working with Crispr-Cas9 too. So when he saw Doudna and Charpentier's paper, did he think he'd been scooped? Not at all. I didn't feel anything, Zhang says. Our goal was to do genome editing, and this paper didn't do it. Doudna's team had cut DNA floating in a test tube, but to Zhang, if you weren't working with human cells, you were just screwing around.
That kind of seriousness is typical for Zhang. At 11, he moved from China to Des Moines, Iowa, with his parents, who are engineersone computer, one electrical. When he was 16, he got an internship at the gene therapy research institute at Iowa Methodist hospital. By the time he graduated high school he'd won multiple science awards, including third place in the Intel Science Talent Search.
When Doudna talks about her career, she dwells on her mentors; Zhang lists his personal accomplishments, starting with those high school prizes. Doudna seems intuitive and has a hands-off management style. Zhang pushes. We scheduled a video chat at 9:15 pm, and he warned me that we'd be talking data for a couple of hours. Power-nap first, he said.
If new genes that wipe out malaria also make mosquitoes go extinct, what will bats eat?
Zhang got his job at the Broad in 2011, when he was 29. Soon after starting there, he heard a speaker at a scientific advisory board meeting mention Crispr. I was bored, Zhang says, so as the researcher spoke, I just Googled it. Then he went to Miami for an epigenetics conference, but he hardly left his hotel room. Instead Zhang spent his time reading papers on Crispr and filling his notebook with sketches on ways to get Crispr and Cas9 into the human genome. That was an extremely exciting weekend, he says, smiling.
Just before Doudna's team published its discovery in Science, Zhang applied for a federal grant to study Crispr-Cas9 as a tool for genome editing. Doudna's publication shifted him into hyperspeed. He knew it would prompt others to test Crispr on genomes. And Zhang wanted to be first.
Even Doudna, for all of her equanimity, had rushed to report her finding, though she hadn't shown the system working in human cells. Frankly, when you have a result that is exciting, she says, one does not wait to publish it.
In January 2013, Zhang's team published a paper in Science showing how Crispr-Cas9 edits genes in human and mouse cells. In the same issue, Harvard geneticist George Church edited human cells with Crispr too. Doudna's team reported success in human cells that month as well, though Zhang is quick to assert that his approach cuts and repairs DNA better.
That detail matters because Zhang had asked the Broad Institute and MIT, where he holds a joint appointment, to file for a patent on his behalf. Doudna had filed her patent applicationwhich was public informationseven months earlier. But the attorney filing for Zhang checked a box on the application marked accelerate and paid a fee, usually somewhere between $2,000 and $4,000. A series of emails followed between agents at the US Patent and Trademark Office and the Broad's patent attorneys, who argued that their claim was distinct.
A little more than a year after those human-cell papers came out, Doudna was on her way to work when she got an email telling her that Zhang, the Broad Institute, and MIT had indeed been awarded the patent on Crispr-Cas9 as a method to edit genomes. I was quite surprised, she says, because we had filed our paperwork several months before he had.
The Broad win started a firefight. The University of California amended Doudna's original claim to overlap Zhang's and sent the patent office a 114-page application for an interference proceedinga hearing to determine who owns Crisprthis past April. In Europe, several parties are contesting Zhang's patent on the grounds that it lacks novelty. Zhang points to his grant application as proof that he independently came across the idea. He says he could have done what Doudna's team did in 2012, but he wanted to prove that Crispr worked within human cells. The USPTO may make its decision as soon as the end of the year.
The stakes here are high. Any company that wants to work with anything other than microbes will have to license Zhang's patent; royalties could be worth billions of dollars, and the resulting products could be worth billions more. Just by way of example: In 1983 Columbia University scientists patented a method for introducing foreign DNA into cells, called cotransformation. By the time the patents expired in 2000, they had brought in $790 million in revenue.
It's a testament to Crispr's value that despite the uncertainty over ownership, companies based on the technique keep launching. In 2011 Doudna and a student founded a company, Caribou, based on earlier Crispr patents; the University of California offered Caribou an exclusive license on the patent Doudna expected to get. Caribou uses Crispr to create industrial and research materials, potentially enzymes in laundry detergent and laboratory reagents. To focus on diseasewhere the long-term financial gain of Crispr-Cas9 will undoubtedly lieCaribou spun off another biotech company called Intellia Therapeutics and sublicensed the Crispr-Cas9 rights. Pharma giant Novartis has invested in both startups. In Switzerland, Charpentier cofounded Crispr Therapeutics. And in Cambridge, Massachusetts, Zhang, George Church, and several others founded Editas Medicine, based on licenses on the patent Zhang eventually received.
Thus far the four companies have raised at least $158 million in venture capital.
Any gene typically has just a 5050 chance of getting passed on. Either the offspring gets a copy from Mom or a copy from Dad. But in 1957 biologists found exceptions to that rule, genes that literally manipulated cell division and forced themselves into a larger number of offspring than chance alone would have allowed.
A decade ago, an evolutionary geneticist named Austin Burt proposed a sneaky way to use these selfish genes. He suggested tethering one to a separate geneone that you wanted to propagate through an entire population. If it worked, you'd be able to drive the gene into every individual in a given area. Your gene of interest graduates from public transit to a limousine in a motorcade, speeding through a population in flagrant disregard of heredity's traffic laws. Burt suggested using this gene drive to alter mosquitoes that spread malaria, which kills around a million people every year. It's a good idea. In fact, other researchers are already using other methods to modify mosquitoes to resist the Plasmodium parasite that causes malaria and to be less fertile, reducing their numbers in the wild. But engineered mosquitoes are expensive. If researchers don't keep topping up the mutants, the normals soon recapture control of the ecosystem.
Push those modifications through with a gene drive and the normal mosquitoes wouldn't stand a chance. The problem is, inserting the gene drive into the mosquitoes was impossible. Until Crispr-Cas9 came along.
Emmanuelle Charpentier did early work on Crispr. Photo by: Baerbel Schmidt
Today, behind a set of four locked and sealed doors in a lab at the Harvard School of Public Health, a special set of mosquito larvae of the African species Anopheles gambiae wriggle near the surface of shallow tubs of water. These aren't normal Anopheles, though. The lab is working on using Crispr to insert malaria-resistant gene drives into their genomes. It hasn't worked yet, but if it does well, consider this from the mosquitoes' point of view. This project isn't about reengineering one of them. It's about reengineering them all.
Kevin Esvelt, the evolutionary engineer who initiated the project, knows how serious this work is. The basic process could wipe out any species. Scientists will have to study the mosquitoes for years to make sure that the gene drives can't be passed on to other species of mosquitoes. And they want to know what happens to bats and other insect-eating predators if the drives make mosquitoes extinct. I am responsible for opening a can of worms when it comes to gene drives, Esvelt says, and that is why I try to ensure that scientists are taking precautions and showing themselves to be worthy of the public's trustmaybe we're not, but I want to do my damnedest to try.
Esvelt talked all this over with his adviserChurch, who also worked with Zhang. Together they decided to publish their gene-drive idea before it was actually successful. They wanted to lay out their precautionary measures, way beyond five nested doors. Gene drive research, they wrote, should take place in locations where the species of study isn't native, making it less likely that escapees would take root. And they also proposed a way to turn the gene drive off when an engineered individual mated with a wild counterparta genetic sunset clause. Esvelt filed for a patent on Crispr gene drives, partly, he says, to block companies that might not take the same precautions.
Within a year, and without seeing Esvelt's papers, biologists at UC San Diego had used Crispr to insert gene drives into fruit fliesthey called them mutagenic chain reactions. They had done their research in a chamber behind five doors, but the other precautions weren't there.Church said the San Diego researchers had gone a step too farbig talk from a scientist who says he plans to use Crispr to bring back an extinct woolly mammoth by deriving genes from frozen corpses and injecting them into elephant embryos. (Church says tinkering with one woolly mammoth is way less scary than messing with whole populations of rapidly reproducing insects. I'm afraid of everything, he says. I encourage people to be as creative in thinking about the unintended consequences of their work as the intended.)
Ethan Bier, who worked on the San Diego fly study, agrees that gene drives come with risks. But he points out that Esvelt's mosquitoes don't have the genetic barrier Esvelt himself advocates. (To be fair, that would defeat the purpose of a gene drive.) And the ecological barrier, he says, is nonsense. In Boston you have hot and humid summers, so sure, tropical mosquitoes may not be native, but they can certainly survive, Bier says. If a pregnant female got out, she and her progeny could reproduce in a puddle, fly to ships in the Boston Harbor, and get on a boat to Brazil.
These problems don't end with mosquitoes. One of Crispr's strengths is that it works on every living thing. That kind of power makes Doudna feel like she opened Pandora's box. Use Crispr to treat, say, Huntington's diseasea debilitating neurological disorderin the womb, when an embryo is just a ball of cells? Perhaps. But the same method could also possibly alter less medically relevant genes, like the ones that make skin wrinkle. We haven't had the time, as a community, to discuss the ethics and safety, Doudna says, and, frankly, whether there is any real clinical benefit of this versus other ways of dealing with genetic disease.
Researchers in China announced they had used Crispr to edit human embryos.
That's why she convened the meeting in Napa. All the same problems of recombinant DNA that the Asilomar attendees tried to grapple with are still theremore pressing now than ever. And if the scientists don't figure out how to handle them, some other regulatory body might. Few researchers, Baltimore included, want to see Congress making laws about science. Legislation is unforgiving, he says. Once you pass it, it is very hard to undo.
In other words, if biologists don't start thinking about ethics, the taxpayers who fund their research might do the thinking for them.
All of that only matters if every scientist is on board. A month after the Napa conference, researchers at Sun Yat-sen University in Guangzhou, China, announced they had used Crispr to edit human embryos. Specifically they were looking to correct mutations in the gene that causes beta thalassemia, a disorder that interferes with a person's ability to make healthy red blood cells.
The work wasn't successfulCrispr, it turns out, didn't target genes as well in embryos as it does in isolated cells. The Chinese researchers tried to skirt the ethical implications of their work by using nonviable embryos, which is to say they could never have been brought to term. But the work attracted attention. A month later, the US National Academy of Sciences announced that it would create a set of recommendations for scientists, policymakers, and regulatory agencies on when, if ever, embryonic engineering might be permissible. Another National Academy report will focus on gene drives. Though those recommendations don't carry the weight of law, federal funding in part determines what science gets done, and agencies that fund research around the world often abide by the academy's guidelines.
The truth is, most of what scientists want to do with Crispr is not controversial. For example, researchers once had no way to figure out why spiders have the same gene that determines the pattern of veins in the wings of flies. You could sequence the spider and see that the wing gene was in its genome, but all youd know was that it certainly wasnt designing wings. Now, with less than $100, an ordinary arachnologist can snip the wing gene out of a spider embryo and see what happens when that spider matures. If its obviousmaybe its claws fail to formyouve learned that the wing gene must have served a different purpose before insects branched off, evolutionarily, from the ancestor they shared with spiders. Pick your creature, pick your gene, and you can bet someone somewhere is giving it a go.
Academic and pharmaceutical company labs have begun to develop Crispr-based research tools, such as cancerous miceperfect for testing new chemotherapies. A team at MIT, working with Zhang, used Crispr-Cas9 to create, in just weeks, mice that inevitably get liver cancer. That kind of thing used to take more than a year. Other groups are working on ways to test drugs on cells with single-gene variations to understand why the drugs work in some cases and fail in others. Zhangs lab used the technique to learn which genetic variations make people resistant to a melanoma drug called Vemurafenib. The genes he identified may provide research targets for drug developers.
The real money is in human therapeutics. For example, labs are working on the genetics of so-called elite controllers, people who can be HIV-positive but never develop AIDS. Using Crispr, researchers can knock out a gene called CCR5, which makes a protein that helps usher HIV into cells. Youd essentially make someone an elite controller. Or you could use Crispr to target HIV directly; that begins to look a lot like a cure.
Feng Zhang was awarded the Crispr patent last year. Photo by: Matthew Monteith
Orand this idea is decades away from executionyou could figure out which genes make humans susceptible to HIV overall. Make sure they dont serve other, more vital purposes, and then fix them in an embryo. Itd grow into a person immune to the virus.
But straight-out editing of a human embryo sets off all sorts of alarms, both in terms of ethics and legality. It contravenes the policies of the US National Institutes of Health, and in spirit at least runs counter to the United Nations Universal Declaration on the Human Genome and Human Rights. (Of course, when the US government said it wouldnt fund research on human embryonic stem cells, private entities raised millions of dollars to do it themselves.) Engineered humans are a ways offbut nobody thinks theyre science fiction anymore.
Even if scientists never try to design a baby, the worries those Asilomar attendees had four decades ago now seem even more prescient. The world has changed. Genome editing started with just a few big labs putting in lots of effort, trying something 1,000 times for one or two successes, says Hank Greely, a bioethicist at Stanford. Now its something that someone with a BS and a couple thousand dollars worth of equipment can do. What was impractical is now almost everyday. Thats a big deal.
In 1975 no one was asking whether a genetically modified vegetable should be welcome in the produce aisle. No one was able to test the genes of an unborn baby, or sequence them all. Today swarms of investors are racing to bring genetically engineered creations to market. The idea of Crispr slides almost frictionlessly into modern culture.
In an odd reversal, its the scientists who are showing more fear than the civilians. When I ask Church for his most nightmarish Crispr scenario, he mutters something about weapons and then stops short. He says he hopes to take the specifics of the idea, whatever it is, to his grave. But thousands of other scientists are working on Crispr. Not all of them will be as cautious. You cant stop science from progressing, Jinek says. Science is what it is. Hes right. Science gives people power. And power is unpredictable.
Amy Maxmen (@amymaxmen) writes about science for National Geographic, Newsweek, and other publications. This is her first article for WIRED.
This article appears in the August 2015 issue.
Animation by Anthony Zazzi; Illustrations by Ben Wiseman
See original here:
Easy DNA Editing Will Remake the World. Buckle Up - WIRED
Recommendation and review posted by Bethany Smith
What is CRISPR? A Beginner’s Guide | Digital Trends
}vGo)@HJZiR=}$ N(%(4w'YUXTV./zzA2|xC?.w5I29: j+N^^^V{~'hGyjA K'_zdR?N^{WO3<5OGA{?A'c^F$'IP:WIpxusoK &Yx 8G`uf&`*="o f0$3J8D:" Rs~Sk4vO+-a KeW.r=~/&cCQ4z`GtV)bQp}:H$(pe&~?v^{7[~|Oa'K`ktC0wg?4$}7w0onlS`z)5{Q+fN9l`j>s?w-/[yp}_vX6px(?ntYFs?sl&8eqn=U+,+42_*,~3rYESo3u4q? <8 @=Z Originally posted here: What is CRISPR? A Beginner's Guide | Digital Trends Recommendation and review posted by simmons
CRISPR-Cas.org
Welcome to the CRISPR-Cas.org webpage. This website is maintained by the Joung Lab at the Massachusetts General Hospital and will provide information and links to resources for those interested in using targetable CRISPR/Cas systems for genome engineering and other applications.
CRISPR/Cas systems are used by various bacteria and archaea to mediate defense against viruses and other foreign nucleic acid. Recent work has shown that Type II CRISPR/Cas systems can be engineered to direct targeted double-stranded DNA breaks in vitro to specific sequences by using a single "guide RNA" with complementarity to the DNA target site and a Cas9 nuclease (Jinek et al., Science 2012). This targetable Cas9-based system also works efficiently in cultured human cells (Mali et al., Science 2013; Cong et al., Science 2013) and in vivo in zebrafish (Hwang and Fu et al., in press) for inducing targeted alterations into endogenous genes.
We hope that the information provided on this webpage will be helpful to those interested in using CRISPR/Cas systems for genome engineering. Note that this webpage is currently under construction and further updates will be posted in the near future. We also welcome suggestions for additional materials about CRISPR/Cas technology not yet listed on these pages.
Read the original post:
Recommendation and review posted by simmons
Synthego’s genetic toolkit aims to make CRISPR more accessible – TechCrunch
TechCrunch | Synthego's genetic toolkit aims to make CRISPR more accessible TechCrunch We hear a lot about the potential and implications of the gene-editing technique CRISPR, but it's not like just anyone can open up an app, pick a gene they don't like, and build the molecular machinery needed to snip it out. That's the goal, though ... Synthego aims to simplify CRISPR editing for genetic researchers Synthego Offers Free CRISPR Design Tool Synthego First to Offer Over 100000 Genomes in Powerful New CRISPR Software |
See the original post here:
Synthego's genetic toolkit aims to make CRISPR more accessible - TechCrunch
Recommendation and review posted by sam
Geneticists Enlist Engineered Virus and CRISPR to Battle Citrus Disease – Scientific American
Fruit farmers in the United States have long feared the arrival of harmful citrus tristeza virus to their fields. But now, this devastating pathogen could be their best hope as they battle a much worse disease that is laying waste to citrus crops across the south of the country.
The agricultural company Southern Gardens Citrus in Clewiston, Florida, applied to the US Department of Agriculture (USDA) in February for permission to use an engineered version of the citrus tristeza virus (CTV) to attack the bacterium behind citrus greening. This disease has slashed US orange production in half over the past decade, and threatens to destroy the US$3.3-billion industry entirely.
The required public comment period on the application ended last week, and the USDA will now assess the possible environmental effects of the engineered virus.
Field trials of engineered CTV are already under way. If the request is approved, it would be the first time this approach has been used commercially. It could also provide an opportunity to sidestep the regulations and public stigma attached to genetically engineered crops.
Theres a real race on right now to try to save the citrus, says Carolyn Slupsky, a food scientist at the University of California, Davis. This disease is everywhere, and its horrible.
The engineered virus is just one option being explored to tackle citrus greening. Other projects aim to edit the genome of citrus trees using CRISPRCas9 to make them more resistant to the pest, or engineer trees to express defence genes or short RNA molecules that prevent disease transmission. Local growers have also helped to fund an international project that has sequenced citrus trees to hunt for more weapons against citrus greening.
There are great scientific opportunities here, says Bryce Falk, a plant pathologist at the University of California, Davis. We need to take advantage of new technologies.
Citrus greening is caused by species from the candidate bacterial genus Candidatus Liberibacter. Spread by sap-sucking, flying insects called Asian citrus psyllids (Diaphorina citri), the bacteria cause citrus trees to make bitter, misshapen fruits that have green lower halves. The disease is also widely known by its Chinese name, huanglongbing.
The first tree in the United States with symptoms was reported in Miami in 2005. We had the uh-oh moment, says Fred Gmitter, who breeds new citrus varieties at the University of Florida in Lake Alfred.
Some researchers have had accidental success against the disease. Gmitters team released a mandarin variety called Sugarbell just as the outbreak was getting under way. Although those trees have since become infected with C.Liberibacter, farmers are able to reap a reasonable crop of sweet oranges if the plants receive proper pruning and nutrition. But it is difficult to build on that success: why the trees are relatively tolerant of the disease remains a mystery.
For years, Southern Gardens Citrus has been genetically engineering plants to express genes taken from spinach that defend against the disease. The company says that the results of field trials suggest some degree of protection. But this approach will take many years to meet regulatory requirements for marketing a genetically modified crop. And consumers may not take kindly to a fruit or juice that comes from a genetically modified tree.
So Southern Gardens Citrus added a different approach, and began the USDA approval process for engineered CTV in February. Instead of modifying the trees, the company wants to alter the genome of a harmless strain of CTV so that it produces the spinach defence gene. The company intends to graft tree limbs infected with the virus onto trees. In April, the USDA announced it would start work on an environmental impact statement, a process that typically takes about two years and will be needed before the department allows the modified virus to be used commercially.
Because the virus does not alter the fruit, this approach may allow farmers to argue that the oranges are not genetically modified, and so avoid regulation and reduce public doubt.
That is also the goal of separate projects looking for genes that confer disease resistance when switched off. If researchers can find such genes, they could use CRISPR to inactivate them. Nian Wang, a plant pathologist also at the University of Florida, is using this approach to edit orange trees, and hopes to know by 2019 whether they are disease-resistant. Others are using RNA interference in psyllids to switch off genes that allow the insects to transmit the bacteria.
For now, one question dominates: whether the citrus industry will still be alive by the time these solutions make it to the groves. Its an incredibly devastating disease, says Gmitter. Growers needed answers ten years ago.
This article is reproduced with permission and wasfirst publishedon May 16, 2017.
Read the original:
Geneticists Enlist Engineered Virus and CRISPR to Battle Citrus Disease - Scientific American
Recommendation and review posted by Bethany Smith
Editas delays IND for Allergan-partnered CRISPR program – FierceBiotech
Editas Medicine has delayed the target date for filing an IND for its lead candidate. The setback to the Allergan-partnered CRISPR program stems from delays at a third-party manufacturer working on Leber congenital amaurosis treatment LCA10.
Cambridge, Massachusetts-based Editas had planned to file an IND for LCA10 by the end of the year. Now Editas has delayed that major moment in its short history and that of the broader CRISPR field until the middle of next year. The delay stems from a misstep in the production of a material used in the manufacture of the adeno-associated viral (AAV) vectors Editas will use to deliver its gene editing payloads.
AAV manufacturing requires several steps to happen in perfect sequence for things to all come together. And were using several external contractors to perform these steps. We have to produce the input material that all comes together to then create the AAV in a cell culture systems, Editas CTO Vic Meyer told investors.
In our case, one of the input materials failed a quality specification and we needed to go back and remake that material. That delay in remaking the material caused us to miss the manufacturing slot with the AAV CMO and that combined with the remaking material pushed out the timeline.
The delay will potentially see Editas fall behind CRISPR Therapeutics and Intellia Therapeutics in the race to bring a CRISPR asset to the clinic. CRISPR expects to file for clearance to test its lead beta-thalassemia candidate in Europe by the end of the year. And Intellia is on track to generate the preclinical package it needs to support a FDA nod for a study of its transthyretin therapeutic by early 2018.
Shares in Editas slipped 6% in after-hours trading following the release of news of the delay. But management is seeking to spin the setback as hiding a silver lining for the longer-term prospects of the program.
It does create a window of opportunity to incorporate elements of Allergans ophthalmology preclinical development and manufacturing expertise into the program, Editas CEO Katrine Bosley said on a conference call with investors to discuss the company's first quarter results.
Editas brought Allergan on board in March, in part to tap into the ophthalmology expertise of the larger company. Allergan paid $90 million to secure an option on fiveprograms, including the lead LCA10 candidate.
See more here:
Editas delays IND for Allergan-partnered CRISPR program - FierceBiotech
Recommendation and review posted by sam
Caribou Bioscience’s CEO on CRISPR’s legal and ethical challenges – TechCrunch
TechCrunch | Caribou Bioscience's CEO on CRISPR's legal and ethical challenges TechCrunch Caribou Bioscience co-founder and CEO Rachel Haurwitz joined us onstage at Disrupt this morning to help unpack some of the myriad complexities around her company's pioneering work in the field of CRISPR biology. The gene editing tool has been the ... |
Continue reading here:
Caribou Bioscience's CEO on CRISPR's legal and ethical challenges - TechCrunch
Recommendation and review posted by simmons
Cut Out the Hype: Gene Editing With CRISPR and the Truth about Superhuman ‘Designer Babies’ – WhatIsEpigenetics.com (blog)
Stories about a mysterious tool that can cut out and replace genes have crept out from behind the lab walls and entered boldly into the public spotlight. Nowadays, CRISPR is everywhere. And we cant help but let our imaginations wander, especially when the questions posed by this novel gene editing technology come straight out of a sci-fi movie.
Can we edit out bad genes that cause diseases in humans and replace them with healthy ones? Might parents be able to design babies to their liking, with a certain hair or eye color, personality, or intelligence level? Could we engineer animals so they cant pass on deadly diseases to us? Can we even add or remove epigenetic marks on genes of our choice to control the expression of lifes code and, perhaps, our very behavior?
The precise power of the CRISPR-Cas9 system has created exciting yet controversial opportunities for genetic and epigenetic editing. Although we certainly dont have all the answers, the intriguing questions require further exploration and a deeper look into the near and distant possibilities for our society. As endless as the opportunities may appear to scientists and laypeople alike, some are more realistic than others. Its crucial we trim the hype from the realistic capabilities of CRISPR, as we usher in what some may call the golden age of genetic engineering.
The start of CRISPR
You know when you pick up a suspense novel, and read the first chapter, and you get a little chill, and you know, Oh, this is going to be good? It was like that. Jennifer Doudna, Ph.D. Credit:The New York Times.
Since the beginning of CRISPRs recent discovery as a precise and simple gene editing method, interest in its potential to improve our quality of life has skyrocketed, and with no end in sight. A similar excitement was expressed by one of the co-inventors of CRISPR, Jennifer Doudna from University of California Berkeley.
In 2011, Doudna was approached at a microbiology conference in Puerto Rico by a researcher from Max Planck Institute for Infection Biology, Emmanuelle Charpentier. The two started a conversation that laid the ground work for arguably one of the greatest collaborations, which spurred the invention of CRISPR.
I had this feeling. You know when you pick up a suspense novel, and read the first chapter, and you get a little chill, and you know, Oh, this is going to be good? It was like that, Doudna told The New York Times in 2015.
Surprisingly, the investigation of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) in bacteria is not a new thing. Researchers have been exploring these repeated sequences since the 1980s, but their function was unknown at the time. Then, scientists slowly started to uncover clues about their purpose, which pointed to a built-in adaptive immune system that bacteria used to combat invaders such as viruses.
Within the past few years, researchers like Jennifer Doudna and Emanuelle Charpentier, along with postdoc researcher Martin Jinek, have been tapping into the gene-editing possibilities of the CRISPR-Cas9 system. Meanwhile, Feng Zhang from the Broad Institute and MIT was eager to show that the system worked in mouse and human cells, which he accomplished in his paper published in 2013. He even created an alternative genome engineering method called CRISPR-Cpf1, which may improve the tools precision and power.
Recently, the two groups of researchers entered a fiery battle for a CRISPR patent and the scientific community called for a moratorium on using CRISPR to edit the human germline for fear of unknown repercussions as a result of making heritable changes that could shift the gene pool. It will surely be intriguing to follow the progression of this gene editing system and its uncertain what the future holds.
How it works
The CRISPR-Cas9 system targets precise gene sequences and removes, adds to, or changes them with the help of two components: an enzyme called Cas9 and guide RNA (gRNA). Its based on the naturally occurring ability of bacteria to recognize and destroy invading viruses via a genetic memory.
SEE ALSO: An Epigenetic Link Between Memory Loss and Epilepsy
Cas9 acts as the scissor that snips the DNA and the RNA guide is a tailor-made sequence that ensures Cas9 is cutting in the right place. Researchers are able to program the guide RNA with any sequence of the genetic code they desire in order to lead Cas9 to the proper location.
Other techniques for editing DNA, such as TALENs and zinc finger nucleases were explored by researchers around the same time, but these methods have a much lower level of precision and are significantly more cumbersome. Unlike other techniques, CRISPR can even target multiple genes at once. The beauty of this gene editing system is how relatively simple, accessible, and incredibly precise it is. However, even among the accomplishments there are certainly limitations.
CRISPR accomplishments
As young as the technology is, scientists have been working feverishly with the CRISPR-Cas9 system in several applications. In one study published in PNAS, a group of researchers edited out a gene sequence in mosquitos and replaced it with a DNA segment that rendered them resistant to the parasite that causes malaria, known as Plasmodium falciparum. This could prevent mosquitos from transmitting the disease to humans entirely. Interestingly, when these malaria-resistant genetically modified mosquitos mated, they passed on the resistance to nearly 99% of their offspring. This was true even if a modified mosquito bred with a normal one.
A study conducted by a Chinese research team led by geneticist Lei Qu at Yulin University also demonstrated the successful use of CRISPR to bulk up livestock. They manipulated goats DNA to make them more muscular and produce more wool, in the hopes of bolstering the goat meat and cashmere sweater industry in Shaanxi, China. We believed gene-modified livestock will be commercialized after we demonstrate [that it] is safe, Qu predicted in an article by Scientific American.
Another group of researchers were able to edit out a genetic mutation in mice that causes a disease known as retinitis pigmentosa (RP), which can ultimately lead to blindness. Although not yet approved for use in humans, they were able to restore the mices vision and are hopeful for its therapeutic application in people. They recently published their results in Nature.
Not only can scientists edit genes using CRISPR, but they may be able to change the epigenome using CRISPR as well. Many diseases are not caused by a single genetic mutation but rather disturbed gene expression profiles. Harnessing the ability to edit epigenetic marks could drastically broaden our ability to cure a much wider range of disorders. In theory, perhaps editing our epigenome could allow us to cherry-pick more desirable behaviors.
Researchers can also utilize the power of next generation sequencing to perform chromatin immunoprecipitation sequencing (ChIP-seq) with a CRISPR/Cas9 antibody. The precise, high throughput capability of this method is especially promising because of the target efficiency of the Cas9 enzyme in conjunction with multiple guide RNAs, which can be used simultaneously for multiplexing. Not only can ChIP-seq be useful as an unbiased method for detecting on-target effects of the CRISPR-Cas9 gene editing system, but it might also be used to pinpoint how the system might miss the mark, which would be helpful when developing the system for therapeutic application.
Recently, researchers used the CRISPR-Cas9 system to add acetyl groups to histones, carrying enzymes to certain locations on the genome. Histone modifications, including histone acetylation and histone methylation, have the ability to remodel chromatin to make genes more or less accessible, influencing their expression. Other research suggests we may modify DNA methylation with CRISPR-Cas9, which could prove invaluable for understanding and treating disorders that are linked to this epigenetic modification, such as cancer, lupus, muscular dystrophy, and many others.
Although these studies have been conducted in animal models and the only CRISPR-Cas9 research on non-viable human embryos was performed in China, there is much more to be learned about the effects of CRISPR in humans and how it might be used towards creating what has gained a lot of attention recently superior designer babies.
Continue to the next page to read about designer babies and future directions.
Continued here:
Recommendation and review posted by sam
Gene therapy infection can prevent blindness, research shows – The Independent
A gene therapy that deliberately infects the eye with a virus can safely preserve vision in people affected by one of the leading causes of blindness, research has shown.
In a small preliminary study, scientists used an altered common cold-type virus to carry a repair gene that combats age-related macular degeneration (AMD).
The disease is marked by abnormal blood vessels that leak fluid into the central part of the retina, or macula.
After being injected into patients' eyes, the virus penetrated retinal cells and deposited the gene, which manufactured a therapeutic protein called FLT01.
Lead researcher Professor Peter Campochiaro, from Johns Hopkins University in the US, said: This preliminary study is a small but promising step towards a new approach that will not only reduce doctor visits and the anxiety and discomfort associated with repeated injections in the eye, but may improve long-term outcomes.
The Phase I clinical trial involved 19 men and women aged 50 and older with advanced wet AMD.
With the help of the gene, retinal cells were turned into factories making FLT01.
The scientists hope this will eliminate the need to administer repeated injections of the protein, which suppresses a natural growth-driving molecule called VEGF.
Prolonged suppression of VEGF is needed to preserve vision, and that is difficult to achieve with repeated injections because life often gets in the way, said Prof Campochiaro.
For safety and ethical reasons, the patient group consisted of people for whom standard approved treatments were highly unlikely to restore vision.
Only 11 patients stood any chance of fluid reduction. Of those, four showed dramatic improvements after the gene therapy. The amount of fluid in their eyes dropped from a severe level to almost nothing.
Two other patients experienced a partial reduction in the amount of fluid in their eyes.
The findings are reported in the latest issue of The Lancet medical journal.
Press Association
Follow this link:
Gene therapy infection can prevent blindness, research shows - The Independent
Recommendation and review posted by sam
SENS Research Foundation Announces New Research Program on Somatic Gene Therapy With Buck Institute for … – Markets Insider
MOUNTAIN VIEW, CA--(Marketwired - May 15, 2017) - SENS Research Foundation (SRF) has launched a new research program focused on somatic gene therapy in collaboration with the Buck Institute for Research on Aging. Brian Kennedy, PhD, a leading expert on the biology of aging, will be running the project in his lab at the Buck.
Many potential treatments of age-related diseases require the addition of new genes to the genome of cells in the body, a technology known as somatic gene therapy. The technology has been hampered, up until now, by the inability to control where the gene is inserted. That lack of control resulted in a significant risk of insertion in a location that encourages the cell to become malignant.
SRF has devised a new method for inserting genes into a pre-defined location. In this program, this will be done as a two-step process, in which first CRISPR is used to create a "landing pad" for the gene, and then the gene is inserted using an enzyme that only recognizes the landing pad. SRF has created "maximally modifiable mice" that already have the landing pad, and this project will evaluate how well the insertion step works in different tissues.
"Somatic gene therapy has been a goal of medicine for decades. Being able to add new healthy genes will enable us to address treatments of such age-related diseases as atherosclerosis and macular degeneration. Our collaboration with SRF will substantially move us toward finding effective treatments to genetically based age-related diseases," said Dr. Kennedy.
"Partnering with Brian Kennedy and the Buck enables SRF to continue towards our goal of achieving human clinical trials on rejuvenation biotechnologies in the next five years. Brian's leadership in moving this technology into mammals is a huge step forward," said Dr. Aubrey de Grey, CSO, SENS Research Foundation.
This research has been made possible through the generous support of the Forever Healthy Foundation and its founder Michael Greve, as well as the support of our other donors. The Forever Healthy Foundation is a private nonprofit initiative whose mission is to enable people to vastly extend their healthy lifespans and be part of the first generation to cure aging. In order to accelerate the development of therapies to bring aging under full medical control, the Forever Healthy Foundation directly supports cutting-edge research aimed at the molecular and cellular repair of damage caused by the aging process.
About SENS Research Foundation (SRF)SENS Research Foundation is a 501(c)(3) nonprofit that works to research, develop, and promote comprehensive regenerative medicine solutions for the diseases of aging. SRF is focused on a damage repair paradigm for treating the diseases of aging, which it advances through scientific research, advocacy, and education. SENS Research Foundation supports research projects at universities and institutes around the world with the goal of curing such age-related diseases as macular degeneration, heart disease, cancer, and Alzheimer's disease. Educating the public and training researchers to support a growing regenerative medicine field are also major endeavors of the organization that are being accomplished though advocacy campaigns and educational programs. For more information, visit http://www.sens.org.
About Buck Institute for Research on AgingBuck Institute is the U.S.'s first independent research organization devoted to Geroscience -- focused on the connection between normal aging and chronic disease. Based in Novato, California, the Buck is dedicated to extending "healthspan," the healthy years of human life, and does so by utilizing a unique interdisciplinary approach involving laboratories studying the mechanisms of aging and others focused on specific diseases. Buck scientists strive to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer's and Parkinson's, cancer, cardiovascular disease, macular degeneration, osteoporosis, diabetes and stroke. In their collaborative research, they are supported by the most recent developments in genomics, proteomics, bioinformatics and stem cell technologies. For more information: http://www.thebuck.org.
See the original post:
SENS Research Foundation Announces New Research Program on Somatic Gene Therapy With Buck Institute for ... - Markets Insider
Recommendation and review posted by sam
Sangamo Receives Fast Track Designation From The FDA For SB-525 Investigational Hemophilia A Gene Therapy – PR Newswire (press release)
SB-525 has already received Orphan Drug designation from the FDA. The FDA has cleared an Investigational New Drug application for this program, and a Phase 1/2 clinical trial evaluating SB-525 in adults with hemophilia A is expected to open and begin screening subjects for enrollment by the end of the second quarter 2017. Data from this study are expected in late 2017 or early 2018.
About Hemophilia A
Hemophilia A is a monogenic, rare bleeding disorder in which the blood does not clot normally. It is caused by mutations in the F8 gene which encodes Factor VIII clotting protein that helps the blood clot and stop bleeding when blood vessels are injured. Individuals with this mutation experience bleeding episodes after injuries and spontaneous bleeding episodes that often lead to joint disease such as arthritis. According to the Centers for Disease Control and Prevention, hemophilia occurs in about one of every 5,000 male births, with an estimated 20,000 males in the U.S. living with the disorder.
About Sangamo Therapeutics
Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic therapies that transform patients' lives using the company's industry leading platform technologies in genome editing, gene therapy, gene regulation and cell therapy. The Company is advancing Phase 1/2 clinical programs in Hemophilia A and Hemophilia B, and lysosomal storage disorders MPS I and MPS II. Sangamo has an exclusive, global collaboration and license agreement with Pfizer Inc. for gene therapy programs for Hemophilia A, with Bioverativ Inc. for hemoglobinopathies, including beta thalassemia and sickle cell disease, and with Shire International GmbH to develop therapeutics for Huntington's disease. In addition, it has established strategic partnerships with companies in non-therapeutic applications of its technology, including Sigma-Aldrich Corporation and Dow AgroSciences. For more information about Sangamo, visit the Company's website at http://www.sangamo.com.
Forward Looking Statements
Thispressreleasemaycontainforward-looking statements based on Sangamo's current expectations. Theseforward-looking statements include, without limitation references relating to the benefit of Fast Track designation to accelerate regulatory approval of SB-525, research and development of therapeutic applications of Sangamo's gene therapy and ZFP technology platforms, the potential of Sangamo's technology to treat hemophilia and lysosomal storage disorders, and the expected timing of initiating clinical trials of SB-525 and the release of data from these trials. Actual results may differ materially from these forward-looking statements due to a number of factors, includinguncertaintiesrelatingto substantial dependence on the clinical success of lead therapeutic programs,the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's SEC filings, including the risk factors described in its Annual Report onForm10-K and its most recent QuarterlyReportonForm10-Q. Sangamo Therapeutics, Inc. assumes no obligation to update the forward-looking information contained in this pressrelease.
To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/sangamo-receives-fast-track-designation-from-the-fda-for-sb-525-investigational-hemophilia-a-gene-therapy-300458224.html
SOURCE Sangamo Therapeutics, Inc.
Read this article:
Sangamo Receives Fast Track Designation From The FDA For SB-525 Investigational Hemophilia A Gene Therapy - PR Newswire (press release)
Recommendation and review posted by simmons
Sangamo Biosciences (SGMO) Presents Recent Developments from Research and Clinical Programs at ASGCT – StreetInsider.com
Find out which companies are about to raise their dividend well before the news hits the Street with StreetInsider.com's Dividend Insider Elite. Sign-up for a FREE trial here.
Sangamo Therapeutics, Inc. (NASDAQ: SGMO) today highlighted data from research and clinical-stage programs presented over the past week at the 20th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT). Research from Sangamo scientists and collaborators was selected for 10 oral presentations and nine poster presentations during the conference.
"This year at ASGCT we showcased several exciting research and clinical programs emerging from Sangamo's laboratories," said Dr. Sandy Macrae, Sangamo's CEO. "Sangamo is known for its leading research in genome editing, and over time we have developed additional expertise in gene therapy, gene regulation and cell therapy. We are also rapidly advancing our viral and non-viral delivery capabilities which have the potential to broaden our applications of genomic therapies. Such range of expertise allows us to be selective as we pair technology platforms with therapeutic applications, and compels us to make strategic choices about our product candidates. We will develop and commercialize certain products ourselves, while others, such as our gene therapy for hemophilia A now in collaboration with Pfizer, or our CNS or oncology programs, we may advance with a partner to leverage the right disease area focus, skills and resources."
Selected Highlights from ASGCT 2017
Zinc Finger Nuclease Technology ImprovementsEd Rebar, Ph.D., Sangamo's vice president of technology, presented recent enhancements to the Company's zinc finger nuclease (ZFN) genome editing technology that substantially improve specificity while maintaining very high levels of on-target modification. These include the removal of positively charged amino acids in the zinc finger beta-sheet that make non-specific contacts with the DNA phosphate backbone, as well as the substitution of key residues within the Fok-1 cleavage domain. Dr. Rebar showed that these refinements could be applied broadly to ZFN reagents to substantially reduce off-target cleavage without sacrificing on-target cutting efficiency.
Dr. Rebar concluded with a detailed specificity analysis of a ZFN pair, in which these approaches were combined, which identified no significant off-target modification with an assay sensitivity of approximately 0.1%. Importantly, this study was performed on samples generated using clinically relevant delivery conditions, transfection scales and cell types, and with an on-target modification level of greater than 80%.
Gene Therapy for Fabry DiseaseThomas Wechsler, Ph.D., Sangamo's director and lead scientist for rare diseases, presented new data from the Company's preclinical AAV-cDNA gene therapy program for Fabry disease. Earlier in the week, Sangamo announced that it will advance this program toward human clinical development with preclinical studies enabling an Investigational New Drug Application (IND) in the second half 2018.
Fabry is an X-linked lysosomal storage disorder caused by mutations in the GLA gene that encodes for the alpha-galactosidase A enzyme (-Gal A). This mutation results in the buildup of Gb3 and Lyso-Gb3 lipid molecules in the body's cells, resulting in a range of symptoms and life-threatening complications that affect multiple tissues and organ systems in the body.
Dr. Weschler presented data from GLAKO mouse models of Fabry disease demonstrating that a single infusion of Sangamo's AAV vector containing an -Gal A transgene and a liver specific promoter successfully transduced the liver, resulting in episomal expression of -Gal A in the plasma and various tissues for the duration of the study, out to 60 days. From a single treatment, the AAV-cDNA vector achieved enzyme activity levels in the plasma of up to 100 fold greater than wildtype and 10 to 100 fold greater than wildtype in tissues including the liver, heart, kidney and spleen. Importantly, -Gal A secreted from the liver led to a significant reduction in the levels of accumulated Gb3 and Lyso-Gb3 lipid substrates, in target tissues such as the kidney and heart.
Gene Regulation Treatment for Reduction of TauSangamo Scientist Bryan Zeitler, Ph.D., presented recent data demonstrating significant reduction of tau expression using Sangamo's proprietary zinc finger protein transcription factor (ZFP-TF) gene-regulation technology. The research was conducted in conjunction with Dr. Brad Hyman, Director of the Alzheimer's Disease Research Center at Massachusetts General Hospital. The reduction of tau expression has been shown to help reduce neurofibrillary tangles in the brain and provide neuronal protection and reversal of pathology in Alzheimer's disease and other tauopathy disease models.
The presentation included data from in vivo studies in wild-type mice demonstrating up to 90% reduction of tau mRNA and protein in the mouse hippocampus, as well as up to 70% tau reduction across all regions of the brain, including the cortex, midbrain, cerebellum, thalamus, hypothalamus and striatum.
In addition, data from in vivo studies in an amyloid mouse model of Alzheimer's disease suggest that a single administration of ZFP-TFs significantly reduced neuronal dystrophies in mice with established disease pathology. This is the first time that a tau lowering agent has demonstrated a reduction in neuritic dystrophy. Specificity and off-target analysis in ZFP-TF-treated primary neurons revealed that tau was the only gene suppressed out of more than 26,000 coding transcripts analyzed. New data in Dr. Zeitler's presentation demonstrated that the effect of ZFP-TF treatment in lowering tau was durable out to the last measurement, at 11 months.
These experiments were conducted using Sangamo's novel, proprietary AAV serotype for improved CNS transduction.
Sangamo intends to seek a partner with disease area expertise for the development and commercialization of its gene regulation approach for certain central nervous system applications including Alzheimer's disease and other tauopathies.
In Vivo Genome Editing Treatments for MPS I and MPS IISangamo Scientist Russell DeKelver, Ph.D., presented additional preclinical data from the Company's in vivo genome editing clinical programs in MPS I and MPS II demonstrating phenotypic correction of disease in mouse models following a single administration of Sangamo's genome editing treatments. Newly presented histopathological analysis demonstrated reduced cellular vacuolation in various secondary tissues, as well as in the bone marrow, and central nervous system tissues such as the spinal cord and pituitary gland in treated MPS I and MPS II mice, four months after dosing. Furthermore, newly presented mass spectrometry analysis confirmed significant reduction of dermatan sulfate, a type of GAG biomarker, in the brains of MPS I and MPS II mice treated with Sangamo's genome editing treatments.
Sangamo recently initiated two Phase 1/2 clinical trials evaluating SB-318 and SB-913, ZFN-mediated in vivo genome editing treatments for MPS I and MPS II, respectively. Data are expected in late 2017 or early 2018.
Cell TherapyResearch by Brigit Riley, Ph.D., Sangamo's director of discovery and translational research, was presented demonstrating high levels of homology driven genome editing of human B cells by ZFN mRNA and AAV6 transgene delivery. The data demonstrated robust ZFN-mediated, site-specific modification of B cells at targeted loci, including AAVS1, CCR5 and TRAC locus. The data also demonstrated high levels of targeted transgene insertion, driven by homology directed repair, using a B cell specific promoter. Analysis of AAV serotype transduction showed the superiority of AAV6 in transducing B cells compared to several other serotypes.
The data demonstrate the potential for using genome editing to genetically modify B cells ex vivo and harness their natural ability to produce large amounts of antibodies to generate protein production reservoirs. This novel approach for using genome editing to harness the protein production capacity of B cells could be relevant for multiple indications, including immune disorders, cancer immunotherapies and other monogenic disorders.
DeliverySangamo Scientist Anthony Conway, Ph.D., presented new data from the Company's research into a next-generation delivery platform using lipid nanoparticles (LNPs). ZFN mRNA delivery via LNPs allowed for accumulation of genome modification within the mouse liver following repeat administration, with progressive increases in genomic modification out to six repeat doses tested. LNP delivery of new ZFN architectures led to greater than 85% on-target modification in vitro and greater than 60% on-target modification in vivo, resulting in greater than 90% protein knockdown of TTR and PCSK9 in wildtype mice. Repeat dosing of ZFNs using LNP-mRNA in combination with a single human AAV-IDS donor vector resulted in efficient targeted insertion of the IDS gene into the albumin locus and accumulative enzymatic activity levels in mouse plasma after each subsequent dose.
Recommendation and review posted by sam
Stem cell transplants may advance ALS treatment by repair of blood-spinal cord barrier – Science Daily
Researchers at the University of South Florida show in a new study that bone marrow stem cell transplants helped improve motor functions and nervous system conditions in mice with the disease Amyotrophic Lateral Sclerosis (ALS) by repairing damage to the blood-spinal cord barrier.
In a study recently published in the journal Scientific Reports, researchers in USF's Center of Excellence for Aging and Brain Repair say the results of their experiment are an early step in pursuing stem cells for potential repair of the blood-spinal cord barrier, which has been identified as key in the development of ALS. USF Health Professor Svitlana Garbuzova-Davis, PhD, led the project.
Previous studies in development of various therapeutic approaches for ALS typically used pre-symptomatic mice.
"This is the first study advancing barrier repair that treats symptomatic mice, which more closely mirrors conditions for human patients," Dr. Garbuzova-Davis said.
Using stem cells harvested from human bone marrow, researchers transplanted cells into mice modeling ALS and already showing disease symptoms. The transplanted stem cells differentiated and attached to vascular walls of many capillaries, beginning the process of blood-spinal cord barrier repair.
The stem cell treatment delayed the progression of the disease and led to improved motor function in the mice, as well as increased motor neuron cell survival, the study reported.
ALS is a progressive neurodegenerative disease that affects neuronal cells in the brain and the spinal cord, which send signals to control muscles throughout the body. The progressive degeneration of motor neuron cells leads to death from ALS. More than 6,000 Americans each year are diagnosed with the disease.
Because stem cells have the ability to develop into many different cell types in the body, researchers at USF's Center of Excellence for Aging and Brain Repair, Department of Neurosurgery & Brain Repair have focused on using stem cells to restore function lost through neurodegenerative disorders or injuries.
Damage to the barrier between the blood circulatory system and the central nervous system has been recently recognized as a factor in ALS development, leading researchers to work on targeting the barrier for repair as a potential strategy for ALS therapy.
In this study, the ALS mice were given intravenous treatments of one of three different doses of the bone marrow stem cells. Four weeks after treatment, the scientists determined improved motor function and enhanced motor neuron survival. The mice receiving the higher doses of stem cells fared better in the study, the researcher noted.
The transplanted stem cells had differentiated into endothelial cells -- which form the inner lining of a blood vessel, providing a barrier between blood and spinal cord tissue -- and attached to capillaries in the spinal cord. Furthermore, the researchers observed reductions in activated glial cells, which contribute to inflammatory processes in ALS.
Story Source:
Materials provided by University of South Florida (USF Health). Note: Content may be edited for style and length.
Recommendation and review posted by sam
Carson Tahoe Health opens blood and bone marrow transplant care clinic – Nevada Appeal
On Tuesday, Carson Tahoe Cancer Center opened a new blood and bone marrow transplant care clinic with support from the Huntsman Cancer Institute (HCI) at the University of Utah. Under the collaboration, a Bone Marrow Transplant (BMT) physician and nurse from HCI will travel to Carson City once a month to treat patients both before and after they receive a transplant.
Blood and marrow transplants are performed in patients with cancers of the blood and lymphatic systems, including leukemia, lymphoma and multiple myeloma. The transplants replace bone marrow that has been damaged or destroyed with a supply of healthy blood stem cells, which in turn travel to the bone marrow and promote growth of new marrow.
Currently, patients in the Northern Nevada area who need a transplant must travel outside the area for treatment. Through this model, patients will still receive their transplant at HCI in Salt Lake City. But they will now be able to receive care at the Carson Tahoe clinic for planning and follow-up appointments, which typically occur every month for a year following transplant.
"This clinic is going to enable patients to receive more of their pre-and post-BMT care closer to home," said Daniel Couriel, MD, Professor of Medicine at the University of Utah and Director of HCI's BMT program. "We hope to maximize the time patients can spend in their own homes with their loved ones as they recover."
The BMT clinic will be open the third Monday of every month. Patients can access the clinic by referral.
"Because of the added bench strength we receive from HCI, we are better equipped to provide outstanding bone marrow transplant care, close to home," said Ed Epperson, CEO of CTH.
CTH formally affiliated with University of Utah Health in 2013 and with Huntsman Cancer Institute in 2015 in an effort to improve accessibility to specialty care for Northern Nevada residents. The relationship between the health care systems provides resources that allow Carson Tahoe Health to meet the ever-changing health care needs of the community.
"Both organizations share a commitment to providing the highest quality cancer care to patients, no matter where they live," said John Sweetenham, MD, Executive Medical Director at Huntsman Cancer Institute and Professor of Medicine at the University of Utah. "BMT treatment is a very unique type of care, and we look forward to working with Carson Tahoe to bring this service to the community."
To find out more about the clinic, residents can call Carson Tahoe Cancer Center at 775-445-7500.
More here:
Carson Tahoe Health opens blood and bone marrow transplant care clinic - Nevada Appeal
Recommendation and review posted by sam
Cord Blood: A Small Amount Does A Lot Of Good | KERA News – KERA News
An umbilical cord after birth yields about three to five ounces of cell-rich cord blood. That's not a lot, but enough of it can help treat more than 80 or so diseases. A North Texas oncologist says education's key to boosting limited supply.
The KERA Interview with Dr. Sharif
Dr. Suhail Sharif is a surgical oncologist with Texas Health Fort Worth.
Interview Highlights:
Whats special about cord blood: Cord blood has immature blood cells, and you can use these stem cells to, basically, harvest into these patients that have problems with their own blood; for example, because of leukemia or lymphoma or other types of diseases that affect their own blood lines. These can grow into the red blood cells if [they're] deficient or the white blood cells if [they're] deficient or even platelets, for that matter.
Cord blood cells vs. bone marrow cells: Cord blood stem cells are actually stored in a blood bank that you can use on patients that need it. But bone marrow, you actually have to go through a process of harvesting the bone marrow. Its a very painful procedure for whoever is donating the bone marrow. And then they have to go through an extensive and rigorous testing, not only for infectious causes, but also to see if they match with the patient. And then they have to harvest, and they basically have to transplant it. Now, that whole process can take a few months. If you just have cord blood stem cells, these have already been stored and are readily available. And if you have a match with the donor and the recipient, you can use them right away.
Cord blood is limited in supply: If you think about the blood that is in the placenta and the cord, its in the range of three to five ounces. Thats about like half a cup. Thats the reason why you have to gather it from a lot of patients. At this point, there are, I believe, close to 175,000 matched cord blood available."
But its not enough: If you think about what percentage of deliveries actually translate into donating cord blood, its very miniscule. Thats why were educating the parents about the benefits of cord blood so they can donate to a public blood bank so that we can use it in treating patients with deadly cancers and so forth in our community.
For more information:
See the article here:
Cord Blood: A Small Amount Does A Lot Of Good | KERA News - KERA News
Recommendation and review posted by simmons
Lotusland 17: BC’s diverse population needs diverse stem cell donors – Delta-Optimist
This month is the annual ExplorAsian festival, which celebrates Asian heritage in Metro Vancouver. It features a large number of events from lectures to arts and entertainment.
One of the events held Saturday, May 13, at Metrotown in Burnaby is a little bit different. Held in partnership with Canadian Blood Services, its an outreach to the Asian community and those from multi-ethnic or biracial backgrounds to consider becoming a stem cell donor. Matching blood types is relatively easy matching stem cell and bone marrow donors to patients in need is quite hard, especially for those from diverse backgrounds. In fact the more diverse we become in B.C., the more critical our need for diverse donors.
I talked to the organizers of the Thanks Mom Give Life 2017 campaign this week.
You can find out more information about stem cell and blood donation at Canadian Blood Services.
For more information on craft beer, you can find The Growler here.
Want new episodes delivered to you automatically and easily? Subscribe to This is Lotusland through iTunes, Tunein and Stitcher or use our RSS feed.
RSS
http://feeds.soundcloud.com/users/soundcloud:users:183580457/sounds.rss
iTunes
https://itunes.apple.com/ca/podcast/this-is-lotusland/id1063810628
Stitcher
http://app.stitcher.com/browse/feed/78857/details
Tunein
Read the original post:
Lotusland 17: BC's diverse population needs diverse stem cell donors - Delta-Optimist
Recommendation and review posted by Bethany Smith
Skin regeneration, universal donor stem cells and new SMA treatment approach – The San Diego Union-Tribune
Injured skin repairs itself with the help of stem cells, but how this process works isnt well understood. A new study proposes that differentiated skin cells turn back into stem cells to heal the wound.
The process is regulated by a protein called Gata6 made by sebaceous duct cells. In response to injury, these cells migrate out into the skin and de-differentiate into stem cells, which then give rise to replacement skin, according to researchers led by Fiona Watt of Kings College London.
The study was published in Nature Cell Biology. When placed online, the study, Wounding induces dedifferentiation of epidermal Gata6 cells and acquisition of stem cell properties, can be found at j.mp/skincells. Watt was senior author. Giacomo Donati, also of Kings College London, was senior author.
Our data not only demonstrate that the structural and functional complexity of the junctional zone is regulated by Gata6, but also reveal that dedifferentiation is a previously unrecognized property of post-mitotic, terminally differentiated cells that have lost contact with the basement membrane, the study stated.
This resolves the long-standing debate about the contribution of terminally differentiated cells to epidermal wound repair.
One of the most-anticipated results of stem cell research would be generation of replacement tissues for those lost by disease or injury. But the potential for immune rejection limits this potential. While immune-matching can be achieved through patient-derived induced pluripotent stem cells, this process takes time and is costly.
Immune-tolerant allogenic stem cells have been produced in a study reported Monday in Nature Biotechnology. These cells were produced by making them express minimally variant human leukocyte antigen class E molecules. Production of these molecules causes a self response that inhibits attack by NK natural killer cells.
When published, the study, HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells, can be found online at j.mp/allogenic. David W Russell was senior author and Germn Gornalusse was first author. Both are of University of Washington, Seattle.
A study conducted in a mouse model of spinal muscular atrophy suggests that symptoms might be reduced by increasing the activity of synapses between sensory and motor neurons. It suggests there may be more than one path to improving or preserving muscle function in SMA patients.
SMA is caused by the deterioration and eventual death of spinal motor neurons. The only treatment shown to affect the underlying course of the disease, Spinraza, was researched by Ionis Pharmaceuticals in Carlsbad and brought to market in a partnership with Biogen.
The study was published Monday in Nature Neuroscience. George Z Mentis was the senior author and Emily V Fletcher was first author. Both are of Columbia University in New York. When placed online, the study, Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy, can be found at j.mp/smanew.
Researchers treated the mice with kainate, which restored near-normal synaptic functioning and improved motor functioning. While the chemical induces seizures, the mice were given doses lower than the seizure threshold.
Because of kainates seizure-inducing potential, the researchers are looking for safer chemicals to stimulate the synaptic connections.
bradley.fikes@sduniontribune.com
(619) 293-1020
Read the original post:
Skin regeneration, universal donor stem cells and new SMA treatment approach - The San Diego Union-Tribune
Recommendation and review posted by sam