Daily Archives: September 20, 2022

Ring Therapeutics

CAMBRIDGE, Mass., Sept. 20, 2022 (GLOBE NEWSWIRE) -- Ring Therapeutics, a life sciences company founded by Flagship Pioneering to revolutionize gene therapy with its commensal virome platform, today announced the issuance of U.S. Patent No. 11,446,344. The patent, which was granted to Flagship Pioneering, is exclusively licensed to Ring Therapeutics.

The patent covers anellovirus vectors, which can be used to deliver a diversity of therapeutic modalities. This patent builds on a previous patent (U.S. Pat. No. 11,166,996) granted in November 2021 on methods of delivering a therapeutic polypeptide or nucleic acid by administering Anellovector compositions.

"Ring has comprehensively pioneered a new class of viral vector by generating scientific understanding of anelloviruses through our research work and publications, said Tuyen Ong, MD, MBA, Chief Executive Officer of Ring Therapeutics. This patent issuance supports the novelty of the Anellogy platform and our unique approach of harnessing the human commensal virome to engineer life-saving therapies, ultimately redefining what is possible in programable medicine.

Avak Kahvejian, Ph.D., General Partner of Flagship Pioneering and Co-Founder and Chairman of Ring added, This is another example of Flagship Pioneering companies conducting science at the frontiers of human biology to develop new solutions for humanity. Rings conception of Anellovectors as a broad bioplatform that could be applicable across diseases holds tremendous promise for unlocking the field of genetic medicines.

About Ring Therapeutics

Ring Therapeutics is revolutionizing the gene therapy and nucleic acid medicine space by harnessing the most abundant and diverse member of the human commensal virome, anelloviruses. The company developed the Anellogy platform which focuses on anelloviruses to potentially treat a broad range of diseases. Through harnessing the unique properties of these commensal viruses, the Anellogy platform generates diverse vectors that exhibit both tissue-specific tropism and the potential to be redosed. Founded by Flagship Pioneering in 2017, Ring Therapeutics aims to develop and further expand its portfolio through leveraging its platform to unlock the full potential of gene therapy and nucleic acid medicines, enabling a variety of mechanisms that successfully deliver therapeutic cargo to unreachable organs and tissues. To learn more, visithttps://ringtx.com or follow us on Twitter at@Ring_tx.

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Ring Therapeutics Media:Brittany Leigh, Ph.D.LifeSci Communicationsbleigh@lifescicomms.com+1-813-767-7801

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Ring Therapeutics Announces Issuance of U.S. Patent for its Anellovector Compositions - Yahoo Finance

An unexplained case of severe coronary artery disease in a seemingly healthy young man led scientists at The Ohio State University Wexner Medical Center and College of Medicine to a discovery that could lead to a new way to treat high cholesterol.

Ohio State scientists discovered rare genetic mutations that had never been identified before, and that could cause severe early onset of coronary artery disease, the most common type of heart disease in the United States. The discovery is leading to a better understanding of how cholesterol functions and the possibility of developing safer therapeutics for the 94 million Americans with high cholesterol.

Marcus Wright, of Delaware, Ohio, was 27 when he suffered a heart attack and continued to have heart-related problems. Doctors were puzzled after finding out he had severe coronary artery disease despite being active and eating a healthy diet.

He was eventually referred to Dr. Ernest Mazzaferri, Jr., an interventional cardiologist at Ohio States Richard M. Ross Heart Hospital and a clinical professor of Internal Medicine.

When I met Marcus about 14 years ago, he looked like a linebacker for the Ohio State Buckeyes. He was super fit and active. He was the last guy that you would ever think would have this kind of disease, said Mazzaferri, co-interim director of Ohio States Heart and Vascular Center. His cholesterol and inflammation numbers looked pretty good and there was no family history of heart disease at that point, so it didn't make sense why somebody like him would have such advanced disease.

Despite optimal medical therapy, Wright continued to have symptoms and needed multiple heart stents, which are expandable metal coils placed in a blocked blood vessel to keep the arteries open.

When both Wrights mother and younger brother were later diagnosed with severe coronary artery disease, Mazzaferri suspected there was a genetic link. He decided it would be a good case for Ohio States JB Project, which is funded by philanthropy and brings together clinicians and scientists to decipher the root cause of highly unusual cases involving coronary artery disease, arrhythmias and heart failure.

Marcus became the first patient I ever presented to our genetic scientists and I said, 'Nobody can figure out what's wrong with this young man. I need your help to understand what's wrong with him,'" said Mazzaferri, who holds the Charles A. Bush, MD Professorship in Cardiovascular Surgery.

A team of researchers led by Sara Koenig, assistant professor of Internal Medicine, conducted genetic sequencing of Wrights DNA and identified unique genetic variants that were causing his advanced disease. To better understand the potential implications of these genetic mutations, Koenig expanded her study, identifying the same mutations in his mother, father and brothers.

This gene encodes a receptor for HDL, which is classically referred to as your good cholesterol, Koenig said. We hypothesize that good cholesterol does not function as well in these individuals as the general population.

The researchers determined that Wrights genetic variants prevented his good cholesterol from effectively clearing out his bad cholesterol (known as LDL), leading to his advanced coronary artery disease. Their findings were published in the American Heart Associations Circulation Research.

The identification of these specific variants in Marcus and his family and knowing that they are causing coronary artery disease sheds lights on a new pathway that we can approach for cholesterol mediated therapy, Koenig said.

Researchers examined 788 FDA drugs approved for various diseases to narrow down which ones may promote a healthy HDL function. They are now working on developing different diagnostic tests and a new therapeutic drug that may provide an alternative option for those living with high cholesterol.

Genetics play a really important role in cholesterol and cardiovascular disease. Even if youre doing everything right by exercising and eating the right foods, some people are just predisposed to high cholesterol and coronary artery disease, which is exactly what happened to Marcus, Koenig said. The issue with statins, which lower your cholesterol, is that theyre not 100% effective. Weve identified a handful of drugs that promote the good HDL pathway or reverse cholesterol transport. Now we are investigating these drugs in animal and human cell models in the hope that we can identify how they affect the pathway and develop more targeted therapies.

Over the years, Mazzaferri has made changes to Wrights medications and now only sees him once a year.

We do the things we do with the hope that we're going to be able to impact people's lives, and to have a group like the JB project work together over a couple year period to really solve a problem like this was one of the most memorable things I'll ever have in my career, Mazzaferri said.

Knowing what was causing his heart problems and learning he probably didnt pass the genetic mutations along to his three children was a relief for Wright.

It was a relief because you're like Okay, now somebody knows something instead of just being a medical mystery, Wright said. They're saying the likelihood is I wouldn't pass it on. As a father, that's the biggest thing that you could be concerned with. I know my parents didn't want to give it to me, and this shouldnt be one of those things that my kids have to worry about.

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Cholesterol gene mutation: Why would a healthy 27-year-old have severe heart problems? - 69News WFMZ-TV

An analysis found that a single dose of gene therapy would be more cost-effective than on-demand or prophylaxis factor replacement in 92% of cases.

Hemophilia is a hereditary, lifelong, and life-threatening disorder that, until recently, has had no prospective cure. Gene therapy might change that, but the cost has been predicted to be in the millions.

Individuals with hemophilia have a gene mutation that causes a deficiency in one of two factors integral in the blood coagulation pathway. In hemophilia A, factor XIII is missing; in hemophilia B, its factor IX. Hallmark symptoms of the disease include excessive bleeding after internal or external trauma. Areas particularly affected are joints, muscles, and soft tissues. In severe cases, bleeding can occur spontaneously.

Current therapy for hemophilia consists of on-demand or prophylactic intravenous infusions of replacement clotting factor to treat or prevent bleeding. Prophylaxis therapy requires several infusions per week, and the cost can range from $300,000 to $776,000 per year.

Recent research on gene therapy introduces the possibility to significantly reduce or eliminate the need for factor replacement therapy. Treatment is designed as a one-time intravenous injection consisting of an adeno-associated virus vector carrying instructions for liver cells to produce deficient coagulation factors.

At least three gene therapies for hemophilia B are currently in late-stage clinical trials, and all have demonstrated at least a 90% reduction in bleeding events and the need for factor replacement. If all goes well, gene therapy can be a potential cure for hemophilia, but the cost has been estimated at $2 to $3 million per patient.

St. Jude Childrens Research Hospital conducted a cost-effectiveness analysis of gene therapy for severe hemophilia B and found that the novel treatment may be more cost-effective than current therapy despite its sky-high price tag. In the analysis, published in the journal Blood last November, St. Jude used its own hospitals data to compare the cost and cost effectiveness of gene therapy with on-demand and prophylaxis factor replacement therapy.

Researchers calculated a total per-patient cost of $87,198 for the manufacturing, distribution, and five-year follow-up of gene therapy for severe hemophilia B. Taking into account the cost of lifelong factor replacement therapy, bleeding complications during on-demand treatments, orthopedic surgery, and hospitalizations, the analysis found that a single dose of gene therapy would be more cost-effective than on-demand or prophylaxis factor replacement in 92% of cases.

According to the authors, gene therapy is in a unique position when it comes to cost analysis. Nancy Bolous, M.D., from St. Jude Global Pediatric Medicine and lead author of the analysis, said, Gene therapy is different because unlike other treatment approaches, it is a long-lasting, one-time treatment and may require a big upfront payment, a payment that can make the affordability seem questionable. Our analysis importance is that it sheds light on the many factors that could play a role in the decision-making process regarding reimbursement.

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Gene Therapy for Severe Hemophilia B Could Be More Cost Effective Than Current Treatments - Managed Healthcare Executive

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company working to free people from a lifetime of genetic disease, today announced that the U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation to AVR-RD-04, an investigational gene therapy for the treatment of cystinosis, a life-threatening disease that causes progressive multi-organ damage, including early, acute kidney disease progressing to end-stage kidney disease.

FDAs Rare Pediatric Disease Designation and Voucher Program is intended to facilitate the development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. Companies that receive approval for a New Drug Application (NDA) or Biologics License Application (BLA) for a rare pediatric disease may be eligible to receive a voucher for a priority review of a subsequent marketing application for a different product. The priority review voucher may be used by the company or sold to a third party.

AVR-RD-04 is designed to genetically modify patients own hematopoietic stem cells (HSCs) to express the gene encoding cystinosin, the protein that is critically deficient in people living with cystinosis.

Preliminary data from the ongoing University of California San Diego Phase 1/2 clinical trial suggest that this approach is well tolerated, with no adverse events (AEs) related to the drug product reported to date. All AEs reported were related to myeloablative conditioning, stem cell mobilization, underlying disease or pre-existing conditions. The majority of AEs were mild or moderate and resolved without clinical sequelae. Clinical data to date indicate this investigational approach provides benefits in multiple tissues evaluated, including the eyes, skin, gastrointestinal mucosa and the neurocognitive system. The collaborator-sponsored Phase 1/2 clinical trial is funded in part by grants to University of California San Diego from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH).

About CystinosisCystinosis is a rare, progressive disease that impacts approximately 1,600 patients in the U.S., Europe and Japan and is marked by the accumulation of cystine in cellular organelles known as lysosomes. Untreated cystinosis is fatal at an early age. The current SOC for cystinosis, a treatment regimen that can require dozens of pills per day, does not prevent overall disease progression and carries side effects, such as breath and body odor and gastrointestinal symptoms, which can impede compliance. More than 90% of treated cystinosis patients require a kidney transplant in the second or third decade of life.

About AVROBIOOur vision is to bring personalized gene therapy to the world. We target the root cause of genetic disease by introducing a functional copy of the affected gene into patients own hematopoietic stem cells (HSCs), with the goal to durably express the therapeutic protein throughout the body, including the central nervous system. Our first-in-class pipeline includes clinical programs for cystinosis and Gaucher disease type 1, as well as preclinical programs for Gaucher disease type 3, Hunter syndrome and Pompe disease. Our proprietary plato gene therapy platform is designed to be scaled to support late-stage clinical development and commercialization globally. We are headquartered in Cambridge, Mass. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking StatementsThis press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our preclinical and clinical product candidates, including AVR-RD-04 for the treatment of cystinosis, the potential benefits and incentives provided by FDAs rare pediatric disease designation for AVR-RD-04, the design, commencement, enrollment and timing of planned clinical trials, preclinical or clinical trial results, product approvals and regulatory pathways, our plans and expectations with respect to interactions with regulatory agencies, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, and the expected safety profile of our preclinical and investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, including beneficial effects seen in multiple organs and tissues, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

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AVROBIO Receives Rare Pediatric Disease Designation from U.S. Food and Drug Administration (FDA) for First Gene Therapy in Development for Cystinosis...

The relatively short history of cell and gene therapy is not lacking in dramatic moments. A previous outlier, this vibrant field now represents the next great hope and so, when roadblocks to progress are removed or even lowered, theres reason to celebrate. Here, seven members of The Medicine Maker Power List 2022, reflect on the most impactful cell and gene milestones.

There have been many significant breakthroughs in cell and gene therapy over the past few years. Specifically in gene-modified cell therapy, the CAR T story is remarkable. Over the past several years, multiple autologous CAR T therapies have been successfully translated from bench to bedside and received marketing authorization as potentially curative therapies for patients with recalcitrant cancer indications: Kymriah and Yescarta for treating r/r/ ALL, MCL, and LBCL, and Abecma for treating r/r multiple myeloma.

Equally impressive in gene therapy, Zolgensma, an AAVSMN1 gene replacement product, has been developed for use as a one-time gene replacement treatment for infants with spinal muscular atrophy (SMA). The 15 year follow-up study these tiny patients are enrolled in after treatment will inform us on the long-term safety and efficacy of gene replacement therapy.

These products have been translated by academia and SMEs and partnered for advanced development with pharma to achieve both medical and commercial success.

The biggest breakthrough is our increasing ability to edit genes with a growing number of new classes of gene editing tools. This advance has led to the boom of CAR T products and is opening the path to cell engineering and in vivo gene therapy.

In parallel, we are seeing an evolution from viral delivery to alternatives with growing payload capacity. This will, as we are already seeing, lead to cures in diseases where that was unthinkable before!

Cell and gene therapies are at the forefront of innovation and transforming how we treat and potentially cure certain diseases. Cell and gene therapies(CGTs) have the potential to treat severe diseases, such as cancer, as well as rare diseases. Several such therapies are now on the market, including a treatment for an inherited retinal disease that causes blindness. That particular CGT represents an important medical milestone because it was the first curative gene therapy approved for use. Personally, I was excited and humbled at the same time to have been the Global Head bringing this transformational therapy to patients around the world. Many other CGTs are now in development and hopefully will lead to an expansion of the still-limited treatment options available to many patients and transform the clinical paradigm.

An important breakthrough? The demonstration that gain-of-function genetically weaponized somatic cells are potent pharmaceuticals in their own right: living synthetic therapeutics (LSTs).Case in point, after a quarter century of work with TILs and LAKs struggling to meet utilitarian endpoints, enter gain-of-function CAR engineering, and thus history is made.The same paradigm of cell gain-of-function genetic enhancement can readily be applied to alternate somatic cell platforms think MSCs and iPSCs with a limitless potential to improve clinical outcomes for acute and chronic ailments.

Id like to emphasize three milestones. First, the commercialization of gene therapies in general. The efficacy and safety have improved a lot since the 1990s.

Secondly, the explosion of immunotherapies. Onco-hematology has become a major opportunity for patients with otherwise lethal blood cancers.

Finally, the advances in gene editing technologies. These have opened the door to new therapies which we would have considered utterly incredible a few years ago.

The recent approval for Yescarta in second-line (2L) relapsed/refractory large B-cell lymphoma (LBCL) means that an order-of-magnitude more patients just became eligible for potentially curative therapies. One recent industry insight from Celltelligence suggested that moving from 3L to 2L will potentially double the targetable population in diffuse LBCL alone for CAR T cell therapy. As cell therapies move up the treatment paradigm and cell-based therapeutics are eventually approved to treat a range of cancers, the spotlight will turn (again) to manufacturing capacity. At Cellares, our belief is that high-throughput, end-to-end automation is set to revolutionize cell therapy manufacturing, allowing us to deliver more doses at lower cost to meet the demand. Its a truly exciting time for our industry!

The success of the CAR T cell therapy approach and how it has led to cures for childhood leukemias and lymphomas is an amazing story. Thanks to these incredible advances, kids who would no longer be here today are now effectively cured, and are going to live long, relatively healthy lives without suffering the long-term side effects of traditional chemotherapy and radiation. By allowing investigators to be highly creative in developing this approach, a fascinating new treatment process was developed, for both autologous and allogeneic CAR T cell therapies. Now, an entire industry has been born from utilizing patients and donors stem cells and a modified version of the AIDS virus to cure leukemia. This is truly a mind-blowing advancement that combines so many complex processes and biologics and really showcases the power of creative investigators to come up with amazing new treatment solutions.

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The Biggest CGT Breakthroughs Through the Eyes of Our 2022 Power List - The Medicine Maker

The School of Medicine has named Mariano A. Garcia-Blanco, MD, PhD, as the next chair of its Department of Microbiology, Immunology and Cancer Biology

The School of Medicine has recruited Mariano A. Garcia-Blanco, MD, PhD, an internationally recognized expert in virology and RNA biology, to lead its Department of Microbiology, Immunology and Cancer Biology.

Dr. Garcia-Blanco is a nationally recognized researcher in helping the scientific community better understand gene expression in viruses, and he combines that knowledge with deep experience as both an educator and the leader of a department, said Melina R. Kibbe, MD, the dean of the UVA School of Medicine and chief health affairs officer for UVA Health.Together with this skills and background, he has a clear vision for a department that is conducting cutting-edge research of vital importance.

Garcia-Blanco comes to UVA from the University of Texas Medical Branch, where he has served as chair of the Department of Biochemistry and Molecular Biology since September 2014. A founder of five biotechnology companies and holder of over 11 patents, Garcia-Blanco is a member of the United Nations Council of Scientific Advisers for the International Centre for Genetic Engineering and Biotechnology, and he has previously been a member of the National Institutes of Healths National Advisory General Medical Sciences Council. He has also been elected to the Association of American Physicians and named a fellow of the American Association for the Advancement of Science, the American Academy of Microbiology, and the American Academy of Arts and Sciences.

Continuously funded by the NIH since the early 1990s, Dr. Garcia-Blanco has co-authored more than 190 peer-reviewed scientific publications. His research has focused on how the interactions between proteins and RNA regulate gene expression in cells and viruses. His projects have ranged from examining ways to dial the immune system down in autoimmune diseases and up in cancer to identifying new targets to treat diseases caused by flaviviruses, such as yellow fever, Zika and West Nile. His work has also shed important light on multiple sclerosis and other autoimmune disorders.

As an educator, Dr. Garcia-Blanco has been educating undergraduate, graduate and medical students on topics such as gene regulation, nucleic acids, cancer biology, and autoimmunity, among others.He has mentored over 20 doctoral students and 40 postdoctoral fellows throughout his career and fostered the career development of countless junior faculty.Along with his research and teaching at the University of Texas Medical Branch, he is an adjunct professor of emerging infectious diseases at Duke-NUS Medical School in Singapore. Before coming to Texas, Garcia-Blanco was a faculty member at Duke University from 1990 to 2014.

Our excellent faculty in the Department of Microbiology, Immunology and Cancer Biology will benefit greatly from Dr. Garcia-Blancos inclusive, servant leadership, Kibbe said.I also look forward to seeing how his research continues to help the world better understand both fundamental biology and human disease.

Garcia-Blanco earned his bachelors degree from Harvard University and his MD and PhD from Yale University. He also completed a fellowship at Massachusetts Institute of Technology before joining Duke University.

I am thrilled to be joining the Department of Microbiology, Immunology and Cancer Biology, the School of Medicine, and the University of Virginia, and honored to work with them to achieve excellence in biomedical sciences for the common good, Garcia-Blanco said.

He succeeds Amy Bouton, PhD, who had served as interim chair of the Department since October 1, 2021. Her commitment and dedication to the department has been clear to all and very much appreciated.

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Leading Virus Researcher to Chair UVA's Department of Microbiology, Immunology and Cancer Biology - UVA Health Newsroom

In 1976, a letter to the editor thanked this publication for its coverage of the genetic disease Tay-Sachs, and for regularly promoting opportunities to get tested.

At the time, Tay-Sachs remained a scourge in the Jewish community. Since then, in a victory of community willpower over genetic destiny, a concerted push for early testing has virtually eradicated the disease reducing the number of Ashkenazi children born with Tay-Sachs from 60 per year, to 3 to 5 per year.

But while the incidence of Tay-Sachs among Ashkenazi Jews has fallen, a host of genetic disorders still threatens the community, necessitating genetic screening.

We need to plan and be proactive about it, said Estie Rose, a genetic counselor with JScreen, an Atlanta-based nonprofit that offers testing and education.

In 2008, the U.S. Senate named September Tay-Sachs Awareness Month, but Tay-Sachs is only one of the genetic diseases for which Ashkenazi Jews are more likely to carry a recessive gene. (A recessive gene, as opposed to a dominant one, is expressed only when inherited from both parents.)

According to Rose, about 75 percent of those with Ashkenazi Jewish heritage carry a recessive gene for at least one of a number of genetic conditions. Besides Tay-Sachs, the most common include Gaucher disease, cystic fibrosis, familial dysautonomia and Canavan disease. (According to the Jewish Genetic Disease Consortium, there are also various genetic diseases that are more prevalent among Sephardic Jews.) One in 30 Ashkenazi Jews carries the gene for Tay-Sachs, while among the general population, 1 in 300 is a carrier (the number is also high among those of Cajun descent).

While a recessive gene does no harm, a child with Tay-Sachs is more likely to be born to a couple who are both Ashkenazi Jews.

Its really only a problem if the person youre having a child with has the same gene, explained Mary Norton, an MD and professor of perinatal medicine and genetics at the University of California, San Francisco.

The reason Ashkenazi people are more likely to carry the Tay-Sachs gene is interwoven with the many calamities in the history of the Jewish people. Think the Crusades; think the Holocaust; think the Spanish Inquisition, Rose said. The size of the community shrunk, then it regrew.

For genetics, such circumstances exemplify a population bottleneck and the founder effect. In laypersons terms: Many Jews were killed at various times in history, leaving a smaller pool of genes to replenish the population. Also, Jews in Europe were endogamous, meaning they tended to marry other Jews.

The mutations become copy and pasted over and over and over again, Rose said.

Tay-Sachs was discovered toward the end of the 19th century, and even back then its prevalence among Ashkenazi Jews was noted.

The most common form becomes noticeable in infants around 6 months old. Symptoms include reduced vision and an exaggerated startle response, and then progress to slow growth, listlessness, neural degeneration and seizures by age 2, with death coming by age 5. The disease has no cure.

A carrier of a genetic disorder may have no family history of the disease or have the disease themselves. Pregnancy is often the first time many people get tested to see if they are carriers for a range of genetic disorders. Some dont get tested at all.

JScreens mission is to encourage people not to wait until pregnancy to get tested.

Thats what Rose did, and it changed her life. While in college, she and her partner got tested to see which genetic disorders they carried. It turned out they were both carriers for cystic fibrosis, a life-threatening disease. If shed had children with her then-partner, they could have faced some tough choices.

We decided to break up and avoid all of those things, she said.

Today, as a genetic counselor, Rose helps couples consider their options when faced with similar scenarios. She said JScreen tests for 225 diseases and works closely with the primary health care provider and genetic counselors.

I can serve my own community, which is really important to me, she said. The Jewish community unfortunately faces a lot of genetic health issues.

About 75 percent of those with Ashkenazi Jewish heritage carry a recessive gene for at least one of a number of genetic conditions.

Rose said if a pregnant couple finds they both carry the same disease gene, the next step is to test the fetus. If the fetus has the disorder, the couple has to choose whether or not to carry the baby to term. Even better is to do the testing before pregnancy, Rose said: In case there is a problem, they have more options.

The couple can explore IVF (in which each embryo can be tested before implantation) or egg donation, or they may decide not to have children or even go their separate ways, as Rose and her then-partner did.

Sophia Pesotchinsky is all in favor of testing before pregnancy. Her daughter Vera, 49, has Late Onset Tay-Sachs, a rare form of the disease.

The Pesotchinskys came to the Bay Area from Russia in 1976. Vera later developed motor function problems that turned out to be the first signs of LOTS. Sophia had never been tested to see if she was a carrier, neither in Russia nor here in the U.S. when she was considering having more children. Thats a huge oversight, she said.

If people have come from a different country, they have to be asked, Did you have that test? she said.

Thats particularly true for people who come from the former Soviet Union. Very often they didnt know they had Jewish roots, she pointed out.

Sophia said it took more than a decade to diagnose Vera (along the way, Sophia was told that her daughters problems, ranging from slurring to klutziness, came from having an overbearing immigrant mother). Vera, who earned an MBA from Santa Clara University and a BA from Wellesley College, is currently in a wheelchair and cannot live alone, but mother and daughter are active in patient advocacy through the National Tay-Sachs and Allied Diseases Association.

JScreen isnt the only Jewish organization trying to get people to screen early.

New York-based Dor Yeshorim screens potential couples in the Orthodox community by running tests for over 50 diseases. According to their most recent quarterly report, of more than 9,000 people who have used the service, 120 were found to be genetically incompatible.

Like JScreen, Dor Yeshorim advises people to get tested well before pregnancy. When a match is suggested its time for a compatibility check. Dor Yeshorim, rabbanim and experienced shadchanim urge everyone to check compatibility before a couple or the parents meet to avoid unnecessary heartache! the site says.

To that end, Dor Yeshorim often tests at Orthodox schools. JScreen works with Hillel and Birthright, Rose said.

Advances mean that genetic tests once reserved for Ashkenazi Jews can now be accessed by the population at large, further reducing the likelihood that children will be born with a disease like Tay-Sachs.

Tests used to cover only 25 or so gene disorders, but now hundreds can be identified.

Rose said its important to test no matter what ethnicity you are. While Ashkenazi Jews have their own set of risks, other ethnic groups have theirs. You never know what a test result will bring, Rose noted.

We all have things we dont know about our family history, she said.

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Work remains on Tay-Sachs and other Ashkenazi genetic disorders J. - The Jewish News of Northern California

Newswise The first large-scale genomic study of musicality published on the cover of todays Nature Human Behaviour identified 69 genetic variants associated with beat synchronization, meaning the ability to move in synchrony with the beat of music.

An international team of scientists, including the Vanderbilt Genetics Institute and 23andMe, demonstrated that human capacity to move in synchrony with a musical beat (termedbeat synchronization) is partially coded in the human genome.

Many of the genes associated with beat synchronization are involved in central nervous system function, including genes expressed very early in brain development and in areas underlying auditory and motor skills, according to co-senior author Reyna Gordon, PhD, associate professor in the Department of Otolaryngology - Head and Neck Surgery and co-director of the Vanderbilt Music Cognition Lab.

Rhythm is not just influenced by a single gene, it is influenced by many hundreds of genes, Gordon said. Tapping, clapping and dancing in synchrony with the beat of music is at the core of our human musicality.

The studyalso discovered that beat synchronization shares some of its genetic architecture with other traits, including biological rhythms such as walking, breathing and circadian patterns.

This is novel groundwork toward understanding the biology underlying how musicality relates to other health traits, said co-senior author Lea Davis, associate professor of Medicine.

23andMes large research dataset provided study data from more than 600,000 customers who consented to participate in research allowed researchers to identify genetic alleles that vary in association with participants beat synchronization ability.

The large number of consented study participants offered a unique opportunity for our group to capture even small genetic signals, said David Hinds, PhD, a research fellow and statistical geneticist at 23andMe. These findings represent a leap forward for scientific understanding of the links between genetics and musicality.

First author Maria Niarchou, PhD, research assistant professor in the Department of Medicine, said the study findings made new connections between the genetic and neural architecture of musical rhythm, thus improving our understanding of how our genomes tune our brains to the beat of the music.

The work was supported in part by an NIH Directors New Innovator award #DP2HD098859. Visit the FAQ of the study to learn more.

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Study Shows Genetic Link to Moving to the Beat of Music - Newswise

The Republican Party has created quite a political and scientific mess in its chaotic and contradictory legislative maneuverings in the wake of the overturning of Roe v Wade. Sen. Lindsey Graham spent much of the last weekdefending his proposed federal ban on all abortionsafter 15 weeksa law that also allows any state to set even more restrictive standard, including refusing to allow a woman to terminate a pregnancy in cases of incest or to protect her health.

The proposal was seen by many as an attempt to deflect growing concerns that Republicans are out of step with most Americans who want to preserve some version of choice in every state.

Grahams proposal to try to deflate the backlash against Dobbs has drawn criticism and even ridicule from the right and the left, both of whom call it ham-handed but for different reasons.

Senate Minority Leader Republican Mitch McConnell, referencing the ban, said that most of the members of my conference prefer that this be dealt with at the state level which in Republican-dominated states mostly means complete bans even in cases of incest or health complications.

Democrats were no less incensed. House speaker Nancy Pelosi called Grahams proposal the latest, clearest signal of extreme MAGA Republicans intent to criminalize womens health freedom in all 50 states and arrest doctors for providing basic care. Make no mistake: if Republicans get the chance, they will work to pass laws even more draconian than this [Graham] bill just like the bans they have enacted in states like Texas, Mississippi and Oklahoma.

The over-riding issue for most Americans is government overreach, once a sacred conservative principle: Republicans are increasingly inserting of the government into the private relationship between patients and their clinicians in guiding health decisions, says the American College of Obstetrics and Gynecology in a joint statement representing more than 75 health care organizations:

Abortion care is safe and essential reproductive health care. Keeping the patientclinician relationship safe and private is essential not only to quality individualized care but also to the fabric of our communities and the integrity of our health care infrastructure. As leading medical and health care organizations dedicated to patient care and public health, we condemn this and all interference in the patientclinician relationship.

Ive published 38 editions of several college life science textbooks since 1982. All have covered human prenatal development and assisted reproductive technologies (ARTs).

My books have chronicled the progress in reproductive medicine: from Louise Joy Brown, the first test tube baby; through the fading of amniocentesis as checking circulating fetal DNA offered a far less invasive way to detect extra chromosomes; to selecting the earliest embryos for one or two free of a familys disease-causing mutation, circumventing a lethal legacy.

Im now revising the final chapter of the fourteenth edition of my human genetics textbook, entitled Reproductive Technologies. Its a crazy time to be doing that.

I read most of the decision, to reach my own conclusions. I was astonished at how profoundly the justices skirt the health field that bloomed into existence with Louise Joy Brown four decades ago. I dont pretend to know anything about the law. How can the justices presume medical expertise in telling a woman what she can and cannot do to her body, with such hubris?

The tone of the Supreme Court decision stunningly evokes the thinking of another century and I dont mean the twentieth.

About halfway through the213 pages, seeing no words from modern reproductive medicine, I started doing word searches to speed things up.

A search forin vitro fertilization called up one mention, but in the dissent. Actual. Medical. Facts.

Further, the Court may face questions about the application of abortion regulations to medical care most people view as quite different from abortion. What about the morning-after pill? IUDs? In vitro fertilization? And how about the use of dilation and evacuation or medication for miscarriage management?

Next I searched for a fundamental distinction in developmental biology: embryo versus fetus.

Embryogets 3 hits in the decision. The first is part of embryology in a footnote. More telling is the second mention, part of a quote within a quote (In contemplation of law life commences at the moment of quickening, at that moment when the embryo givesthe first physical proof of life, no matter when it first received it, emphasis added). Thats from an 1872 decision The third mention of embryo is as part of Embryos in the title of a paper cited in a footnote. Not a lot of coverage.

Embryos by definition do not yet have rudiments of all body parts. The period of the embryo extends from fertilization (aka conception) to the end of the 8th week. Obstetricians and politicians count the weeks from the last menstrual period, which tacks on two non-pregnant weeks at the start. Maybe thats because 40 weeks is easier to remember than 38 weeks. More likely, perhaps the erroneous timetable is a legacy from when most obstetricians and politicians were people who could not become pregnant.

In the decision, a word search for fetus brings 54 hits, compared to the 3 indirect ones for embryo, although most abortions are in fact done on embryos. The 2019CDC Abortion Surveillance finds that the majority of abortions took place early in gestation: 92.7% performed at 13 weeks gestation; a smaller number of abortions (6.2%) at 1420 weeks gestation, and even fewer (<1.0%) at 21 weeks gestation.

Next I searched for terms familiar to people seeking reproductive health care. It was enlightening.

First, I looked for mention of some stages of early development beyond the familiar embryo and fetus:

0 hits each for zygote, blastocyst, and inner cell mass.

Then I looked for ARTs other than the lone IVF mention:

0 hits each for gamete intrafallopian transfer (GIFT), preimplantation genetic diagnosis (PGD), and zygote intrafallopian transfer (ZIFT).

I began to think of Dean Wormers comment to John Belushis character Bluto Blutarsky in Animal House abouthis grade point average: Mr. Blutarsky. ZERO POINT ZERO.

The decision mentions the stages of prenatal development in very vague terms, focusing at great length on quickening, when a woman first feels fetal movement. Its all from an historical perspective. And that is a part of pregnancy that a man might imagine. He might wax less sentimental over the barfing, exhaustion, back pain, and labor.

What terrifies me the most is that repealing Roe v Wade doesnt affect just those seeking abortion services. Consider a woman having a miscarriage.

My word search for miscarriage brought up 66 references to the phrase procure the miscarriage.The two instances of produce abortion or miscarriage reveal that procure the miscarriage is doublespeak for abortion. Thats dangerous, because the two drugs used to safely manage a miscarriage are the same used to induce abortion. Ditto the scraping of the uterine lining. The dissent reminds of these facts.

What effect will the decision have on a woman experiencing a spontaneous abortion in a state that doesnt allow the treatment she needs? Will a woman in those states entering a clinic with bleeding and cramping become a criminal suspect? In Alabama, for example, performing an abortion is a Class A felony a provider faces from 10 to 99 years in prison. InTexas, treating infection in a pregnant woman may be delayed because doctors fear punishment, even if they know that live birth is impossible, risking septicemia or even death of the woman.

No one facing a medical crisis should have to fear their physician pausing, or even halting, when in the midst of doing what the patient needs in order to resolve or avoid the threat of prosecution, said Jen Villavicencio, MD, representing the American College of Obstetricians and Gynecologists. Imagine that happening during cardiac bypass or an appendix removal. Or vasectomies, which are unsurprisingly on the rise in the wake of the decision.

Villavicencio also questions the judges expertise to rule on medical matters, reaching the same conclusions that I did:

The individuals writing these laws are not medical experts. Laws like abortion restrictions and bans are not based in science or evidence and, therefore, the language does not coincide within the practice of the highest quality, evidence-based care. The language is often incorrect, not clinically meaningful, and therefore confusing to those practicing medicine Pregnancy, complications of pregnancy, and the treatment of those complexities require nuanced, individualized caresomething that is very difficult when faced with unscientific, non-medical laws.

In vitrofertilization is also complex, requiring nuanced, individualized care. Its painful (daily injections) and drawn out over weeks, with a few months off between attempts. Several embryos must be created in order for one or sometimes two to divide enough times to transfer to a womans uterus. The embryo then is a blastocyst, a hollow ball of cells not the comma-shaped tiny humanoid that some might envision, nor the magnified, mangled fetuses that festoon anti-abortion placards meant to terrorize women at a traumatic time of their lives.

In an increasingly common procedure done with IVF to up the odds of success, a blastocyst cell is removed and tested for mutant genes. If its free of the mutation, the remaining still-microscopic blob is transferred to the womans uterus. This procedure is called preimplantation genetic diagnosis, or PGD.

The first case of IVF with PGD enabled a family to conceive a child who did not inherit the cystic fibrosis that both parents carried. That was 30 years ago.

Extra embryos generated through IVF, with or without PGD, may be donated to other women, for research, discarded, or frozen. More than a millionhuman embryos are currently frozen. Whats to be done with the ones in states where women cant choose what happens to their bodies? Charge the women with a crime? Charge the men, who contributed one genome copy to each cell of each embryo on ice? Fine them? Lock them up? Or defrost thousands of embryos in suspended animation? Then what?

Katie Moser has the mutation that causes Huntingtons disease. She wants to have a child that doesnt inherit the mutant gene, and IVF with PGD could make that happen.

TheNew York Timeshas chronicled Katies experience and shes told her story as an advocate for people with movement disorders. Shell likely develop symptoms before age 50. She turns 41 on July 14 also Woody Guthries birthday, perhaps the most famous person to have HD.In 2011, Katie underwent two rounds of IVF. Eighteen embryos resulted, eight viable. But they all had inherited the HD gene.

HD is dominant, so the embryos arent just carriers. Theyre destined, and so hold clues to the earliest manifestations of the disease. Thats why Katie donated them for research a decade ago to researchers in another state. How will the abortion decision affect the transport of genetically-doomed frozen IVF embryos? Will flights need to be rerouted over states with more liberal laws, like people carrying cannabis on planes, avoiding the forbidden zones? That may sound like the Planet of the Apes, but its what the US is becoming, in terms of reproductive rights: a mosaic of forbidden zones.

Katie Moser had genetic testingbecause she knew she has a family history of a single-gene disease. Millions of pregnant women have geneticscreening, which means without such a history, with a simple blood test,NIPT(noninvasive prenatal testing).

NIPT is done after 9 weeks, in obstetric-speak. If the number of fetal DNA pieces corresponding to a chromosome far exceeds or is below the number of maternal pieces, then the fetus has an extra or missing chromosome, respectively.

The test has replaced much more invasive amniocentesis and chorionic villus sampling. A bad result an extra chromosome 13 or 18, for example, which rarely leads to a live birth brings up the choice to end the pregnancy. Will overturning Roe force women in some states to endure a pregnancy with a near 100 percent likelihood of ending in tragedy? Yes.

The dissenting opinion from justices Breyer, Sotomayor, and Kagan directly addresses the issue of a fetus with a hopeless diagnosis:

So too, after todays ruling, some States may compel women to carry to term a fetus with severe physical anomaliesfor example, one afflicted with Tay-Sachs disease, sure to die within a few years of birth.

Again, medical facts and details.

I looked through the final chapter of my human genetics textbook, Reproductive Technologies. I will not allow the Roe v Wade reversal to impact my coverage of this essential information.

The chapter opening case history is true, about a couple seeking IVF with PGD to select an embryo free from the devastating brain disease for which they are each carriers, as well as for a clotting abnormality the man has. If they select a disease-free embryo, what will happen to the others?

The first section of the chapter discusses savior siblings, relating the famous story of Adam Nash. He was chosen, as an 8-celled-embryo, to be transferred to his mother-to-bes uterus so that he could eventually donate umbilical cord stem cells to save his 6-year-old sister Molly from Fanconi anemia. Adam did not inherit the mutant genes and was a perfect tissue match for Molly. He was born in 2000 this technology is hardly too new for the justices to be unaware.

After the section on IVF, my book covers the aforementioned GIFT and ZIFT. Both are used to treat infertility.

In GIFT, a few eggs are retrieved and introduced with sperm into a fallopian tube, past a blockage. Fertilization takes place in vivo, so theres nothing to outlaw. (And of course donating eggs is painful; donating sperm, well, not so much.)

In ZIFT, sperm meet eggs in a dish, like regular IVF, and then a fertilized ovum is placed into the tube. In regular IVF, it divides a few times first.

So, a physician who fumbles and drops the pipette bearing the precious cargo of GIFT is just making a mess. But a physician who drops the pipette bearing a fertilized ovum is committing murder, ending the life of an unborn child, albeit one who is just one cell.

The slippery slope that comes with this archaic, religion-tainted Supreme Court decision is going to cost many postnatal lives.

The dissenting opinion sums up the situation:

The majoritys refusal even to consider the life-altering consequences of reversing Roe and Casey is a stunning indictment of its decision. With sorrowfor this Court, but more, for the many millions of American women who have today lost a fundamental constitutional protectionwe dissent.

Ricki Lewis has a PhD in genetics and is a science writer and author of several human genetics books.She is an adjunct professor for the Alden March Bioethics Institute at Albany Medical College.Follow her at herwebsiteor Twitter@rickilewis

A version of this article was originally posted atPLOSand has been reposted here with permission. PLOS can be found on Twitter@PLOS

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Viewpoint: In the post Roe v Wade world, what changes should a biology textbook writer make to address the medical repercussions of Dobbs? - Genetic...

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the European Commission (EC) has granted marketing authorization for AMVUTTRA (vutrisiran), an RNAi therapeutic for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy. The EC approval is based on positive 18-month results from the HELIOS-A Phase 3 study, where AMVUTTRA significantly improved the signs and symptoms of hATTR amyloidosis, with more than 50 percent of patients experiencing halting or reversal of their polyneuropathy manifestations.

On behalf of patients across Europe, we could not be prouder to announce the approval of AMVUTTRA, our second RNAi therapeutic for hATTR amyloidosis. We are committed to delivering continued innovation to people affected by rare, life-limiting conditions where high unmet need still exists. Todays decision now means we can progress working with health authorities across Europe to achieve responsible and sustainable access arrangements that allow us to bring AMVUTTRA to patients as quickly as possible. Our thanks go to the patients, families, investigators and study staff who have enabled us to reach this significant milestone, said Kasha Witkos, SVP, Head International Region at Alnylam.

Although the considerable research into hATTR amyloidosis over the past few years has resulted in a more positive outlook for those diagnosed with the condition, there remain unmet needs in treatment for patients living with this rapidly progressive, multi-system disease, said Professor David Adams, Head of the Neurology department at Bictre hospital AP-HP, University of Paris-Saclay and Lead Investigator for the HELIOS-A Study. RNAi therapeutics are changing the future of medicine and I am honored to have contributed to these research efforts that have enabled us to bring an innovative new medicine to patients. Results from the HELIOS-A study have shown the potential AMVUTTRA has to benefit patients with hATTR amyloidosis with stage 1 or stage 2 polyneuropathy, whilst also helping reduce treatment burden through subcutaneous dosing once every three months.

HELIOS-A was a global, randomized, open-label, multicenter, Phase 3 study that evaluated the efficacy and safety of AMVUTTRA across a diverse group of patients with hATTR amyloidosis with stage 1 or stage 2 polyneuropathy. Results of the HELIOS-A study were published in Amyloid in July, 2022.

In the HELIOS-A study, AMVUTTRA met the primary and all secondary endpoints of the study at both 9 months and 18 months, demonstrating reversal in neuropathy impairment and an encouraging safety and tolerability profile. AMVUTTRA demonstrated improvement in the mean change from baseline in modified Neuropathy Impairment Score + 7 (mNIS+7) at 18 months (the primary endpoint for the EU), as compared to external placebo data from the landmark APOLLO Phase 3 study of patisiran.

After 18 months of dosing, the most frequently occurring adverse reactions in AMVUTTRA-treated patients were arthralgia (joint stiffness) and pain in extremity (pain in arms and legs). Other less frequent adverse reactions reported with AMVUTTRA were dyspnea (shortness of breath), injection site reaction and an increase in blood alkaline phosphatase (a liver enzyme).

Vutrisiran was previously granted Orphan Drug Designation in the European Union (EU) and U.S. for the treatment of ATTR amyloidosis and in Japan for transthyretin type familial amyloidosis with polyneuropathy. In June 2022, AMVUTTRA was approved by the U.S. Food and Drug Administration (FDA) for the treatment of the polyneuropathy of hATTR amyloidosis in adults. Vutrisiran is under review by the Brazilian Health Regulatory Agency (ANVISA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).

About AMVUTTRA (vutrisiran)

AMVUTTRA is an RNAi therapeutic, which is designed to target and silence specific messenger RNA (mRNA), blocking the production of wild-type and variant transthyretin (TTR) protein before it is made. AMVUTTRA utilizes Alnylams Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, designed for increased potency and high metabolic stability to allow for quarterly, and potentially biannual, subcutaneous administration. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy, which encompasses both hereditary ATTR (hATTR) and wild-type ATTR (wtATTR) amyloidosis.

About hATTR Amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is an inherited, progressively debilitating, and fatal disease caused by variants (i.e., mutations) in the TTR gene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. Variants in the TTR gene cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. hATTR amyloidosis represents a major unmet medical need with significant morbidity and mortality affecting approximately 50,000 people worldwide. The median survival is 4.7 years following diagnosis, with a reduced survival (3.4 years) for patients presenting with cardiomyopathy.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as a major scientific breakthrough that happens once every decade or so, and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylams RNAi therapeutic platform, function upstream of todays medicines by silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

IMPORTANT SAFETY INFORMATION

Reduced Serum Vitamin A Levels and Recommended Supplementation

AMVUTTRA treatment leads to a decrease in serum vitamin A levels. Supplementation of approximately, but not exceeding, 2500 IU to 3000 IU vitamin A per day is advised for patients taking AMVUTTRA. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

Adverse Reactions

The most frequently occurring adverse reactions in patients treated with AMVUTTRA were arthralgia and pain in extremity. Other commonly reported adverse reactions with AMVUTTRA were dyspnoea, injection site reaction and increase in blood alkaline phosphatase.

About Alnylam Pharmaceuticals

Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the potential treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylams has developed RNAi therapeutic products which are licensed for the treatment of hATTR amyloidosis, acute hepatic porphyria, primary hyperoxaluria type 1 and primary hypercholesterolemia / mixed dyslipidemia. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its Alnylam P5x25 strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA.

Alnylam Forward Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylams views with respect to the safety and efficacy of AMVUTTRA, a quarterly subcutaneous injection, for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, the potential of AMVUTTRA to significantly improve the signs and symptoms of polyneuropathy, and potentially halt or reverse disease manifestations for some patients, the potential of AMVUTTRA to help reduce treatment burden through subcutaneous dosing once every three months, plans to progress working with health authorities across Europe to achieve responsible and sustainable access arrangements to bring AMVUTTRA to patients as quickly as possible, continued regulatory review of vutrisiran in multiple jurisdictions, and Alnylams aspiration to become a leading biotech company and the planned achievement of its Alnylam P5x25 strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylams business, results of operations and financial condition and the effectiveness or timeliness of Alnylams efforts to mitigate the impact of the pandemic; the potential impact of the recent leadership transition on Alnylams ability to attract and retain talent and to successfully execute on its Alnylam P5x25 strategy; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates; actions or advice of regulatory agencies and Alnylams ability to obtain and maintain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally, including AMVUTTRA; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylams ability to successfully expand the indication for ONPATTRO, AMVUTTRA and OXLUMO in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylams ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential impact of current and the risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the Risk Factors filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

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Alnylam Receives Approval in Europe for AMVUTTRA (vutrisiran) for the Treatment of Hereditary Transthyretin-mediated (hATTR) Amyloidosis in Adult...