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Archive for the ‘Genetic medicine’ Category

Common brain malformation traced to its genetic roots – Washington University School of Medicine in St. Louis

Saturday, January 2nd, 2021

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Discovery could aid early screening, shed light on how Chiari malformation arises

The lowest part of a child's brain is visible below the bottom of the skull in this MRI scan and shows evidence of a Chiari 1 malformation. Researchers at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes linked to brain development, and that children with large heads are at increased risk of developing the condition.

About one in 100 children has a common brain disorder called Chiari 1 malformation, but most of the time such children grow up normally and no one suspects a problem. But in about one in 10 of those children, the condition causes headaches, neck pain, hearing, vision and balance disturbances, or other neurological symptoms.

In some cases, the disorder may run in families, but scientists have understood little about the genetic alterations that contribute to the condition. In new research, scientists at Washington University School of Medicine in St. Louis have shown that Chiari 1 malformation can be caused by variations in two genes involved in brain development.

The condition occurs when the lowest parts of the brain are found below the base of the skull. The study also revealed that children with unusually large heads are four times more likely to be diagnosed with Chiari 1 malformation than their peers with normal head circumference.

The findings, published Dec. 21 in the American Journal of Human Genetics, could lead to new ways to identify people at risk of developing Chiari 1 malformation before the most serious symptoms arise. It also sheds light on the development of the common but poorly understood condition.

A lot of times people have recurrent headaches, but they dont realize a Chiari malformation is the cause of their headaches, said senior author Gabriel Haller, PhD, an assistant professor of neurosurgery, of neurology and of genetics. And even if they do, not everyone is willing to have brain surgery to fix it. We need better treatments, and the first step to better treatments is a better understanding of the underlying causes.

If people start experiencing severe symptoms like chronic headaches, pain, abnormal sensations or loss of sensation, or weakness, the malformation is treated with surgery to decompress the Chiari malformation.

Theres an increased risk for Chiari malformations within families, which suggests a genetic underpinning, but nobody had really identified a causal gene, Haller said. We were able to identify two causal genes, and we also discovered that people with Chiari have larger head circumference than expected. Its a significant factor, and easy to measure. If you have a child with an enlarged head, it might be worth checking with your pediatrician.

To identify genes that cause Chiari 1 malformation, Haller and colleagues sequenced all the genes of 668 people with the condition, as well as 232 of their relatives. Of these relatives, 76 also had Chiari 1 malformation and 156 were unaffected. The research team included first author Brooke Sadler, PhD, an instructor in pediatrics, and co-authors David D. Limbrick, Jr., MD, PhD, a professor of neurosurgery and director of the Division of Pediatric Neurosurgery, and Christina Gurnett, MD, PhD, a professor of neurologyand director of the Division of Pediatric and Developmental Neurology, among others.

Sequencing revealed that people with Chiari 1 malformation were significantly more likely to carry mutations in a family of genes known as chromodomain genes. Several of the mutations were de novo, meaning the mutation had occurred in the affected person during fetal development and was not present in his or her relatives. In particular, the chromodomain genes CHD3 and CHD8 included numerous variants associated with the malformation.

Further experiments in tiny, transparent zebrafish showed that the gene CHD8 is involved in regulating brain size. When the researchers inactivated one copy of the fishs chd8 gene, the animals developed unusually large brains, with no change in their overall body size.

Chromodomain genes help control access to long stretches of DNA, thereby regulating expression of whole sets of genes. Since appropriate gene expression is crucial for normal brain development, variations in chromodomain genes have been linked to neurodevelopmental conditions such as autism spectrum disorders, developmental delays, and unusually large or small heads.

Its not well known how chromodomain genes function since they have such a wide scope of activity and they are affecting so many things at once, Haller said. But they are very intriguing candidates for molecular studies, to understand how specific mutations lead to autism or developmental delay or, as in many of our Chiari patients, just to increased brain size without cognitive or intellectual symptoms. Wed like to figure out the effects of each of these mutations so that in the future, if we know a child has a specific mutation, well be able to predict whether that variant is going to have a harmful effect and what kind.

The association between chromodomain genes and head size inspired Haller and colleagues to measure the heads of children with Chiari malformations, comparing them to age-matched controls and to population averages provided by the Centers for Disease Control and Prevention. Children with Chiari tended to have larger than average heads. Those children with the largest heads bigger than 95% of children of the same age were four times more likely to be diagnosed with the malformation.

The findings suggest that children with larger heads or people with other neurodevelopmental disorders linked to chromodomain genes may benefit from screening for Chiari malformation.

A lot of kids that have autism or developmental disorders associated with chromodomain genes may have undiscovered Chiari malformations, Haller said. The only treatment right now is surgery. Discovering the condition early would allow us to watch, knowing the potential for serious symptoms is there, and perform that surgery as soon as its necessary.

Sadler B, Wilborn J, Antunes L, Kuensting T, Hale AT, Gannon SR, McCall K, Cruchaga C, Harms M, Voisin N, Reymond A, Cappuccio G, Burnetti-Pierri N, Tartaglia M, Niceta M, Leoni C, Zampino G, Ashley-Koch A, Urbizu A, Garrett ME, Soldano K, Macaya A, Conrad D, Strahle J, Dobbs MB, Turner TN, Shannon CN, Brockmeyer D, Limbrick DD, Gurnett CA, Haller G. Rare and de novo coding variants in chromodomain genes in Chiari I malformation. American Journal of Human Genetics. Dec. 21, 2020. DOI: 10.1016/j.ajhg.2020.12.001

This study was funded by Sam and Betsy Reeves and the Park-Reeves Syringomyelia Research Consortium; the University of Missouri Spinal Cord Injury Research Program; the Childrens Discovery Institute of St. Louis Childrens Hospital and Washington University; the Washington University Institute of Clinical and Translational Sciences, grant number UL1TR000448 from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH); the Eunice Kennedy Shriver National Institute of Child Health & Human Development, award number U54HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University; the Swiss National Science Foundation, grant number 31003A_182632; and the Jrme Lejeune Foundation.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Common brain malformation traced to its genetic roots - Washington University School of Medicine in St. Louis


Dawn Wells, Mary Ann on Gilligans Island, Dies at 82 – The New York Times

Saturday, January 2nd, 2021

Dawn Wells, the actress who radiated all-American wholesomeness, Midwestern practicality and a youthful nave charm as the character Mary Ann on the hit 1960s sitcom Gilligans Island, died on Wednesday at a nursing home in Los Angeles. She was 82.

Her publicist, Harlan Boll, said the cause was related to Covid-19.

Debuting on CBS in 1964, Gilligans Island followed an unlikely septet of day trippers (on a three-hour tour, as the theme song explained) who ended up stranded on a desert island.

There, shipwrecked alongside a movie star (who spent most of her time in evening gowns), a science professor, a pompous, older rich couple, and two wacky crew members was Mary Ann Summers (Ms. Wells), a farm girl from Kansas who had won the trip in a local radio contest.

The character had a relatively scant back story it was said that she worked at the hardware store back home and had a boyfriend but Mary Anns persona alone made her memorable. Gingham blouses, short shorts, double ponytails and perky hair bows were all parts of her signature look.

The first version of the shows theme song mentioned five of the characters and the rest, but the lyrics were soon changed to name the professor (Russell Johnson) and Mary Ann as well. The others in the cast were Bob Denver (Gilligan), Alan Hale Jr. (the Skipper), Jim Backus and Natalie Schafer (as the couple Thurston Howell III and Lovey Howell), and Tina Louise (as the actress, Ginger). Ms. Louise is the last surviving member of the original cast.

That the premise of Gilligans Island was pretty much implausible and its humor simplistic made no difference to the shows millions of fans or its producers, who would discover in the years to come that they had spawned a cultural phenomenon.

Though Gilligans Island lasted only three seasons, canceled in 1967, it hardly slipped from the horizon. Endless reruns ensued, and the cast members had a series of encore performances. Ms. Wells, for one, reprised her role as Mary Ann in three reunion TV movies: Rescue From Gilligans Island (1978), The Castaways on Gilligans Island (1979) and The Harlem Globetrotters on Gilligans Island (1981).

In 1982, she did the voices of both her character and Ms. Louises movie star for Gilligans Planet, an animated spinoff series. And she went on to play Mary Ann in episodes of at least four other (unrelated) shows: Alf (1986), Baywatch (1989), Hermans Head (1991) and Meego (1997). Gilligans-themed episodes had a certain camp value.

Even her career as an author related directly to the series. Mary Anns Gilligans Island Cookbook, which included Skippers Coconut Pie, was published in 1993. What Would Mary Ann Do? A Guide to Life, a memoir she wrote with Steve Stinson, appeared in 2014.

Jan. 2, 2021, 5:13 p.m. ET

Mary Anns advice in the book included this thought: Failure builds character. What matters is what you do after you fail. The San Francisco Book Review called the book a worthwhile mix of classic values and sincerity.

Asked decades later about her favorite Gilligans Island episodes, Ms. Wells mentioned And Then There Were None, which included a dream sequence in which she got to do a Cockney accent. She also cited Up at Bat, an episode in which Gilligan imagined that he had turned into Dracula.

I loved being the old hag, she said.

Dawn Elberta Wells was born in Reno, Nev., on Oct. 18, 1938, the only child of Joe Wesley Wells, a real estate developer, and Evelyn (Steinbrenner) Wells. Dawn majored in chemistry at Stephens College in Columbia, Mo., then became interested in drama and went to the University of Washington in Seattle. She graduated in 1960 with a degree in theater arts and design, having taken some time off to win a state beauty title and compete in the 1960 Miss America pageant.

Big deal, she said in a 2016 interview with Forbes, making light of her Miss Nevada win. There were only 10 women in the whole state at the time.

For the Miss America pageant in Atlantic City, her talent performance was a dramatic reading from Sophocles Antigone.

A 1961 episode of the drama The Roaring Twenties was her screen debut. When she was cast on Gilligans Island, she had appeared onscreen only about two dozen times, mostly in prime-time series, including 77 Sunset Strip (multiple episodes), Surfside Six, Hawaiian Eye, Bonanza and Maverick.

After her television career cooled down, Ms. Wells returned to her first love: theater, doing at least 100 productions nationwide. Her last television role was in 2019, as the voice of a supernatural dentist on the animated Netflix series The Epic Tales of Captain Underpants.

Her last onscreen appearance was in a 2018 episode of Kaplans Korner, about actors running an employment agency. Her only soap opera appearance was in a 2016 episode of The Bold and the Beautiful, in which she played a fashion buyer from a wealthy family.

Ms. Wellss marriage in 1962 to Larry Rosen, a talent agent, ended in divorce in 1967, the same year Gilligans Island went off the air. She is survived by a stepsister, Weslee Wells.

Ms. Wells went on to operate charity-oriented businesses. She was a prominent supporter of the Elephant Sanctuary in Tennessee, the nations largest natural habitat refuge developed for African and Asian elephants.

She also taught acting, creating the nonprofit Idaho Film and Television Institute while living at her ranch in the Teton Valley. But a screen career was never her childhood dream.

I wanted to be a ballerina, then a chemist, she recalled in the Forbes interview. If I had to do it all over again, Id go into genetic medicine.

Alex Traub contributed reporting.

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Dawn Wells, Mary Ann on Gilligans Island, Dies at 82 - The New York Times


This doctor survived COVID-19 during the first wave. Shes one of the experts we turn to for advice. –

Saturday, January 2nd, 2021

Judith Lightfoot was managing her illness herself, until she couldnt.

It felt like a bad flu. She was sick to her stomach. She couldnt eat.

I was passing out all over the house said Lightfoot, who is the interim chairperson for Rowan Universitys department of internal medicine, chief of infectious disease and department director for internal medicine.

This was early March and Lightfoot, who was well aware of the COVID-19 virus sweeping across the world, spent two months battling back from it. Her expertise in the medical field and as a survivor of the coronavirus has made her a valued source for NJ Advance Media and other news outlets.

Lightfoot, 57, is a doctor of osteopathic medicine, which differs from a medical doctor in philosophy. Doctors of osteopathic medicine treat their patients holistically and believe that the body can heal itself.

She was on an international jazz cruise in January with her husband when she heard a BBC news report about the virus overtaking Wuhan, China. Her alarm level increased when she saw what happened at the nursing home in Washington State.

I was criticized for saying we should wear masks early on, she said.

By late February, she was angering more people at the university when she vocally opposed letting students travel abroad, she said.

I felt people were trying to discount what I was saying, they just didnt know and they didnt want to think it was going to be this serious, Lightfoot said.

She attended a gala at the Borgata on March 7 and remembers telling her husband that she had a headache and wanted to leave after the awards. Within days she couldnt eat, couldnt drive and lost a clothing-size worth of weight.

Im an avid spinner and I could barely walk around the block, she said. I couldnt lift 5 pounds. I had lost so much weight and muscle mass.

Lightfoot is a former ballerina. Growing up in the Washington, D.C. area she wanted to be a professional dancer, but her father told her she needed to find a job that would allow her to support herself. She was drawn to science and inspired by a teacher who told stories about her husbands work for NASA.

There was also a push to increase the number of female engineers. Mechanical and electrical engineering didnt interest her, but genetic engineering did. That led her to osteopathic medicine. Shes been at Rowan University for almost three years.

Lightfoot had developed pneumonia from the coronavirus by the time she went to the hospital on March 18. I didnt want to go to the hospital because COVID was there, she said.

It took until July for her to regain her full strength. Ive seen every bit of this, Lightfoot said. How it robs you.

You have to rest. The breathing was the hardest -- and trying to survive, she said

Now, that the second wave is here, Lightfoot wants people to know that the cases are just as serious as the first round -- and people are still dying.

Not everyone understands the science, she said. Some people think youre not talking about them when it comes to wearing the mask.

One of her patients rented out a movie theater for 20 of his friends and family. Seven of those who went now have COVID-19.

People are under this perception that their circle is safe. We know who weve been around, Lightfoot said. No one is safe.

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Allison Pries may be reached at

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This doctor survived COVID-19 during the first wave. Shes one of the experts we turn to for advice. -


Fighting Covid-19 Brought These Lasting Breakthroughs to Science and Medicine – Singularity Hub

Saturday, January 2nd, 2021

2020 was the year of the pandemic. But the arrival of Covid-19 in January not only threw an Earth-sized wrench into our lives, it also dictated the course of scientific discovery. Never before have so much attention, investment, and passion been devoted to one scientific problem. Never before have pre-print servers exploded in popularity, allowing scientists to share discoveries at lightning speed. And never before have we managed to build an arsenal to beat back a life form entirely novel to us, massively accelerating vaccine development by months, if not yearsa true paradigm shift not just in vaccinology, but also in how science is done and communicated under fire.

Yet I dont want to focus solely on Covid-19. Were now in the end game. Last week, the FDA and its Canadian and British equivalents approved the Pfizer-BioNTech mRNA vaccine for emergency use. Modernas mRNA vaccine is hot on its heels, also boasting a success rate of over 90 percent. Front-line workers are receiving the jab all over the country. And dozens of other vaccines are still in the rat race.

Theres no escaping Covid-19 in an end-year retrospective. But theres good reason to look aheadthe biotech and camaraderie that created an entirely new type of vaccine in record pace isnt confined to the pandemic, vaccine research, or infectious diseases. They have the power to completely overhaul medicine.

You might have heard that mRNA vaccines have never previously been approved by the FDA. Yet the science behind them is decades long, courtesy of a young Hungarian-born biologist behind a key mRNA discoveryone so novel and groundbreaking it precipitated the death of her career.

Nearly all lifeforms are built by and run on proteins. But the instructions for building proteins are saved in our genetic material. Think of DNA as a library, and the cells protein-building factory as a far-off facility speaking a different language. mRNA, short for messenger RNA, is the translator that literally moves between our cells DNA library and the protein factory.

In other words, our bodies listen to mRNA to decide which proteins to build. If we could design and synthesize artificial mRNA and deliver them into cells, its possible in theory to hijack our cells own protein-building system to make any protein we wanteven those that are foreign, such as viral proteins.

Thats the reasoning behind both Pfizer-BioNTech and Modernas vaccines. By delivering the mRNA of a viral part into our cells, our bodies will make these proteins. Because these proteins are basically alien invaders, our immune system learns to recognize them and creates a memory of those foes. When it encounters a real infection, the entire immune military of trained antibodies and killer cells can then rapidly spur to life, nixing the invader before they have a chance to spread or reproduce.

Theres a reason mRNA vaccines are so desirable. Compared to traditional protein-based ones, such as those involving dead viruses that need to be grown in chicken embryos (not kidding), mRNA is incredibly easy to scale in production with low costs. This also makes it possible to screen through candidates at super-sonic speedand in a pandemic, speed is everything.

At least, thats the theory on paper. Thanks to recent advances in biotech and Covid-19 lighting sciences behind on fire, mRNA drugs have finally become a widely successful reality.

Broadly speaking, three main technologies have propelled mRNA vaccines to success in the Covid-19 race: whole-genome reading, mRNA design and packaging, and mRNA synthesis.

The first step to combating any viral foe is to know thy enemy. By January 11, Chinese scientists had deposited parts of the viruss genetic blueprint onto GenBank, a highly popular online database for genetic information. Whole-genome sequences soon followed, digitizing the virus and allowing comparisons between its genetic blueprint and other known viruses. Within a month, we knew that the virus belonged to the coronavirus family, allowing scientists to draw upon previous experience with similar virusesSARS, MERSto hone in on the newcomers surface spike proteins, named after their jagged shapes, as a potential vaccine target.

Genetic sequencing soon took the reins. As an offshoot of synthetic biology, a field that reshuffles the building blocks of life, the cost of making artificial genetic sequences has dropped dramaticallyso much so that its now simple to order these molecules through commercial companies at dollars a pop.

Its also made it possible to recreate an entire genome from scratch halfway across the world. A Swiss group, for example, used Chinas data to synthesize SARS-CoV-2s entire genome in the lab, essentially instantly teleporting it into their hands without having to wait for physical samples. Other teams reproduced only the spike protein to analyze for portions that are especially incendiary towards our immune system, which could spark a larger immune response. In early February, long before the world realized wed be in the midst of a pandemic, scientists had already nailed down the sequence and shape of the protein that eventually spurred the development of our newfangled mRNA vaccines.

The next step was finding a weapon against the virusand getting it inside a cell. Thanks to computational alignment tools, figuring out the genetic code for the spike protein was a piece of cake. The harder part was designing mRNA candidates, the instructions, to encode for the spike protein. One frustrating reason why mRNA vaccines have previously failed is because these molecules are extremely fragile. The body, with its relatively high heat and multitudes of molecular-digesting proteins, is a hostile place.

The hostility also goes the other way. Synthetic mRNAs are very foreign to our bodies. Without care, they can trigger the immune system to go into overdrivea dangerous condition that could result in serious problems.

Heres where new tech stood on the shoulders of age-old research. With hopes of making mRNA drugs a reality, scientists have long worked to change their basic componentsletters very similar to DNAs familiar quad squad of A, T, C, and Gwith slightly chemically-improved ones to increase their stability. Other swaps fine-tune the mRNAs efficacy so that it triggers a Goldilocks-like immune responsenot too much, not too little.

Finally, naked mRNA needs to get inside a cell to work. But once it does, its almost instantaneously chopped up. Without mRNA sticking around, our bodies cant make the viral spike protein, hence no immunity. To deliver it into cells, scientists relied on fatty bubblesalso known as lipid nanoparticlesto form a vessel around the mRNA strands. These cellular spaceships are also a gift from the past: back in 2018, the FDA approved their use for delivering another type of RNA molecules. Pfizer-BioNTech and Modernas results provide some of the strongest evidence that they also work well with mRNAs.

The success is indisputable: Moderna went from analyzing the viruss genetic sequence to an experimental jab in the arm in just 63 days. Pfizer-BioNTech broke lightspeed with its vaccine for emergency use in less than a year.

The biotechnologies that made Covid-19 mRNA vaccines are here to stay. So are the fountains of knowledge weve gained from this terrifying trial by fire. From the ins and outs of immune responses to what makes mRNA more stable, less toxic, and easier to deliver, to advances in synthetic biology and seamless global collaboration, the battle against Covid-19 highlights how a decade-long scientific dream just blossomed to fruition.

Covid-19 is only one foe. A similar strategy could now be used, with far more confidence, on our long-battled enemies such as HIV. Even novel vaccines are just a small slice of whats possible. mRNA is the bodys guidebook for building proteinany protein. A synthetic mRNA strand that recognizes certain types of cancer could lead to highly-specific cancer vaccines. BioNTech, for example, reported in 2017 that a vaccine against melanoma, tailor-made to each of its 13 participants unique cancer genetic profile, had higher immunity against their tumors and reduced the chance of spread. Synthetic mRNA could artificially produce missing or defective proteins in the body, such as those critical for normal eyesight or nerve function.

The dream of mRNA therapeutics has been alive since the 90s. One just came true. Keep your eyes peeled for others in 2021.

Image Credit: Felipe Esquivel Reed/Wikimedia Commons

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Fighting Covid-19 Brought These Lasting Breakthroughs to Science and Medicine - Singularity Hub


Vertex Announces New Drug Submission for Investigational Triple Combination Medicine for the Treatment of Cystic Fibrosis Has Been Accepted for…

Saturday, January 2nd, 2021

Dec. 28, 2020 13:04 UTC

BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced its New Drug Submission for TRIKAFTA, Vertexs investigational triple combination medicine, has been accepted for Priority Review by Health Canada for the treatment of cystic fibrosis (CF) in people ages 12 years and older.

We are pleased this submission has been accepted for Priority Review by Health Canada, and we anticipate this accelerated review process will enable access for patients as early as possible, said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex.

With Priority Review, the conventional review timeline of 300 days is reduced to 180 days. The expected approval target by Health Canada is in the first half of 2021.

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people worldwide. CF is a progressive, multi-system disease that affects the lungs, liver, GI tract, sinuses, sweat glands, pancreas and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF. While there are many different types of CFTR mutations that can cause the disease, the vast majority of all people with CF have at least one F508del mutation. These mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working and/or too few CFTR proteins at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the early 30s.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create medicines for people with serious diseases. The company has multiple approved medicines that treat cystic fibrosis (CF) a rare, life- threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 11 consecutive years on Science magazine's Top Employers list and a best place to work for LGBTQ equality by the Human Rights Campaign. For company updates and to learn more about Vertexs history of innovation, visit or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements made by Carmen Bozic in this press release, including expectations for patient access to our medicine, and statements regarding the anticipated timing of the expected approval target by Health Canada. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that the New Drug Submission to Health Canada may not be approved in the expected timeline, or at all, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy or other reasons, and other risks listed under the heading Risk Factors in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at and available through the company's website at You should not place undue reliance on these statements. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.


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The Top 5 Most-Read Precision Oncology Articles of 2020 – Managed Markets Network

Saturday, January 2nd, 2021

In August 2020, the FDA approved the first diagnostic test that combines next-generation sequencing and liquid biopsy. The test is intended to help guide treatment decisions for patients with specific types of mutations of the epidermal growth factor receptor (EGFR) gene in metastatic nonsmall cell lung cancer (NSCLC), which is particularly deadly. The FDA called it a new era for mutation testing. The approval was granted to Guardant360CDx to provide information on multiple solid tumor biomarkers and to help identify EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso), which is approved for a form of metastatic NSCLC.

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4. Dr Andre Goy Discusses What Weve Learned About CAR T Therapies and Cytokine Responses

In a video interview, Andre Goy, MD,chairman, director, and chief of the Division of Lymphoma at John Theurer Cancer Center in Hackensack, NJ,discussed what has been learned from existing chimeric antigen receptor T (CAR T)-cell therapies in managing cytokine responses.

Watch the interview here.

3. OneOncology, Foundation Medicine Create Partnership to Deliver Targeted Care

Also in August 2020, OneOncology, a network of nearly 170 community oncology care sites, and cancer genomic profiling firm Foundation Medicine announced a partnership to give patients and physicians access to genomic profiling tools as well as expanded research opportunities. In addition, OneOncology will help Foundation Medicine to create new assays for community oncology practices.

Read the full article here.

2. Broad Testing for Multiple Genes Benefits Patients With Cancer, Relatives

A study published in JAMA Oncology described how universalmultigene panel testingwas linked with increased detection of actionable, heritable variants beyond what one would expect to find using targeted genetic testing based on current cancer guidelines. The multicenter cohort study found that 1 in 8 patients had a pathogenic germline variant, half of which would not have been found if using guidelines alone. In addition, for the nearly 30% of patients with a high-penetrance variant, the findings led to a change in treatment.

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1. How DNA Medicines Could Transform Treatment of Glioblastoma Multiforme

In an article appearing in the August 2020 edition of Evidence-Based Oncology, Jeffrey Skolnick, MD, the vice president of clinical development at biotech firm Inovio, discusses the companys proprietary technology that uses a computer algorithm to build DNA medicines that can target almost any antigen that can be presented to the human immune system through the major histocompatibility class I system. DNA medicines are built in the form of circular strands of synthetic DNA called plasmids, which can neither propagate nor integrate into the human genome. He also discusses their use in a potential application for glioblastoma, which is incurable.

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The Top 5 Most-Read Precision Oncology Articles of 2020 - Managed Markets Network


NIH study uncovers blood vessel damage and inflammation in COVID-19 patients’ brains but no infection – National Institute on Aging

Saturday, January 2nd, 2021

In an in-depth study of how COVID-19 affects a patients brain, National Institutes of Health researchers consistently spotted hallmarks of damage caused by thinning and leaky brain blood vessels in tissue samples from patients who died shortly after contracting the disease. In addition, they saw no signs of SARS-CoV-2 in the tissue samples, suggesting the damage was not caused by a direct viral attack on the brain. The results were published as a correspondence in the New England Journal of Medicine.

We found that the brains of patients who contract infection from SARS-CoV-2 may be susceptible to microvascular blood vessel damage. Our results suggest that this may be caused by the bodys inflammatory response to the virus, said Avindra Nath, M.D., clinical director at the NIHs National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.

Although COVID-19 is primarily a respiratory disease, patients often experience neurological problems including headaches, delirium, cognitive dysfunction, dizziness, fatigue, and loss of the sense of smell. The disease may also cause patients to suffer strokes and other neuropathologies.

Several studies have shown that the disease can cause inflammation and blood vessel damage. In one of these studies, the researchers found evidence of small amounts of SARS-CoV-2 in some patients brains. Nevertheless, scientists are still trying to understand how the disease affects the brain.

In this study, the researchers conducted an in-depth examination of brain tissue samples from 19 patients who had died after experiencing COVID-19 between March and July 2020. Samples from 16 of the patients were provided by the Office of the Chief Medical Examiner in New York City while the other 3 cases were provided by the department of pathology at the University of Iowa College of Medicine, Iowa City. The patients died at a wide range of ages, from 5 to 73 years old. They died within a few hours to two months after reporting symptoms. Many patients had one or more risk factors, including diabetes, obesity, and cardiovascular disease. Eight of the patients were found dead at home or in public settings. Another three patients collapsed and died suddenly.

Initially, the researchers used a special, high-powered magnetic resonance imaging (MRI) scanner that is 4 to 10 times more sensitive than most MRI scanners, to examine samples of the olfactory bulbs and brainstems from each patient. These regions are thought to be highly susceptible to COVID-19. Olfactory bulbs control our sense of smell while the brainstem controls our breathing and heart rate. The scans revealed that both regions had an abundance of bright spots, called hyperintensities, that often indicate inflammation, and dark spots, called hypointensities, that represent bleeding.

The researchers then used the scans as a guide to examine the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaking blood proteins, like fibrinogen, into the brain. This appeared to trigger an immune reaction. The spots were surrounded by T cells from the blood and the brains own immune cells called microglia. In contrast, the dark spots contained both clotted and leaky blood vessels but no immune response.

We were completely surprised. Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases, said Dr. Nath.

Finally, the researchers saw no signs of infection in the brain tissue samples even though they used several methods for detecting genetic material or proteins from SARS-CoV-2.

So far, our results suggest that the damage we saw may not have been not caused by the SARS-CoV-2 virus directly infecting the brain, said Dr. Nath. In the future, we plan to study how COVID-19 harms the brains blood vessels and whether that produces some of the short- and long-term symptoms we see in patients.

This study was supported by NIH Intramural Research Program at the National Institute of Neurological Disorders and Stroke (NS003130) and an NIH grant (NS109284).

Reference: Lee, MH, et al. Microvascular Injury in the Brains of Patients with COVID-19. N Engl J Med. 2020. ePub 30 Dec. doi: 10.1056/NEJMc2033369.

About National Institute of Neurological Diseases and Stroke (NINDS): NINDS is the nations leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institute on Aging (NIA): NIA leads the U.S. federal government effort to conduct and support research on aging and the health and well-being of older people. Learn more about age-related cognitive change and neurodegenerative diseases via NIAs Alzheimer's and related Dementias Education and Referral (ADEAR) Center website. For information about a broad range of aging topics, visit the main NIA website and stay connected.

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

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NIH study uncovers blood vessel damage and inflammation in COVID-19 patients' brains but no infection - National Institute on Aging


30 Years Since the Human Genome Project Began, Whats Next? – WIRED

Saturday, January 2nd, 2021

In 1987, when researchers first used the word genomics to describe the newly developing discipline of mapping DNA, Eric Green had just finished medical school. A few years later, he found himself working on the front lines of the young fields marquee moon shot: the Human Genome Project. To lead the nations participation in the global effort, Congress established the National Human Genomics Research Institute, or NHGRI, in 1989.

Sequencing the entire human genome began the following year, and it took 13 years to complete. Not long after, in 2009, Green took the helm of the research institute. By then, NHGRIs mission had evolved to include expanding the field of genomics into medicine. That meant funding and coordinating projects aimed at pinpointing the mutations responsible for genetic disorders, then developing tests to diagnose them and therapies to treat them. And even more broadly, it meant generating evidence that DNA data could effectively improve outcomes, even for people who dont suffer from rare diseases.

To help chart that course, one of Greens tasks is to periodically put together a strategic vision for the field. Aimed at celebrating progress, identifying technological gaps, and inspiring scientists to pursue the most impactful areas of research, his team published its latest projection in October. For the first time, Green and his colleagues outlined a set of 10 bold predictions about what might be realized in human genomics by the year 2030. Among them: High schoolers will show off genetic analyses at the science fair, and genomic testing at the doctors office will become as routine as basic blood work.

Three decades after that sequencing race began, weve perhaps reached the end of the early genomics era, a period of explosive technological growth that led to breakthroughs like the sequencing of the first dog, chicken, and cancer cells and the advent of cheap home DNA tests. The field has matured to the point that genomics is nearly ubiquitous in all of biologyfrom fighting invasive giant hornets to brewing better-tasting beer. Genomic medicine is no longer theoretical. But its also not widespread. Although scientists have mapped the human genome, they do not yet completely understand it. Green spoke to WIRED about what the next decade, and the next era in genomics, may have in store. This interview has been edited for length and clarity.

WIRED: October marked the 30th anniversary of the Human Genome Project. When you look around at where we are today, how does it live up to the expectations you had for the impacts the project would make in medicine?

Eric Green: I was inside the Human Genome Project from day one, and I cant stress enough how back then we didnt know what we were doing. We had this big audacious goal of reading out the 3 billion letters of the human instruction book, but we didnt have the technology to do it. We didnt have the methods. We didnt even have a functional internet. There was no playbook. So, as someone who got into this as a young physician, I could sort of imagine that one day genomics might be part of clinical care. But I truly did not think it would happen in my lifetime.

If we go back just 10 years, nobody was really using genomics in health care. We fantasized then about the idea of having a patient in front of us, where we did not know what was wrong with them, and being able to sequence their genome and figure it out. That was a hypothetical in 2011. Now it's routine. At least for people suspected of having a rare genetic disease.

Thats amazing. But also, its still a far cry from some of the hype around what the Human Genome Project was going to accomplish. In his remarks at the White House in 2000, then-NHGRI director Francis Collins said it would likely take 15 or 20 years to see a complete transformation in therapeutic medicine, promising personalized treatments for everything from cancer to mental illness. Obviously, that hasnt exactly come to pass. Why not?

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30 Years Since the Human Genome Project Began, Whats Next? - WIRED


rBIO Launches with Technology to Hyper-Produce Insulin Cost-Effectively, at Scale – BioSpace

Saturday, January 2nd, 2021

rBIO launched last week with technology that can reduce the cost of insulin by 30 percent, making U.S. manufacturing cost-effective for insulin and several other drugs.

This new method is an enhancement of the recombinant DNA (rDNA) processes that have been used since the 1980s to produce insulin.

Forty years later, were taking it to the next level, Cameron Owen, rBIO co-founder and CEO, told BioSpace. It is akin to expediting billions of years of evolution.

The company genetically modified E. coli to cause it to hyper-produce peptide hormones initially, insulin thereby creating more product from the same quantity of material. Those bacteria will then manufacture the product at scale using standard vat fermentation processes.

The idea emerged when Owen was a graduate student at Johns Hopkins Universitys Carey Business School.

I had started another biotech company (Aevus Precision Diagnostics) that looked at the pharmacogenomics of diabetes medications, so I got to know the diabetes space really well, he said.

As he learned, Insulin is too expensive for many people who depend on it, and its supply chain is vulnerable because like most drugs used in the U.S. a large percentage of insulin is manufactured offshore. With 30 million diabetics in the U.S. now, and an expected 60 million by 2030, keeping up with demand is a significant challenge.

In 2016, the J. Craig Venter Institute determined the minimum number of genes bacteria needed to survive.

If you can take those minimal genes and add to them, youve eliminated a lot of processing waste, Owen said.

Therefore, rBIO is rewriting E.colis genetic code, eliminating the unnecessary genes and coding the genome so the bacteria hyper-expresses the maximum quantities of insulin but does not produce the products needed for the bacterias normal metabolic function.

rBIOs goal is to increase production to the cells theoretical limits. In this case, thats 100 molecules of insulin.

We havent achieved 100% theoretical maximum yield, he said, but production rates are approximately double that of todays generally accepted insulin production methods.

Whats different about this approach, beyond its high yield, is how the genetic code as devised. Were now at the point in genetics where the genetic code can be not only manipulated, but written, Owen said.

Rather than cut and paste genes in or out of organisms, rBIO actually designs the DNA, he said.

Were writing the DNA code from scratch, the way a computer programmer would, and translate it to biology, he said. Rather than use ones and zeros, we use ACGT the bases found in DNA molecules. We can manipulate those letters to write anything you want.

The rBIO team doesnt start entirely from scratch, of course. There are set sequences that we know work, so we are using those sequences, and designing others, Owen said. We wrote three different genetic codes for the bacteria during the past several months and put them into a lab setting to determine if they first and foremost grew and divided, and secondly whether they produced the product we wanted.

Two of the three bacteria strains were successful, and optimization is continuing.

Once rBIO determines the genetic code it wants, it outsources the actual gene assembly. rBIO has produced several milligrams of insulin this way in the lab.

The next stage, Owen said, is to scale up the company. That means bringing in management with the skills to take the organization to the next level and to help shape its direction.

This early in its existence, all the options are open.

My goal is to become a manufacturer, Owen said, but, realistically, this is more of an out-licensing opportunity to a company with the existing infrastructure for mass manufacturing already in place.

rBIO is still developing a platform technology, Owen pointed out. The company is focused on insulin, but also is considering eight other drugs for its pipeline, including erythropoietin and epinephrine. They each have a projected compound annual growth rate (CAGR) of 12 percent for the next decade, he said, so represent significant opportunities for the company.

Owen said the companys technology also has the potential to make reshoring attractive for several drugs that currently are produced offshore.

The COVID-19 pandemic put the spotlight on the risks of off-shoring pharmaceutical products. According to the FDA, only 21% of the drugs on the World Health Organizations Essential Medicines List are manufactured in the U.S.

Medicine security shouldnt be allowed to be affected by the fluctuations of international trade policies, he said. Having the manufacture of life-saving medicines offshore is a major national security issue. Imagine what would happen if 30 million American diabetics couldnt access insulin. Wed be in a world of hurt.

Whether or not such drastic trade wars happen, rBIOs hyperproduction technology may offer significant benefits to therapeutic manufacturers and customers alike. He isnt overly concerned about competition. Instead, he sees potential allies.

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rBIO Launches with Technology to Hyper-Produce Insulin Cost-Effectively, at Scale - BioSpace


Effects of Peer Victimization on Child and Adolescent Physical Health – American Academy of Pediatrics

Saturday, January 2nd, 2021

Peer victimization is recognized as a pressing public health issue, affecting 1 in 5 youth. Although extensive research demonstrates the negative effects of peer victimization on youth mental health, considerably less is known about if and how peer victimization adversely impacts physical health. Focusing on studies published in the past 5 years, this state-of-the-art review synthesizes recent research examining the relationship between peer victimization and physical health outcomes among children and adolescents. In addition to reviewing evidence for associations between peer victimization and global subjective health indices (eg, somatic symptoms), I highlight several biological sequelae of victimization (eg, cortisol dysregulation, inflammation) that may increase long-term risk for illness and disease. I conclude by considering strengths and limitations of existing work and suggesting several key directions for future research. I also discuss implications for practitioners and the role primary care providers can play in promoting health among peer victimized youth.

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Effects of Peer Victimization on Child and Adolescent Physical Health - American Academy of Pediatrics


Lynparza approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers – India Education Diary

Saturday, January 2nd, 2021

AstraZeneca and MSDs Lynparza (olaparib) has been approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers.

The three approvals authorise Lynparza for: maintenance treatment after 1st-line chemotherapy containing bevacizumab (genetical recombination) for patients with homologous recombination repair deficient (HRD) ovarian cancer; the treatment of patients with BRCA gene-mutated (BRCAm) castrate-resistant prostate cancer with distant metastasis (mCRPC); and as maintenance treatment after platinum-based chemotherapy for patients with BRCAm curatively unresectable pancreas cancer.

The concurrent approvals by the Japanese Ministry of Health, Labour, and Welfare are based on positive results from the PAOLA-1, PROfound and POLO Phase III trials, which each were published in The New England Journal of Medicine.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: These three approvals allow patients in Japan to be treated with Lynparza, a targeted treatment personalised to their specific biomarkers. They further underline the critical importance of biomarker testing at diagnosis, which helps physicians determine a course of treatment tailored to individual patients to substantially delay disease progression.

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: For patients in Japan diagnosed with each of these types of cancer there are very few treatment options. Approvals for treatments such as Lynparza, the first PARP inhibitor to be approved in these specific types of metastatic castration-resistant prostate cancer and metastatic pancreatic cancer in Japan, enable us to advance this evolving era of personalised medicine and change how these cancers are treated.

Lynparza in ovarian cancerThe approval as 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer is based on a biomarker subgroup analysis of the PAOLA-1 Phase III trial which showed Lynparza, in combination with bevacizumab maintenance treatment, demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone, for patients with HRD-positive advanced ovarian cancer.

In 2020, nearly 11,000 women in Japan were diagnosed with ovarian cancer, with more than 5,000 women dying of the disease.1 One in two women with advanced ovarian cancer has an HRD-positive tumour.2,3

Lynparza in prostate cancerThe approval for the treatment of BRCAm mCRPC is based on a subgroup analysis of the PROfound Phase III trial which showed Lynparza demonstrated a substantial improvement in radiographic progression-free survival (rPFS) and overall survival (OS) versus enzalutamide or abiraterone in men with BRCA1/2 mutations. Lynparza is the first and only PARP inhibitor approved in Japan in advanced prostate cancer.

Prostate cancer is the third most common type of cancer in Japan and in 2020, accounted for over 100,000 new cases.1 With limited treatment options, the average survival for men with mCRPC is only 9-13 months.8 Approximately 12% of men with mCRPC have a BRCA mutation,5 a subgroup of patients with a particularly poor prognosis.

Lynparza in pancreatic cancerThe approval for BRCAm metastatic pancreatic cancer is based on the results of the POLO Phase III trial which showed Lynparza demonstrated a statistically significant and clinically meaningful improvement in PFS versus placebo in patients with germline BRCAm metastatic pancreatic cancer. Lynparza is the first and only PARP inhibitor approved in this disease.

Pancreatic cancer has one of the lowest survival rates of the most common cancers and in Japan was responsible for almost 40,000 deaths in 2020 the fourth most common cause of cancer death.1,5 Japan has the third-highest rate of pancreatic cancer in the world with 44,000 new cases diagnosed in 2020.1,6 Approximately 5-7% of patients with metastatic pancreatic cancer have a germline BRCA mutation.7

AstraZeneca and MSD are exploring additional trials in advanced prostate cancer including the ongoing PROpel Phase III trial testing Lynparza as a 1st-line treatment for patients with mCRPC in combination with abiraterone versus abiraterone alone. Data are anticipated in the second half of 2021. AstraZeneca is exploring additional trials in advanced ovarian cancer, including the DUO-O Phase III trial testing Imfinzi (durvalumab) in combination with chemotherapy and bevacizumab, followed by maintenance treatment with Imfinzi, bevacizumab, and Lynparza in newly diagnosed advanced ovarian cancer patients.

PAOLA-1PAOLA-1 is a double-blinded Phase III trial testing the efficacy and safety ofLynparzaadded to standard-of-care bevacizumab versus bevacizumab alone, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. AstraZeneca and MSD announced in August 2019 that the trial met its primary endpoint of PFS in the overall trial population.

The PAOLA-1 Phase III trial showed that Lynparza, in combination with bevacizumab maintenance treatment, reduced the risk of disease progression or death by 67% (based on a hazard ratio [HR] of 0.33, 95% confidence interval [CI] 0.25-0.45). The addition of Lynparza improved PFS to a median of 37.2 months versus 17.7 with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.

PROfoundPROfound is a prospective, multicentre, randomised, open-label, Phase III trial testing the efficacy and safety of Lynparza versus enzalutamide or abiraterone in patients with mCRPC who have progressed on prior treatment that included new hormonal agents (abiraterone or enzalutamide) and have a qualifying tumour mutation in BRCA1/2, ATM or one of 12 other genes involved in the homologous recombination repair (HRR) pathway.

The trial was designed to analyse patients with HRR gene mutations in two cohorts: the primary endpoint was rPFS in those with mutations in BRCA1/2 or ATM genes and then, if Lynparza showed clinical benefit, a formal analysis was performed of the overall trial population of patients with HRR gene mutations (BRCA1/2, ATM, CDK12 and 11 other HRR gene mutations). AstraZeneca and MSD announced in August 2019 that the trial met its primary endpoint of rPFS.

The subgroup analysis from the PROfound Phase III trial showed Lynparza reduced the risk of disease progression or death by 78% (based on a HR of 0.22, 95% CI, 0.15-0.32; nominal p<0.0001) and improved rPFS to a median of 9.8 months versus 3.0 with enzalutamide or abiraterone in men with mCRPC with BRCA1/2 mutations. Lynparza reduced the risk of death by 37% (based on a HR of 0.63, 95% CI 0.42-0.95) with median OS of 20.1 months versus 14.4 with enzalutamide or abiraterone.

POLOPOLO is a randomised, double-blinded, placebo-controlled, multi-centre Phase III trial of Lynparza tablets (300mg twice daily) as maintenance monotherapy versus placebo. The trial randomised 154 patients with germline BRCAm metastatic pancreatic cancer whose disease had not progressed on 1st-line platinum-based chemotherapy. Patients were randomised (3:2) to receive Lynparza or placebo until disease progression. The primary endpoint was PFS and key secondary endpoints included OS, time to second disease progression, overall response rate and health-related quality of life.

Data from the Phase III POLO trial showed Lynparza nearly doubled the time patients with germline BRCAm metastatic pancreatic cancer lived without disease progression or death to a median of 7.4 months versus 3.8 on placebo and reduced the risk of disease progression or death by 47% (based on a HR of 0.53, 95% CI 0.35-0.82; p=0.004).

BRCABRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes are mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including Lynparza.8-11

HRDHRD, which defines a subgroup of ovarian cancer, encompasses a wide range of genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene mutations, HRD interferes with normal cell DNA repair mechanisms and confers sensitivity to PARP inhibitors including Lynparza.12

LynparzaLynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in HRR, such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in the US and EU as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability). Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US, the EU and several other countries for the treatment of germline BRCAm metastatic pancreatic cancer. Lynparza is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm and other HRR gene mutations) and in the EU for BRCAm metastatic castration-resistant prostate cancer. Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 40,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZenecas industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

The AstraZeneca and MSD strategic oncology collaborationIn July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the worlds first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncologyAstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients lives and the Companys future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of six scientific platforms Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

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Lynparza approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers - India Education Diary


The expanding role of genomics in preconceptional ‘personalised’ medicine – ESHRE

Saturday, December 26th, 2020

A well attended online Campus course staged by the SIG Reproductive Genetics heard that the expansion of sequencing analysis is poised to push forward the development of cost-effective preconception tests able to identify several underlying genetic causes of infertility

The everyday implications of preconceptional medicine have so far been largely evident in lifestyle advice conducive to successful pregnancy, but a well attended online Campus meeting staged in December suggests that genomic medicine has an increasingly important role to play. Sessions at the meeting not only covered the much debated subject of genetic risk assessment by expanded carrier screening, but explored the application of genome-wide sequencing in recurrent miscarriage, in predicting ART outcomes from parental genome analysis, and even in explaining the different responses to ovarian stimulation with gonadotrophins. Such subjects, especially expanded carrier screening, are not without their ethical problems, notably in the disclosure (or not) of secondary findings, so it was also appropriate at this meeting to hear a preview of ESHREs forthcoming recommendations on expanded carrier screening in ART.

In his opening lecture Stphane Viville, a former coordinator of ESHREs SIG Reproductive Genetics, said that known genetic and chromosomal factors account for around 20% of all infertility cases, with three additional (and relatively unknown) phenotypes now moving into active research: POI, oocyte maturation defect, and preimplantation embryonic lethality, all of which were covered at this meeting. Viville added that so far at least 21 genes have been implicated in POI and advised that genetics is now getting more and more into IVF labs and no longer confined to chromosomal aberrations or microdeletions on the Y chromosome.

Much of the content of this Campus course has been explored in detail in a recent Human Reproduction Update review, whose first author, Antonio Capalbo, is deputy of ESHREs SIG Reproductive Genetics and an organiser of this course.(1) In the review, as was repeatedly implied at this meeting, Capalbo et al note that the expansion of sequencing analysis may enable the development of cost-effective preconception tests capable of identifying underlying genetic causes of infertility, which until now have largely been defined as idiopathic.

One such step in this move towards a more positive and personalised approach to preconceptional medicine is in genetic risk assessment by expanded carrier screening, which occupied a large section of this meeting. James Goldberg, prominent in the development of ECS, said its availability now steps beyond the disparities and restrictions of ethnicity-specific screening and aims to inform couples about their risk of having children with autosomal recessive and X-linked recessive disorders and thereby to support informed decision making. Nevertheless, two of the current guidance statements on ECS cited by Goldberg both from the USA are largely based on ethnicity screening with an emphasis on cystic fibrosis and spinal muscular dystrophy. ECS, said Goldberg, represents a more equitable approach to identifying risk. Such risk assessment in both the general population and IVF couples - will allow identification of those who carry recessive mutations, and thereby provide increased reproductive autonomy to couples deemed at risk and where PGT is available for embryo selection.

However, when a publicly provided ECS programme was set up in Amsterdam offering a test panel of 50 genes (at a cost of 650 euro per test) and following the guidance of the European Society of Human Genetics, there was a relatively quiet response (20%) from the general risk population, and higher (80%) from the high risk population.(2) Nevertheless, assessment of the programme, began in 2016, appeared to raise more questions than answers, and no clear resolution of how such a programme might be best provided. Capalbo and his fellow Update reviewers concluded that ECS represents one of the most effective and advanced applications of preconception genomic medicine worldwide today and is expected to grow in application in coming years.

The preview of recommendations from ESHREs Ethics Committee was specifically about ECS ahead of ART (and not just involving gamete donors). Thus, asked Dutch bioethicist Guido de Wert, would the offer of ECS to all such applicants be proportionate, and if so, for what kinds of disorders and under what conditions? Applying the three ethicists principles of proportionality, respect for autonomy and justice, De Wert firstly noted that any possible benefits should clearly outweigh any possible harms, that ECS should still be embedded in a research framework, and that a couples access to ECS should only be on condition that they take preventive measures and apply for PGT, donor gametes, or, maybe, prenatal diagnosis.

Even the outcome of fertility treatments may well be affected by genetic mutations, and such extreme outcomes as oocyte maturation failure and embryonic developmental arrest are now investigated as a genetic cause of infertility. Indeed, Semra Kahraman from theIstanbul Memorial Hospital reported that variants in more than 2000 genes are now predicted to be involved in various infertility pathways. She described her own study in which 22 IVF patients whose repeated failure was attributed to oocyte maturation failure and embryo development arrest and who were investigated using whole exome sequencing panels. Family history analysis had also identified infertility and early menopause in the family of nine of the subjects. The analysis identified genomic variants in eight of the 22 subjects, including four genes known to be lethal at the embryonic stage.

With ovarian ageing identified as one of todays most frequent causes of infertility, John Berry, an MRC investigator from Cambridge, reported in a keynote lecture that ten years ago population studies had identified four common genetic variants associated with menopause. Today, he added, there are now more than 300 loci identified, which explain around 10% of the heritable component. Too few to be clinically useful? he asked. Again, there appeared more questions than answers, notably if POI can be explained solely by monogenic alleles and if menopausal age can indeed be predicted by genetics.

The conclusions from this meeting, as well as the increasing number of genes and variants identified, suggest that genomic assessment ahead of conception may have real clinical benefits at both the individual (in identifying genetic risks in the male and female partner) and the couple level (in allowing a specific reproductive prognosis). Information at this early stage may thus lay the basis for personalised interventions, and certainly make at-risk couples better informed of their reproductive choices.

1. Capalbo A, Poli M, Riera-Escamilla A, et al. Preconception genome medicine: current state and future perspectives to improve infertility diagnosis and reproductive and health outcomes based on individual genomic data, Hum Reprod Update 2020; doi:10.1093/humupd/dmaa044

2. Henneman L, Borry P, Chokoshvili D, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet 2016; 24: e1-e12. doi:10.1038/ejhg.2015.27

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The expanding role of genomics in preconceptional 'personalised' medicine - ESHRE


Digbi Health partners with West Virginia University Medicine and WVU Bariatrics Surgical Weight-Loss Program to improve postoperative weight loss…

Saturday, December 26th, 2020

This clinical pilot will evaluate the effectiveness of Digbi Health's obesity management digital program personalized to each bariatric surgery patient, one-year post sleeve gastrectomy, based on their lifestyle, genetic and gut microbiome risks, in further reducing weight and maintaining weight loss. Obesity is a complex metabolic disease and an ongoing epidemic, with associated inflammatory, digestive, musculoskeletal, skin morbidities, as well as a risk factor for diabetes, cardiovascular disease, COVID-19, and reduced life expectancy, which currently affects 42 percent of the adult population in the United States. Bariatric surgery is the most effective long term intervention for morbid obesity, and successful bariatric surgery outcomes depend on lifelong changes in eating patterns and social support.

Research indicates individuals' genetic and gut microbiome makeups are intrinsically linked to their metabolism and following personalized nutrition recommendations and meal plans curated to an individual's genetic and gut microbiome markers may assist with further weight loss and ongoing weight maintenance post sleeve gastrectomy.

"WVU Bariatrics is excited to partner with Digbi Health to better understand how genomic, gut microbiome and metabolomic factors can contribute to successful weight loss following bariatric surgery," said Nova Szoka MD, FACS, FASMBS, Assistant Professor at J.W. Ruby Memorial Hospital, WVU Bariatrics Surgical Weight-Loss Center and principal investigator of the study.

"Digbi Health is the first company to operationalize a genetic and gut microbiome-based prescription-grade platform for doctors and payers to deliver weight loss, digestive health, and diabetes care programs at scale," said Ranjan Sinha, CEO, and founder of Digbi Health.

"Digbi is committed to empowering people suffering from obesity and chronic inflammatory lifestyle illnesses, struggling with ineffective one-size-fits-all diets, with personalized nutrition and lifestyle support that works for them. Through this collaboration with WVU Medical, we aim to deeper explore the critical importance of personalized nutrition and its direct impact on people suffering from obesity and associated illnesses," said Sinha.

More information about J.W. Ruby Memorial Hospital, WVU Medical, and Surgical Weight-Loss Center can be found here.

About Digbi HealthDigbi Healthis a first-of-its-kind precision digital therapeutics company that offers a prescription-grade digitally enabled personalized obesity and obesity-related gut, skin disorders, hypertension, and other cardiometabolic health management programs based on an individual's gut biome, genetic risks, blood markers, and lifestyle factors. Digbi Health and members of its physician network are committed to empowering people to take control of their own health and wellness. Digbi Health is prescribed by doctors, healthcare providers, and insurance companies.

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Audentes Therapeutics Announces FDA Lifts Hold on ASPIRO Clinical Trial of AT132 for Treatment of X-Linked Myotubular Myopathy (XLMTM) – BioSpace

Saturday, December 26th, 2020

Dec. 24, 2020 23:30 UTC

SAN FRANCISCO--(BUSINESS WIRE)-- Audentes Therapeutics, an Astellas genetic medicines company, today announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold for the ASPIRO clinical trial evaluating AT132 in patients with X-linked myotubular myopathy (XLMTM). XLMTM is a serious, life-threatening neuromuscular disease characterized by extreme muscle weakness, respiratory failure, and early death.

We are grateful for the efforts of our team and investigators who have worked tirelessly to answer the FDAs questions and we now look forward to resuming this study, said Natalie Holles, President and Chief Executive Officer of Audentes. We want to again extend our deepest sympathies to patients families impacted by the events earlier this year. We are deeply committed to the continued safe development of AT132 for the families and patients living with XLMTM, a disease with no existing treatments.

The company is now working to complete all clinical and regulatory activities necessary to resume dosing and plans to have discussions at a future date with the regulators on the path forward toward global registration filings for AT132.

About X-linked Myotubular Myopathy XLMTM is a serious, life-threatening, rare neuromuscular disease that is characterized by extreme muscle weakness, respiratory failure and early death. Mortality rates are estimated to be 50 percent in the first 18 months of life. For those patients who survive past infancy, there is an estimated additional 25 percent mortality by the age of 10. XLMTM is caused by mutations in the MTM1 gene that lead to a lack or dysfunction of myotubularin, a protein that is needed for normal development, maturation and function of skeletal muscle cells. The disease affects approximately 1 in 40,000 to 50,000 newborn males.

XLMTM places a substantial burden of care on patients, families and the healthcare system, including high rates of healthcare utilization, hospitalization and surgical intervention. More than 80 percent of XLMTM patients require ventilator support, and the majority of patients require a gastrostomy tube for nutritional support. In most patients, normal developmental motor milestones are delayed or never achieved. Currently, only supportive treatment options, such as ventilator use or a feeding tube, are available.

About the ASPIRO Study ASPIRO is a two-part, multinational, randomized, open-label ascending dose trial to evaluate the safety and preliminary efficacy of AT132 in XLMTM patients less than five years of age. Primary endpoints include safety (adverse events and certain laboratory measures) and efficacy (assessments of neuromuscular and respiratory function). Secondary endpoints include the burden of disease and health-related quality-of-life, and muscle tissue histology and biomarkers.

About AT132 for the treatment of X-linked Myotubular Myopathy Audentes is developing AT132, an AAV8 vector containing a functional copy of the MTM1 gene, for the treatment of XLMTM. AT132 may provide patients with significantly improved outcomes based on the ability of AAV8 to target skeletal muscle and increase myotubularin expression in targeted tissues following a single intravenous administration. The preclinical development of AT132 was conducted in collaboration with Genethon (

AT132 has been granted Regenerative Medicine and Advanced Therapy (RMAT), Rare Pediatric Disease, Fast Track, and Orphan Drug designations by the U.S. Food and Drug Administration (FDA), and Priority Medicines (PRIME) and Orphan Drug designations by the European Medicines Agency (EMA).

About Audentes Therapeutics, Inc. Audentes Therapeutics, an Astellas company, is developing genetic medicines with the potential to deliver transformative value for patients. Based on our innovative scientific approach and industry leading internal manufacturing capability and expertise, we have become the Astellas Center of Excellence for the newly created Genetic Regulation Focus Area. We are currently exploring three gene therapy modalities: gene replacement, exon skipping gene therapy, and vectorized RNA knockdown, with plans to expand our focus and geographic reach under Astellas. We are based in San Francisco, with manufacturing and laboratory facilities in South San Francisco and Sanford, North Carolina.

About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+ healthcare solutions combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at

Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on managements current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas intellectual property rights by third parties.

Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

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Audentes Therapeutics Announces FDA Lifts Hold on ASPIRO Clinical Trial of AT132 for Treatment of X-Linked Myotubular Myopathy (XLMTM) - BioSpace


Hope on Hold: Promising Hemophilia B Therapy Paused by FDA – BioSpace

Saturday, December 26th, 2020

Even the most promising drugs can hit a pothole in the road to U.S. Food and Drug Administration (FDA) approval, particularly when working in the complicated, evolving world of gene therapies.

After touting positive Phase III resultsat ASH (American Society of Hematologys annual meeting),uniQuregot slapped with anFDA clinical holdfor their hemophilia B treatment due to a patient developing liver cancer.

Theresearch team alerted the FDA of the development after a lesion was found during a routine one-yearfollow-up.A hepatocellular carcinoma (HCC) isexpectedto be confirmed with a full surgical resection.

However, the cancer may not be related to the gene therapy, as this particular patient was high risk for liver cancerwith a long history of hepatitis C, hepatitis B virus, findings of non-alcoholic fatty liver disease and advanced age.UniQurepointed out thatchronicinfections with hep B and C are associated with 80% of HCC cases.

Patient safety will always be our top priority, and we are working closely with the FDA and our advisors to conduct a thorough investigation into the cause of this event which we expect to be completed in early 2021, said RicardoDolmetsch, Ph.D., president of R&D atuniQure. We will investigate whether there is a relationship to treatment. At this time, we do not have adequate data to determine a possible causal relationship, especially in the context of the other known risk factors.

The hold is not expected to affect the pivotal trial results as the dosing of the patients is completed.

While several treatments areavailable for hemophilia B, doctors and patients are holding out hope for a cure that will stop the disease at its source. Thats thepotential that genetic medicine has held for this area.

UniQuresdrug, AMT-061, substantially increased production of the blood-clotting protein factor IX, thefactor missing forhemophiliaBpatients,innearly all trial participants with moderate to severe disease.

Drug developers have run into a challenge with gene therapies in patients with high levels of neutralizing antibodies. Those antibodies can disarma gene therapyby attacking its viral vector delivery systembefore it ever has the chance to help thepatient.Many gene therapy trials wont enroll patients who test positive for neutralizing antibodies.

UniQuresgene therapy is delivered by an AAV5 vehicle, whichis believed to be harder to impair than other vectors.The company enrolled 23 patients with neutralizing antibodiespresent.Only one patient did not respondto the therapy. That was one who had a large amount of theantibodies- encouraging results that at least some with neutralizing antibodies could go on the therapy.

All patients in our hemophilia B gene therapy program, including the 54 patients in HOPE-B, will continue to be monitored by their care teams while we gather additional information as rapidly as possible, noted CEO Matt Kapusta. We do not anticipate any impact to our regulatory submission timeline for the hemophilia B program as a result of this clinical hold.

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Hope on Hold: Promising Hemophilia B Therapy Paused by FDA - BioSpace


WVU Medicine Children’s Dr. Mary Louise Russell brings 30-plus years experience in the treatment of children with movement issues – WV News

Saturday, December 26th, 2020

MORGANTOWN, W.Va. (WV News) Dr. Mary Louise Russell is a member of the team of experts at the WVU Medicine Childrens that specializes in pediatric physical medicine and rehabilitation.

She and her colleagues treat children who have movement issues due to a wide range of causes, Russell said.

Sometimes the children only have movement problems, and sometimes the movement problems are part of a more complex picture, she said. For example, children with Down syndrome can have movement problems, and they might be behind on learning to walk. But, they might have other problems, too, like developmental delay and even some other medical difficulties, like heart defects or GI problems.

She sees children of all ages, from just nine days old to beyond age 18, Russell said.

For new patients, well go all the way to 18 years. Although, for some who have had pediatric onset of chronic conditions, well see them into at least young adulthood, say mid-20s, she said. That would usually be a person with cerebral palsy.

Cerebral palsy is among the most common diagnosis she sees, Russell said.

Cerebral palsy is a problem with how the brain works that effects how somebody moves. It can be confined to the movement control part of the brain, or there may be other problems, like seizures or developmental delay, she said.

There are a variety of treatments for patients with cerebral palsy, Russell said.

The first treatment to be used is physical and occupational therapy, she said. In the United States, there is a service called Birth to Three or Early Intervention that is a federal government-supported service administered by states for kids to get in-home therapy services.

Other treatments for cerebral palsy include braces, walkers, crutches, or wheelchairs, Russell said.

Medications can be administered to reduce tone spasticity, and orthopaedic or neurosurgery can help to reduce muscle spasticity, she said. There is a variety of possible treatments that cover a range of issues.

The COVID-19 pandemic has forced her to rely on remote visits with some patients, which isnt quite the same as seeing them in person, Russell said.

I think its better than nothing, but for what I do say for a patient with cerebral palsy I really like to be able to feel how much resistance they give me when trying to stretch their arms or their legs, she said. Thats kind of a hard thing to do from a screen.

She looks forward to being able to see all of her patients in-person again in the near future, Russell said.

A lot of families right now are reluctant to bring their children for in-person visits, and I can understand. Many of these kids are medically fragile or chronically ill, she said. We just need to wait a little while longer for their in-person visits.

Russell, who has more than 30 years of medical experience, said she has seen significant leaps in what genetics can reveal about a patients condition.

What has been the biggest help to us has been advances in genetics, she said. I can remember when we would just diagnose them and say They have low muscle tone. Now, were able to identify genetic syndromes and where parts of a chromosome may be missing or duplicated.

When she was first starting out information was much more limited, Russell said.

Having genetic information helps you with set reasonable goals, she said. You may not be able to fix the underlying problem, but you know what to expect and to plan for.

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WVU Medicine Children's Dr. Mary Louise Russell brings 30-plus years experience in the treatment of children with movement issues - WV News


The latest on the coronavirus pandemic and vaccines: Live updates – CNN

Saturday, December 26th, 2020

Dozens of countries have banned travel from the UK in an effort to contain a new Covid-19 variant first reported in England.

The new mutation is being called VUI-202012/01 the first "Variant Under Investigation" in the UK in December 2020. While scientists hunt for more information about the variant, its impact is already being felt, with dozens of countriesimposing restrictions on travelers from the UK.

Here's what we know so far about the Covid-19 variant:

What is a variant and why are officials concerned about this one?A variant occurs when the genetic structure of a virus changes. All viruses mutate over time and new variants are common, including for the novel coronavirus.

Like other variants, this one carries agenetic fingerprint that makes it easy to track, and it happens to be one that is now widespread in southeast England. That alone does not necessarily mean a variant is more contagious or dangerous.

But scientists advising the UK government have estimated that this variant could be up to 70% more effective at spreading than others. Peter Horby, chair of theNew and Emerging Respiratory Virus Threats Advisory Group(NERVTAG), said Monday that experts "now have high confidence that this variant does have a transmission advantage" over other variants.

The World Health Organization said Tuesday that the changes to the variant include 14 key mutations, and that some of them "may influence the transmissibility of the virus in humans," though it added that further laboratory investigations were needed.

Where did the variant originate and how has it taken hold?The new variant is believed to have originated in southeast England, according to the WHO. Public Health England (PHE) says backwards tracing, using genetic evidence, suggests the variant first emerged in England in September. It then circulated in very low levels until mid-November.

Chris Whitty, England's chief medical officer, said Saturday the variant was responsible for 60% of new infections in London, which have nearly doubled in the last week alone.

Multiple experts have also suggested that this new variant could have been amplified because of a superspreader event, meaning the current spike in cases could also have been caused by human behavior.

Is the new variant more deadly? There is no evidence as of now to suggest that the new variant is more deadly, according to Whitty and the WHO, though it is too early to tell.

Several experts have noted that in some cases, virus mutations that increase transmissibility are accompanied by a drop in virulence and mortality rates.

"As viruses are transmitted, those that allow for increased virological 'success' can be selected for, which changes the properties of the virus over time. This typically leads to more transmission and less virulence," Martin Hibberd, professor of emerging infectious disease at the London School of Hygiene & Tropical Medicine, told the SMC.

Learn more about the UK coronavirus varianthere.

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The latest on the coronavirus pandemic and vaccines: Live updates - CNN


Should Pregnant and Breastfeeding Patients Get the COVID-19 Vaccine? – University of Michigan Health System News

Saturday, December 26th, 2020

As the COVID-19 vaccine starts rolling out across the country, pregnant or breastfeeding women may be wondering if they should get it too.

First, the unknowns: Because clinical trials didnt include pregnant patients, there is no conclusive evidence related to vaccine safety and efficacy during pregnancy.

What experts do know: Pregnant patients are at higher risk of severe disease and worse outcomes from COVID-19 than non-pregnant peers and therefore would benefit from protection from the virus.

We have been following the research and federal guidance closely about pregnancy and the COVID-19 vaccine, says Molly Stout, M.D., MSCI, maternal fetal medicine director at Michigan Medicine Von Voigtlander Womens Hospital.

Based on the current information available and known risks of COVID-19 severity in pregnancy, we strongly recommend that pregnant and nursing people have access to the vaccine. We advise patients to discuss potential benefits and unknown risks specific to their individual situation with their healthcare provider.

Stout responds to some of the top questions about the COVID-19 vaccine and pregnancy:

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Stout: No, the vaccines have not been studied in pregnancy specifically. A few unexpected pregnancies occurred during the vaccine trials in participants, but we dont have further data on those cases at this time. There are ongoing efforts to include pregnant women in current COVID-19 vaccine trials.

Stout: Because pregnant women were not included in the early studies, we cannot be certain of how well the vaccine will work in pregnancy. The vaccine appears to be 95% effective in reducing COVID-19 disease in non-pregnant individuals. We also do not have specific safety information in pregnancy. However, the consensus of scientists, doctors, and professional organizations in the U.S. is to support pregnant women receiving the vaccine because the health risks of COVID-19 in pregnancy can be severe.

This recommendation is based on the known risk of COVID-19 in pregnancy and the biology of mRNA vaccines which are made with a string of the virus genetic material (a message of RNA that generates protein) and not the virus itself.

The technology of mRNA vaccines has been available for a long time and in general the risks from this form of vaccine are low. Also, the safety profile of the vaccine from the randomized control trials in non-pregnant individuals suggested no significant safety concerns.

Stout: Its important to understand that there is no way to get COVID-19 from the vaccine. While some vaccines are called live because they contain the virus, the COVID-19 vaccine is not one of them. However, when your immune system is doing its job reacting to the vaccine, you may experience some flu-like symptoms.

Eighty-four percent of people in the studies experienced redness or soreness at the site of the injection, over half felt fatigue and a headache, 1/3 had muscle pain and chills and 15-20% had joint pain or a fever.

Scientists think these symptoms are related to the vaccine activating your immune system to make the cells and proteins against COVID-19. There havent been any dangerous safety events that occurred more commonly in people who got the vaccine.

Stout: Vaccination is recommended for nursing mothers because benefits of the vaccine outweigh the theoretical risks regarding the safety of vaccinating.

Vaccine trials excluded lactating individuals, so we dont have any clinical data on the safety of the vaccine during lactation. However, because of the biology of the vaccine, (which doesnt involve a live virus) there should be no transfer into breastmilk.

In fact, antibodies from the lactating mother that transfer into the breastmilk may actually protect the breastfeeding child. The Academy of Breastfeeding Medicine does not recommend stopping breastfeeding for people who get the COVID-19 vaccine.

Stout: We have seen some misinformation about this topic. It is too early to know whether the vaccine has any impact on fertility, but we dont suspect it does.

The mRNA vaccines do not incorporate into the genetic material of the individual. The mRNA is the code or message to make a protein that helps the body react more quickly if exposed to COVID-19. Thus, there is no genetic reason an egg or a sperm would be affected by the vaccine.

A pregnancy test prior to vaccination isnt recommended or required.

Stout: Because of their higher risk of exposure, certain groups have been prioritized for initial vaccine distribution, including healthcare workers, first responders and workers in long-term healthcare facilities.

The general guidance is that pregnant patients who are in these frontline categories should be able to receive the vaccine as soon as they meet the criteria and its available to them.

Stout: Right now there havent been any recommendations to change dosing or schedules for the COVID-19 vaccine for people with allergies who experience anaphylaxis.

Stout: Recent studies have suggested that pregnant people who contract COVID-19 have a higher risk of severe illness and outcomes, such as being admitted to intensive care, being put on a ventilator and dying than non-pregnant women with the virus. These risks are higher for women of color, including African-American and Hispanic populations.

Adverse pregnancy outcomes such as preterm birth for COVID-positive patients have also been reported, but data in this area are still evolving.

Given these risks, pregnant patients should consider getting vaccinated against the virus and also take all other precautions to protect themselves from exposure by socially distancing, wearing masks and following safety guidelines.

Stout: Studies are limited in this area as well. There have been cases of newborns testing positive for COVID-19 shortly after birth. Whats unclear is whether they were infected with the virus before, during, or after birth from close contact with someone who had the virus.

Most newborns who tested positive for COVID-19 had mild or no symptoms.

Stout: The vaccine has been shown to decrease your chance of having COVID-19 symptoms and severe disease. What is unknown is whether vaccinated people can still carry and transmit the virus. For this reason, the recommendation is to continue to wear masks, socially distance and maintain other recommended safety measures even for people who have been vaccinated.

Stout: There have been efforts to collect outcomes data on pregnant women who have received the vaccine and our hope is that vaccine manufacturers report this information as it becomes available.

Development of the COVID-19 vaccine is a major scientific feat and marks the fastest vaccine development and distribution to date. Doctors and scientists agree COVID-19 vaccines will be a critical measure in slowing the spread and mortality associated with COVID-19. The downside of this remarkable scientific success is we have to be able to continue to collect longer term data as we follow pregnant and non-pregnant patients forward in time and continue to track vaccine success.

Stout: Based on what we know about how COVID-19 may negatively impact a pregnant patients health, we see great benefits to patients being protected from the virus through all measures available, including the vaccine.

We expect recommendations to continue to evolve as more data are collected about these vaccines and their use in specific populations, including pregnant patients. We will be following this evolving data closely and keeping all obstetric care providers at Michigan up to date.

Like Podcasts? Add the Michigan Medicine News Break oniTunes or anywhere you listen to podcasts.

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Should Pregnant and Breastfeeding Patients Get the COVID-19 Vaccine? - University of Michigan Health System News


Covid virus will stay with us for next 10 years: BioNTech CEO –

Saturday, December 26th, 2020

As the world grapples with the pandemic amid the origin of newer and potentially lethal strains, BioNTech CEO Ugur Sahin has said that the deadly virus is going to stay with us for the next decade at least.

In a virtual press conference this week, Sahin spoke about the potential virus deadline when asked when life could return to normal.

"We need a new definition of normal. The virus will stay with us for the next 10 years," he told mediapersons.

Sahin also said that the vaccine can be adjusted for the new UK variant in about six weeks.

"In principle, the beauty of the messenger technology is that we can directly start to engineer a vaccine which completely mimics this new mutation - we could be able to provide a new vaccine technically within six weeks," he was quoted as saying in media reports.

Sahin said he was confident that the new variant of the Covid-19 strain in the UK would not impact the efficacy of the vaccine.

The new strain of Covid is causing worry all around the world including in India, and it remains to be seen what effect it could have.

After the discovery of a second new variant of the novel coronavirus in Britain, the UK has reported the highest number of Covid-19 fatalities this week, since late April.

Health Secretary Matt Hancock said that the second new variant was reportedly related to travellers from South Africa, and two cases have been reported so far.

"This new variant is highly concerning because it is yet more transmissible and it appears to have mutated further than the new variant that has been discovered in the UK," he said this week.

As a result, Johnson imposed Tier Four restrictions om London and other parts of England.

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Covid virus will stay with us for next 10 years: BioNTech CEO -


Key Genes Related to Severe COVID-19 Infection Identified – The Scientist

Wednesday, December 16th, 2020

More than a year after the first cases of COVID-19 were detected, researchers are still trying to understand why some people infected with the virus become critically ill, while others have little to no symptoms. Scientists have turnedto look at the genes of patients with severe COVID-19 to understand if their bodies mount an immune defense differently than healthy patients do. A genome-wide association study published in Natureon December 11 finds that variants of five key genes responsible for antiviral immunity and lung inflammation are associated with severe COVID-19.

The findings offer potential therapeutic targets to create an effective COVID-19 treatment. Our results immediately highlight which drugs should be at the top of the list for clinical testing, Kenneth Baillie, a consultant in critical care medicine and a senior research fellow at the University of Edinburgh, tells Reuters.

Baillie and his colleagues analyzed the DNA of 2,244 patients across 208 UK intensive care units and compared it to matched controls who did not have a positive COVID-19 PCR test on file. They identified eight loci where variants were more common among the intensive care patients, of which five were in genes linked to the immune systemIFNAR2, TYK2, OAS1, DPP9, and CCR2.

An analysis looking into the relationship between the activity of certain genes and severe COVID-19 pointed to a lower expression of IFNAR2, a gene that encodes a building block of a receptor for interferons, which act as emergency flares to warn the immune system of an intruder and have been a target for researchers hoping to develop a COVID-19 treatment. However, administering interferon to hospitalized COVID-19 patients did not reduce mortality, according to a large clinical trial published earlier this month.

The researchers also homed in on a possible link between severe COVID-19 and higher expression levels of TYK2and CCR2, which encode proteins used in cytokine signaling, which drives inflammation and can lead to lung injury. The anti-inflammatory drug baricitinib, typically used to treat rheumatoid arthritis, inhibits the protein encoded by the TYK2gene and has shown promising results in treating COVID-19 when paired with remdesivir, a broad spectrum antiviral that has shown limited effectiveness against the virus by itself, according to a study published December 11 in The New England Journal of Medicine.

While the Naturestudy may offer clues for the genetic underpinnings of severe COVID-19 infection, finding an effective treatment in humans may still be years away. There is no guarantee that when a gene is found, targeting that gene will result in therapeutic efficacy, Tom Hemming Karlsen, a physician at the University of Oslo who did not participate in the new work, tells The Washington Post. What genetics studies like this then do is they help us find very specific starting points for further investigation.

The authors' investigation indicated that there is a causal role for IFNAR2 and TYK2. Sara Clohisey, a research fellow at the University of Edinburgh and a coauthor of the Nature study, notes that there are likely many other factors beyond these gene variants that contribute to COVID-19 disease severity.

A chunk of the answer is in our genes, but its unlikely that a single element is fully responsible for the development of severe COVID-19, she tells the Post. Its more likely to be a combination of factors, which may include genetics as well as age, obesity, gender, and other characteristics.

Correction (December 15): A previous version of this article misinterpreted Sara Clohisey's comments about the causality of her findings.The Scientistregrets the error.

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Key Genes Related to Severe COVID-19 Infection Identified - The Scientist


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