Category Archives: Genetic Medicine

On May 6, 2020, Benjamin Neale will discuss progress in mapping genetic risk factors for autism, schizophrenia and bipolar disorder.

His talk is part of the Simons Foundation Autism Research lecture series.

The past decade has seen rapid progress in mapping genetic risk factors for autism, schizophrenia and bipolar disorder. In this talk, Benjamin Neale will review this progress, delving into how study designs and genetic variants are teaching us about different aspects of mental health. With that backdrop, he will then introduce the International Common Disease Alliance (ICDA), a nascent effort to bring the community together to tackle the challenge of moving from genetic maps to biological mechanisms and medicine. The ICDA has developed a set of recommendations for realizing the promise of human genetics to transform our understanding of and treatment for common disorders, such as autism.

Registration is required for this free event.Further instructions and access to join the webinar will be sent to all registrants upon sign up.

Benjamin Nealeis an associate professor in the Analytic and Translational Genetics Unit at Massachusetts General Hospital, where he directs the Genomics of Public Health Initiative. He is also an associate professor in medicine at Harvard Medical School and an institute member at the Broad Institute. Neale is strongly committed to gaining insights into the genetics of common, complex human diseases. Neale and Mark Daly, both of whom are associated with the Broad Institute and Massachusetts General Hospital, lead the ADHD Initiative. This collaborative effort focuses on genomic studies of attention deficit hyperactivity disorder (ADHD).

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Progress in understanding the genetic basis of mental health - SFARI News

An antiviral drug called remdesivir isthe first treatment to show efficacy against the coronavirus.

Preliminary results from a clinical trialcomparing the drug with a placebo suggest that remdesivirspeeds recovery from COVID-19 by 31 percent, the U.S. National Institute ofAllergy and Infectious Diseases said April 29 in a news release.

The international trial randomly assigned1,063 people hospitalized with COVID-19 to get intravenous infusions of eitherremdesivir or a placebo. In the remdesivir group, the median time to recoverywas 11 days, compared with 15 days for those on the placebo. Recovery wasdefined as being discharged from the hospital or being well enough to resumenormal activity. Eight percent of people in the remdesivir group died, comparedwith 11 percent in the placebo group.

Although a 31 percent improvementdoesnt seem like a knockout 100 percent, it is a very important proof ofconcept, Anthony Fauci, director of the NIAID, said April 29 during a newsbriefing at the White House. It has proven that a drug can blockthis virus.

Normally, researchers would have waitedto make the announcement until the results had been reviewed by otherscientists, but the team chose to make the announcement early, Fauci said.Whenever you have clear-cut evidence that a drug works, you have an ethicalobligation to immediately let the people who are in the placebo group know sothat they can have access.

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Remdesivir will now be the standard ofcare by which other drugs are judged, Fauci said. The trial will be adapted to addto the remdesivir treatment an antibody that may protect against inflammation,he said.

Remdesivir, developed by biopharmaceuticalcompany Gilead Sciences, headquartered in Foster City, Calif., mimics abuilding block of RNA, the coronaviruss genetic material. When the viruscopies its RNA, remdesivir is incorporated instead of the usual RNA components,stopping the viruss replication.

In studies in lab dishes and animals,remdesivir has been effective against a wide variety of RNA-containing viruses,including those that cause MERS and SARS. Its passed every single milestone.It works against every coronavirus weve tested, says Mark Denison, avirologist at Vanderbilt University Medical Center in Nashville, who was notinvolved in the study.

Remdesivir has been most effective inanimal studies when given early in infections, Denison says. The drug can stopor slow viral replication but doesnt block the bodys overzealous immunesystem responses that cause additional damage for many severely ill COVID-19patients. He likens remdesivir to a fire extinguisher. If theres a fire, andyou put it out with the fire extinguisher, youre not going to get burned. Butif you fall in [the fire] and burn your arm, you can apply the fireextinguisher and maybe youll limit the burn, but you cant heal it.

If the drug can be given early in the infection difficult to do with a drug like remdesivir that is given intravenously and must be administered by trained medical professionals then people might never become ill enough to need to go to the hospital. You [could] convert this from being a lethal disease, to being a manageable, survivable disease, Denison says.

A similar compound given as an oral drugmight even be used to prevent infections, Denison says.

Gilead also announced results of another remdesivir trial on April 29. That study compared a five-day course of remdesivir with 10 days of treatment. There was no control group that didnt get the drug. It took 10 days for half of people on the shorter course of remdesivir to have clinical improvement compared with 11 days for those in the longer-treatment group.

The study demonstrates the potentialfor some patients to be treated with a 5-day regimen, which couldsignificantly expand the number of patients who could be treated with ourcurrent supply of remdesivir. This is particularly important in the setting ofa pandemic, to help hospitals and health care workers treat more patients inurgent need of care, the company said in a news release.

Of the 200 people in the five-daytreatment group, 129 went home from the hospital by day 14, while 106 of the197 people who got the longer treatment were discharged by day 14.

Treating earlier was also beneficial. Sixty-twopercent of patients who got treatment within 10 days of their symptoms startingwere able to go home after two weeks in the hospital, but only 49 percent ofthose who got treatment later in the infection were discharged after two weeksin the hospital.

A smaller, incomplete study publishedApril 29 in the Lancet appears tocounter the results of the NIAID study. The Lancetstudy, conducted in 10 hospitals in Wuhan, China, where the pandemic firststarted, found nostatistically significant improvement in recovery time in severely illCOVID-19 patients given remdesivir, compared with those who got a placebo.

In that study, the median time torecovery for patients taking remdesivir was 21 days, compared with 23 days forthose getting a placebo. There was a trend that remdesivir sped recovery forpeople who had symptoms for less than 10 days, but that result didnt meetstatistical thresholds. That trial stopped early because Wuhans lockdowneffectively stopped transmission so that researchers werent able to recruitenough patients to fill the trials slots. As a result, the trial lacked thestatistical power to detect differences between the groups, Denison says.

Previous results from a study of patients given remdesivir for compassionate use when no clinical trial was available showed that 36 of 53 people given the drug needed less supplemental oxygen afterward, researchers reported April 10 in the New England Journal of Medicine.

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Remdesivir is the first drug found to block the coronavirus - Science News

AstraZeneca will oversee global development, manufacturing, and distribution of the COVID-19 vaccine candidate that was created by researchers at University of Oxford, and is now being studied in a human clinical trial launched last week, the partners said today.

AstraZeneca, the University, and its spinout company Vaccitechwhich has joint rights to the platform technology behind the vaccinecandidate, ChAdOx1 nCoV-19said they will start work immediately while hammering out final terms of their collaboration agreement. The partnership is designed to enable rapid production and distribution of the vaccine should it prove effective in clinical studies.

Our hope is that, by joining forces, we can accelerate the globalization of a vaccine to combat the virus and protect people from the deadliest pandemic in a generation, AstraZeneca CEO Pascal Soriot said in a statement. As COVID-19 continues its grip on the world, the need for a vaccine to defeat the virus is urgent. This collaboration brings together the University of Oxfords world-class expertise in vaccinology and AstraZenecas global development, manufacturing and distribution capabilities.

ChAdOx1 nCoV-19 has been developed by the Universitys Jenner Institute, whose researchers last week partnered with colleague from the Universitys jointly with the Universitys Oxford Vaccine Group to launch the COV001 Phase I/II trial (NCT04324606.)

The single-blinded, randomized, multi-center study is designed to determine the efficacy, safety and immunogenicity of the vaccine candidate in healthy adult volunteers aged 1855 years across five trial centers in Southern England. Data from the Phase I trial could be available next month, AstraZeneca predicted, with advancement to late-stage trials expected to occur by the middle of this year.

By June, July we will already have a very good idea of the direction of travel in terms of its potential efficacy, Soriot told BBC Radio 4.

The vaccine has shown positive results in six rhesus macaque monkeys inoculated with single doses, all of which remained healthy 28 days following treatment, followed by exposure to SARS-CoV-2, Vincent J. Munster, PhD, Chief, Virus Ecology Unit at the NIHs National Institute of Allergy and Infectious Disease, toldThe New York Timesthis week.

The trialbegan recruiting patients on April 23, after U.K. Health Secretary Matt Hancock pledged 20 million ($25 million) in government funding to support ChAdOx1 nCoV-19 development.

In the long run, a vaccine remains our best hope of defeating this virus for good, Hancock stated. I am determined to do everything in my power to develop an effective vaccine and get it to the people of the U.K. as soon as possible. I want the U.K. to lead the world in developing a coronavirus vaccineand I will back our scientists to the hilt in doing so.

ChAdOx1 nCoV-19 uses a viral vector based on a weakened version of the adenovirus containing the genetic material of SARS-CoV-2 spike protein. After vaccination, the surface spike protein is produced, which primes the immune system to attack COVID-19 if it later infects the body. The recombinant adenovirus vector (ChAdOx1) is designed to generate a strong immune response from a single dose and to not replicate, in order to preclude causing an ongoing infection in the vaccinated individual.

According to AstraZeneca, vaccines made from the ChAdOx1 virus have been given to more than 320 people to date and have been shown to be safe and well toleratedalthough they can cause temporary side effects such as a temperature, flu-like symptoms, headache or sore arm, the company acknowledged.

Under its agreement with the University, AstraZeneca agreed to provide the U.K. with access to the vaccine as soon as possible should it succeed in clinical trials. AstraZeneca also agreed to work with global partners on the international distribution of the vaccine, with emphasis on making it available and accessible for low- and medium-income countries.

The University of Oxford and AstraZeneca have a longstanding relationship to advance basic research and we are hugely excited to be working with them on advancing a vaccine to prevent COVID-19 around the world, added Mene Pangalos, AstraZeneca executive vice president, BioPharmaceuticals R&D.

Calquence and antibodies

By partnering with Oxford, AstraZeneca signaled its intent to accelerate efforts to bring a COVID-19 treatment to market.

On April 14, AstraZeneca announced plans for a randomized, global clinical trial to assess Calquence (acalabrutinib) as a treatment for cytokine storm associated with COVID-19 infection in severely ill patients. The Phase II CALAVI trial (NCT04346199) is based on early clinical data withCalquence, which according to the company showed that a decrease in inflammation caused by BTK inhibition appeared to reduce the severity of COVID-19-induced respiratory distress in a small number of patients at Walter Reed Army Medical Center.

We are encouraged by anecdotal suggestions that BTK inhibitors could be effective in COVID, Andrew Berens, MD, a Senior ResearchAnalystatSVB Leerinkcovering targeted oncology drug developers, and colleagues wrote this morning in an investor note.

The CALAVI trialtwo arms totaling 428 patientsaims to evaluate the efficacy and safety of addingCalquenceto best supportive care (BSC); the primary endpoint measures the use of assisted ventilation or death.

Calquence is a next-generation, highly selective Brutons tyrosine kinase (BTK) inhibitor indicated for Mantle cell lymphoma patients who have received at least one prior therapy, and chronic lymphocytic leukemia or small lymphocytic leukemia. Calquence generated $88 million in product sales during the first quarter, more than triple the $29 million generated in Q1 2019. The drug generated $164 million last year, its first full year on the market.

On April 8, AstraZeneca said it was working to develop coronavirus-neutralizing monoclonal antibodies through the Defense Advances Research Project Agencys Pandemic Prevention Platform (P3). AstraZeneca said it was exploring three potential sources for antibodies: Patients who have recovered from COVID-19, immunized humanized mice, and lab techniques such as phage display: AstraZeneca is aiming for clinical evaluation in the next 3 to 5 months.

AstraZeneca also disclosed antibody collaborations with external partners, saying that The Chinese Academy of Sciences, and Vanderbilt University Medical Center had provided genetic sequences for antibodies they have discovered against SARS2-CoV-2 for furtherin silicoandin vitroassessment, while the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the University of Maryland School of Medicine were conducting preclinical safety and efficacy assessments of antibody candidates discovered by AstraZeneca through internal research.

AstraZeneca prevailed over several other pharmaceutical giantsmany of them U.S.-basedalso seeking to partner with Oxford in the global manufacturing and distribution of its vaccine, theFinancial Timesreported, citing an unnamed source.

In its latest partnership, AstraZeneca said it had agreed with the University of Oxford to operate on a not-for-profit basis for the duration of the COVID-19 pandemic, with only the costs of production and distribution being covered. The University and its spinout Vaccitech have agreed to receive no royalties from the vaccine during the pandemic.

We believe this vaccine candidate provides significant validation for our ChAdOx platform, which is one of the few to have already induced neutralizing antibodies against coronavirus spike proteins in human studies for MERS, asserted Vaccitech CEO Bill Enright. We are committed to doing all we can to support our scientific founders at the Jenner Institute in order to overcome this unprecedented global crisis.

Oxford also committed to reinvesting any royalties it receives from the vaccine once the pandemic ends directly back into medical researchincluding through the creation of a Pandemic Preparedness and Vaccine Research Centre to be developed in collaboration with AstraZeneca.

Sadly, the risk of new pandemics will always be with us, and the new research center will enhance the worlds preparedness and our speed of reaction the next time we face such a challenge, said Professor Sir John Bell, Regius Professor of Medicine at Oxford University. Our partnership with AstraZeneca will be a major force in the struggle against pandemics for many years to come. We believe that together we will be in a strong position to start immunizing against coronavirus once we have an effective approved vaccine.

AstraZenecas partnership with the University and Vaccitech is the first partnership formed since the U.K. government launched its dedicated Vaccines Taskforce two weeks ago, with the aim of helping find, test and deliver a new COVID-19 vaccine.

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AZ, University of Oxford, and its Spinout to Develop COVID-19 Vaccine - Clinical OMICs News

By Peter Schelden on 04/30/2020 2:00 PM

Source: MedicineNet Health News

Even as the virus that causes COVID-19 continues to infect and kill across all habitable continents, the specter of a new and perhaps more deadly SARS-CoV-2 mutation looms over the horizon.

How worried should we be?

All viruses are prone to mutate. But RNA viruses like SARS-CoV-2 mutate more frequently than anything else in the world.

RNA viruses include a wide variety of familiar infections like:

Some estimates say RNA viruses account for up to 44% of all emerging infectious disease.

When a virus mutates, its new genetic changes usually cause it to be less harmful, or even harmless. But there is always a small chance that a mutation could cause a more harmful strain, which is what many researchers believe caused the Spanish flu of 1918 to become the deadliest modern pandemic.

Virus genes are not 'set' as they are for life forms like humans. They mutate so often that they are sometimes called a 'quasispecies,' in which a 'population of particles' infect a host that are nonidentical but related. The whole viral population may share roughly similar genetic traits, with a lot of variation, according to Vincent Racaniello, Ph.D., Higgins Professor of Microbiology & Immunology at Mt. Sinai School of Medicine of CUNY.

Sometimes mutations causeserious difficulties in treating or inoculating people from infection, or it can provoke more dangerous versions of the disease. Some of these problems have sometimes occurred in HIV, hepatitis C, and measles, which are all caused by RNA viruses, as is COVID-19, the novel coronavirus.

But virus experts say that even if a mutation causes a death rate increase, this does not necessarily make a virus more deadly overall. Killing your host quickly can make it hard to spread to a new one, and natural selection often prevents viruses from becoming more deadly as they mutate.

In fact, mutations often prevent the virus from successfully spreading, or lead to a weaker version of the original. Scientists hunt for weak replicants of viruses for their potential as vaccine strains.

All viruses mutate at different rates. More than 25 RNA viruses have been measured in labs, with individual viruses counted for mutations. Scientists have found that anywhere from one in ten thousand to one in a million RNA virus particles contains a mutation, depending on the type.

Here are some mutation rate estimates for other known viruses. This number tells you roughly how many viral particle mutants will exist in a given viral population:

This does not tell the whole story about a virus' potential to mutate, but it offers a rough idea of how easily and often they do.

COVID-19 is not as well-studied as these other diseases. But an estimated range of its mutation rate has emerged from a study of 30 publicly available samples of SARS-CoV-2. Researchers at Johns Hopkins estimate the mutation rate of COVID-19 at:

The facts about COVID-19 are being reinterpreted with better understanding every day. An early study that claimed the existence of a supposed "strain S" and "strain L" of the virus that causes COVID-19 was published March 3. It claimed to identify one strain in China that had become more aggressive than the other.

But that study was widely criticized for exaggerating the significance of its claims, as well as for using a small sample pool.

A mutant variation of the COVID-19 virus that causes additional concern has yet to be found, according to researchers. This is based on the known mutations of SARS-CoV-2, which number over 100.

"Different clades (evolutionary descendants) emerge as viruses evolve," says one Johns Hopkins study. "This is entirely normal and does not mean there are new strains of SARS-CoV-2 that are more pathogenic than others circulating right now."

That doesn't mean scientists aren't interested in how COVID-19 mutates. In addition to searching for weak mutations that might serve as vaccines, researchers can track the spread of the disease by following its mutations. This can help us know where new infections are coming from, among other important details about the novel coronavirus.

Read more here:
When COVID-19 Mutates, What Are the Risks? - MedicineNet

Dr. Hugo J. Bellen, professor of molecular and human genetics and neuroscience at Baylor College of Medicine and Howard Hughes Medical Institute investigator, has been elected as one of the newest members of the American Academy of Arts and Sciences, one of the countrys most prestigious honorary titles. He is among 276 artists, scholars, scientists, and leaders in the public, non-profit, and private sectors elected to the Academy for the class of 2020.

Founded in 1780, the Academy was created to honor exceptionally accomplished individuals and engage them in advancing the public good. Today, the Academy continues to dedicate itself to recognizing excellence in a broad array of fields.

Dr. Bellens groundbreaking research is addressing issues related to both rare and common neurological diseases facing humans today, said Dr. Paul Klotman, president, CEO and executive dean of Baylor College of Medicine. He is an excellent leader and mentor at Baylor College of Medicine and an extremely deserving recipient of this honor from the Academy.

Bellen is one of the world's premier researchers in Drosophila, or fruit fly, genetics. His group has made major contributions to the understanding of nervous system development, synaptic transmission and mechanisms of neurodegeneration. As the head of the Drosophila Gene Disruption Project, his laboratory has developed numerous sophisticated genetic tools and generated tens of thousands of reagents that have transformed Drosophila biology. His reagents are used by nearly every fly biologist.

Bellen's current research focuses on the discovery of new rare human disease genes and elucidating the pathogenic mechanisms of neurodevelopmental and neurodegenerative diseases using fruit flies, in collaboration with human geneticists worldwide. His lab is the home of the Model Organism Screening Center for the Undiagnosed Diseases Network of the National Institutes of Health. In the past few years, he has made major strides in solving key problems related to nearly 25 rare human diseases, and these studies also have revealed probing knowledge about Friedreich ataxia, Alzheimer disease, Amyotrophic Lateral Sclerosis and Parkinson disease.

I would like to express my deepest gratitude to many, said Bellen, the March of Dimes Chair at Baylor College of Medicine. Im extremely indebted to my graduate students and postdoctoral fellows whose accomplishments through their creative thinking, motivation and scientific acumen have made many of our dreams come true. Second, I would like to extend my sincere thanks to my colleagues who have created a collaborative and productive no-nonsense environment at Baylor College of Medicine and the Neurological Research Institute. Lastly, thetireless intellectual and moral support ofmy spouse, Catherine, combined with herexquisitesixth sense have been invaluable in shaping my career."

Current Academy members represent todays innovative thinkers in every field and profession, including more than 250 Nobel and Pulitzer Prize winners. Baylor College of Medicine faculty who are American Academy of Arts and Sciences members include Dr. James Lupski, Dr. Bert W. OMalley, Dr. JoAnne Richards, Dr. Peter J. Hotez, and Dr. Huda Y. Zoghbi.

See a full list of this years new members.

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Bellen elected to the American Academy of Arts and Sciences - Baylor College of Medicine News

Middlefield Dr. Heng Wang, a board certified pediatrician and the Medical Director of the DDC Clinic located in Middlefield, OH, announced today that their Amish Genetic Disease Panel will now test for 160 rare conditions. This important tool allows faster diagnosis of unidentified genetic conditions at a reduced cost. DDC Clinic delivers personalized and life-changing medical care to special needs children affected by rare genetic disorders.

Were very excited to be able to now screen for an additional 40 conditions as part of this panel, said Dr. Wang. Early diagnosis leads to early treatments, and those effective treatments can be lifesaving.

Dr. Wang credited the hard work of his staff with bringing this project to fruition months ahead of schedule. This project was partially funded by the Elisabeth Severance Prentiss Foundation and the Fowler Family Foundation. Their support allows us to keep the cost of the new panel the same as the previous panel.

The improved Amish Genetic Disease Panel will be used in DDC Clinics collaboration with the Care Center in Middlefield. Parents of newborn infants at the birthing center can have a sample of their babys cord blood sent to DDC Clinic for analysis. Parents would then know if their child is affected by any of these 160 rare conditions. If a condition is identified, no additional testing would be needed and support services could be initiated early in the babys life. Thanks to our generous donors and the United Way of Geauga County, parents are asked to pay only $25.00 for this testing as part of their birthing fee.

The Amish Genetic Disease Panel has proven to be an important tool and is a great example of personalized medicine in action. It is a resource for doctors serving Amish and Mennonite patients in both Geauga County and neighboring communities.

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Amish Genetic Disease Panel created by DDC Clinic can now test for 160 rare conditions - The Weekly Villager