Daily Archives: March 26, 2020

A new international project aims to enroll 500 COVID-19 patients to search for genetic mutations that make some people more vulnerable to severe infection.

HHMI scientists are joining many of their colleagues worldwide in working to combat the new coronavirus.Theyre developing diagnostic testing, understanding the viruss basic biology, modeling the epidemiology, and developing potential therapies or vaccines. Over the next several weeks, we will be sharing stories of some of this work.

Hundreds of clinicians worldwide are banding together in an effort to study some types ofseverecases of the new coronavirus disease.

The project, led by Howard Hughes Medical Institute (HHMI) Investigator Jean-Laurent Casanova at The Rockefeller University, seeks to identify genetic errors that make some younger patients especially vulnerable to the virus that causes COVID-19, the infectious respiratory illness also known as coronavirus disease 2019.

Casanova aims to enroll 500 patients internationally who meet three broad criteria: theyre less than 50 years old, have been diagnosed with COVID-19 and admitted to an intensive care unit, and have no serious underlying illnesses, such as diabetes, heart disease, or lung disease.

By studying these patients' DNA, scientists may pinpoint genetic mutations that make some people more susceptible to infection. Such information could one day help doctors identify people who are most at risk of developing severe coronavirus disease, says Casanova, a pediatrician at Rockefeller. It could also offer clues for scientists searching for new therapeutics. For example, if patients cells arent making enough of a particular molecule, doctors may be able to offer a supplement as treatment.

Were going to try to find the genetic basis of severe coronavirus infection in young people.

Jean-Laurent Casanova, HHMI Investigator at The Rockefeller University

That day may still be years away. This is not a short-term effort, Casanova says. Some scientists have hypothesized that COVID-19 might be a seasonal illness, with infections ebbing in the spring and summer, and then returning in the fall. But Casanovas team is optimistic. They have already begun enrolling patients and have started sequencing their exomes spelling out all of the DNA letters in every gene in a persons genome. Were going to try to find the genetic basis of severe coronavirus infection in young people.

Late last year, when the first coronavirus infections began cropping up in China, Casanova started reaching out to his colleagues there. Though the most severe cases seemed to concentrate among older adults and those with other conditions, Casanova was interested in the outliers kids and young adults hit hard by the illness who didnt have any of the usual risk factors, such as age or underlying illness.

His team kicked off a new project to study these mysterious cases, and in January just weeks after the Wuhan outbreak began enrolling patients. Clinicians mailed patient blood and DNA to his lab, and researchers there and elsewhere began processing samples the first steps needed for scientists to peer into patients genomes. Now, the project is global, and Casanova is collaborating with scientists and healthcare workers from Europe to Africa, Asia, and Oceania.

We will recruit children and adults <50 yo without risk factor admitted to ICU for idiopathic #COVID19. We will test the hypothesis that they carry inborn errors of immunity to this virus. Please refer patients to @casanova_lab and please RT. pic.twitter.com/DXPoFKieEy

Hunting for the genetic underpinnings of severe infectious diseases is nothing new for Casanovas team. What were doing with coronavirus is what my lab has been doing for 25 years with other infections, he says.

They look for weak spots in peoples immune systems small genetic changes that make people more vulnerable to disease. His group has previously searched the genomes of patients infected with viruses, bacteria, fungi, and even parasites. The infection closest to COVID-19 his team has studied is severe influenza pneumonitis, for which theyve discovered three genetic links. Theyve also identified specific genetic errors that can predispose patients with herpes to viral encephalitis. And theyve found that children with mutations in an immunity gene called IFN-gamma are vulnerable to the bacteria that cause tuberculosis. These children make low levels of the IFN-gamma protein, which is critical for fighting off bacterial infections.

Casanovas team has put these findings to use clinically. For example, the researchers have shown that tuberculosis patients with these genetic errors can benefit from treatment with IFN-gamma. Hes hoping to identify problematic genes in patients with severe coronavirus infection that can bring similar clinical gains. These genes could tell scientists which cellular defenses are crucial for warding off COVID-19 and pave the way for understanding whether such defenses are derailed in older adults or patients with an underlying medical condition.

In the US and around the world, severe coronavirus disease seems to hit older patients hardest, though scientists have reported some country-to-country variation. As of March 24, more than 44,000 confirmed and presumptive positive cases have been reported in the US. Fatality has been highest in people over 85 years old, according to a recent report from the Centers for Disease Control and Prevention (CDC). Though young people may be more susceptible than scientists once suspected,the older you are, the higher the likelihood you have a severe form of the disease, Casanova says.

Last week, Rockefeller closed all labs except those working on the coronavirus, and Casanova whittled his team to a skeleton crew of about eight people down from 35 who rotate so there is only one person per room at a time. He and his lab members are following CDC recommendations, and taking protective measures to keep themselves and others safe, including social distancing, washing hands, and disinfecting surfaces. Theyve also taken to Twitter to get the word out about their work. A tweet posted from Casanovas lab last week about recruiting new patients to their study has since been retweeted more than 400 times.

Soon, theyll be testing their genetic theory on a pandemic thats occurring in real time. Im grateful weve been able to start this new project so quickly, he says. God willing, it will be of clinical usein two or three years.

Follow the Casanova lab on Twitter (@casanova_lab) to learn the latest about their work. Doctors interested in enrolling patients in the study can contact Jean-Laurent Casanova at jean-laurent.casanova@rockefeller.edu.

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Patients with Severe Forms of Coronavirus Disease Could Offer Clues to Treatment - Howard Hughes Medical Institute

The coronavirus pandemic has led to a spike in sales of products, includinghand sanitizer, toilet paper and pasta.

More than likely, however, there is no need to buy too much of anything, Dr. Amy Edwards, a pediatric infectious disease specialist at University Hospitals who works with the UH Roe Green Center for Travel Medicine & Global Health,tells Grow. "My advice would be to be vigilant, but calm, and not to panic."

To protect yourself from coronavirus, health professionals say the most important thing to do is wash your hands regularly. Don't forget to clean your phone regularly, too. "I clean my phone at least once a day," says Edwards. She advises others to do the same and many medical experts agree.

"It's often said that your phone is like a third hand because you're constantly touching it," says cleaning influencer Melissa Maker.

People take their phones out to eat, on the train, and to the bathroom. As a result, cellphones carry more than 17,000 bacterial gene copies each, according to a 2017 study. The report concluded that this "may play a role in the spread of infectious agents."

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Cleaning phones daily, at least, is smart, says Edwards."Certainly, if you are letting a lot of people use your phone, you would want to clean it to help prevent spread."

It's often said that your phone is like a third hand because you're constantly touching it.

Melissa Maker

Cleaning Influencer

If you want to clean your phone effectively, Maker says not to use a Lysolwipe or disinfectant wipe, as it may strip the coating of your phone over time. "The chemicals that are used in those disinfectant wipes are not meant to be used on electronics," she says.

Until recently, Apple advised against the use oftraditional cleaning products or compressed air.But earlier this month, Apple updated its instructions to say you can clean your phone with disinfectant wipes, as long as you wipe gently and avoid getting any liquid in charging ports.

GuidelinesforAndroidhandsets still advise steering clear of disinfectant wipes.

One alternative: Cleaning wipes that are specifically made for electronic devices. A 210-pack of individually wrapped lens- and screen-cleaning wipes is $16.99 on Amazon right now.

Maker suggests using a microfiber cloth. "Microfiber has the ability to pick up bacteria," Makers says. "Then you can launder the microfiber cloth."A six-pack of microfiber cleaning clothes is $9.99 on Amazon right now.

A damp microfiber cloth can remove microorganisms including viruses and bacteria and is more effective than a cotton rag, microbiologist Kristen Gibson told the The Wall Street Journal. It won't damage your phone the way a Lysol wipe might, either.

You can also pair onewith a homemade cleaner that is equal parts water and rubbing alcohol. Dip the cloth in the mixture, make sure it's not excessively wet, and then wipe down all parts ofyour phone. This will serve as an effective disinfectant.

And, of course, make sure you frequently wash your hands.

The article Clean Your Phone At Least Once a Day, Says Infectious Disease Specialist originally appeared on Grow by Acorns + CNBC.

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Clean your phone 'at least once a day,' medical experts say. Here's howwithout damaging the screen - CNBC

- Leveraging proprietary technology and manufacturing platform to develop transformativegene therapies for multiple rare diseases with high unmet needs -

- Pipeline led by Phase 3 gene therapy candidate for treatment of recessive dystrophic epidermolysis bullosa (RDEB), with a BLA filing targeted for 2021 -

- Backed by world-class group of biotech operators and investors -

EXTON, Pa., March 25, 2020 (GLOBE NEWSWIRE) -- Castle Creek Biosciences, Inc., a privately held, late-stage gene therapy company, announced that it has received a new investment of $75 million to support the advancement of its clinical development pipeline. Castle Creek Biosciences is a portfolio company of Paragon Biosciences, which led the $55 million equity investment from Fidelity Management & Research Company and Valor Equity Partners, along with a $20 million venture loan from Horizon Technology Finance Corporation (HRZN).

Castle Creek Biosciences is leveraging its proprietary technology platform and commercial-scale manufacturing infrastructure to develop personalized gene therapies for rare diseases with high unmet needs. The company plans to use the funding to advance and expand its gene therapy pipeline, led by the Phase 3 clinical development of FCX-007 (NCT04213261), its gene therapy candidate for the treatment of RDEB. It will also use the funding to expand its current good manufacturing practices (cGMP) infrastructure located in the greater Philadelphia region.

Clinical results from the ongoing Phase 1/2 clinical trial for FCX-007 continue to show positive trends in safety and wound healing in RDEB patients. Current data from this clinical trial were presented at the inaugural World Congress on Epidermolysis Bullosa held in London during January of 2020. FCX-007 was administered to 10 non-healing chronic wounds of which eight achieved complete wound closure 12 weeks post-administration (80%) vs. no wound closure in intra-patient, matched non-treated wounds (0%). FCX-007 continues to be well tolerated up to 52 weeks post administration.

We are proud to have the strategic support of world-class investors whose impact enables our efforts to transform the lives of patients and the future of medicine, said John Maslowski, Chief Executive Officer of Castle Creek Biosciences. We are steadfast in our commitment to the epidermolysis bullosa community and will continue to keep patients, caregivers and clinicians informed on the progress of our current programs, including FCX-007 and diacerein topical ointment, while we expand the scope of our gene therapy platform.

Castle Creek Biosciences is led by a strong executive leadership team with a proven record of developing innovative and potentially life-changing treatments for conditions with the greatest medical need, said Jeffery Aronin, Chairman and Chief Executive Officer of Paragon Biosciences. As investors, we are excited by the progress that the team has made and are committed to growing the Castle Creek Biosciences platform to address multiple rare genetic diseases.

About Castle Creek Biosciences, Inc. Castle Creek Biosciences is a privately held company that develops and commercializes gene therapies for patients with rare and serious genetic diseases. The companys lead gene therapy candidate, FCX-007, is being evaluated for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), the most severe and debilitating form of epidermolysis bullosa (EB). The company is also advancing clinical research evaluating a diacerein topical ointment, CCP-020, for the treatment of epidermolysis bullosa simplex (EBS) and other forms of EB. In addition, Castle Creek Biosciences is developing FCX-013, a gene therapy for the treatment of moderate to severe localized scleroderma. Castle Creek Biosciences is a portfolio company of Paragon Biosciences. For more information, visit castlecreekbio.com or follow Castle Creek on Twitter @CastleCreekBio.

About Paragon BiosciencesParagon is a life science innovator that invests in, builds, and advises bioscience companies. Our mission is to serve patients living with severe medical conditions which do not yet have adequate treatments. Paragons portfolio of independently-run bioscience companies focus on biopharmaceuticals, AI-enabled life science products, and advanced treatments such as cell and gene therapies. We help people live longer, healthier lives. For more information, please visit: ParagonBioSci.com.

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Castle Creek Biosciences Announces $75 Million Investment to Advance Development of Multiple Gene Therapy Candidates for Rare Diseases - Yahoo Finance

Though the number of human genomes sequenced continues to rise rapidly since the completion of the Human Genome Project a scientific endeavor spanning multiple decades and countries aimed at detailing human DNA in 2003, less than 10 percent of those genomes to date correspond to individuals of Asian descent. The GenomeAsia 100K Project, a non-profit consortium, seeks to change this lack of knowledge surrounding a major portion of the worlds ethnicities. The conglomeration of researchers and private sector executives from around the world from Seoul, South Korea to the University plans to add 100,000 novel genomes from individuals of Asian ethnicity to new open-access databases.

Academic institutions and private sector companies came together in 2016 to launch the GenomeAsia 100K Project. While the research organization MedGenome and Nanyang Technological University in Singapore originally founded the non-profit consortium, representatives from other businesses and schools including Genentech, Macrogen and the University of California, San Francisco have joined the association.

Since genome sequencing can reveal the unique characteristics of each persons genetic material, it can help determine a persons ancestry and the propensity for certain medical conditions. According to GenomeAsia 100K, Asians constitute nearly half of the worlds population, and the distinct ethnicities and communities offer a relatively untapped repository of genetic diversity. The project hopes to provide new insights into inherited diseases as well as those caused by a combination of genetic and environmental factors.

Aakrosh Ratan, assistant professor of public health sciences and researcher for GenomeAsia 100K, explained that in particular, the information the initiative collects may help develop medical treatments based on peoples specific genetic makeup, instead of relying on traditional general treatments that may not target the unique root cause of each patients form of a disease.

The goal of precision medicine is to tailor treatment towards a persons genetic background, and that dream cannot be realized until you have the proper reference databases, Ratan said.

Mutations in humans DNA sequences lead to different copies of the same gene within a person and amongst ethnicities. These different versions of a gene can act as markers of diseases that are inherited or influenced by genetic makeup. For example, the disorder sickle cell anemia is caused by the change of a single point in the DNA sequence. When someone is born with copies of this particular gene from both parents contain the mutation, he or she will suffer from often debilitating pain resulting from red blood cells that cannot effectively transport oxygen.

Ratan explained that genome sequencing can highlight mutations in a persons DNA that may cause illnesses such as sickle cell anemia.

One of the ways we identify the mutations that drive a rare disease is by identifying the mutations and then prioritizing those mutations based on their prevalence in healthy populations, Ratan said. With the medical datasets we have compiled, we can actually improve such analyses for patients of Asian descent.

As of December 2019, the GenomeAsia 100K Project has completed the analysis of 1,739 genomes from 219 populations and 64 countries worldwide. Preliminary findings appeared that same month in the scientific journal Nature. The paper concluded that the sample provided a reasonable framework for sequencing practices and studying the history and health of Asian populations. Ratan and his lab at the University supervised the identification and contributed to the analysis of these genetic variants.

Once the 100,000 genomes have been collected and sequenced, the data will be publicly available as a controlled dataset. As a result, experts investigating topics from heart disease to human evolution can easily access the genome sequences.

One of the real gaps in human genetics studies of disease has been the underrepresentation of non-Europeans, Charles Farber, associate professor of public health sciences, said in an email to The Cavalier Daily. The work of the GenomeAsia 100K Consortium provided critical insight into the extent and nature of genome variation in individuals of Asian ancestry and will be critical in making disease genetic studies more inclusive of all global populations.

Ani Manichaikul, assistant professor of public health sciences in the Center for Public Health Genomics, expressed enthusiasm for the GenomeAsia 100K Project. She claimed that the additional genetic information could augment her research as part of the Multi-Ethnic Study of Atherosclerosis, a cardiovascular disease where fatty deposits accumulate and potentially block arteries. The study currently focuses on Caucasian, African American, Hispanic and Chinese American individuals.

The GenomeAsia project is very useful because there are some instances where particular genetic variants are only observed in particular genetic groups, Manichaikul said. Those markers can be unique to those sequenced through the project, which means we would not have necessarily have observed those particular variants otherwise.

Manichaikul also suggested that expanding existing repositories of hereditary statistics would improve methods of assigning people risk scores for diseases based on their DNA. The National Human Genome Research Institute describes polygenic risk score, which indicates a persons likelihood of certain diseases based on the presence of mutations known to be associated with a given disorder. Companies such as 23andMe have started to provide consumers with this metric, but without a comprehensive database of genomes from different populations, score reliability can decrease.

Since indicators of genetically-linked conditions often appear in certain alleles, or different versions of a gene, knowing whether one has a disease marker can help patients take preventative measures if need be. However, in the absence of comprehensive information on the range of disease markers that appear in different ethnicities, whole populations may lack the potential benefits of this burgeoning healthcare statistic.

The only way we can create risk prediction models that are accurate across populations is if we also have corresponding databases available with individuals that represent that diversity, Manichaikul said.

Following the findings in the preliminary study, GenomeAsia 100K Project collaborators will continue to sequence more genomes of Asian individuals. The hope is that, once researchers have access to the data, insights from 100,000 genomes will drive the development of new therapeutic strategies that will benefit people around the world.

I would like more researchers to have access to this data, Ratan said. This is a resource. Were working to establish these reference datasets, and we would definitely like them to be used.

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Bridging the gap study sequences Asian genomes to diversify genetic databases - University of Virginia The Cavalier Daily

Working at a breakneck pace, a team of hundreds of scientists has identified 50 drugs that may be effective treatments for people infected with the coronavirus.

Many scientists are seeking drugs that attack the virus itself. But the Quantitative Biosciences Institute Coronavirus Research Group, based at the University of California, San Francisco, is testing an unusual new approach.

The researchers are looking for drugs that shield proteins in our own cells that the coronavirus depends on to thrive and reproduce.

Many of the candidate drugs are already approved to treat diseases, such as cancer, that would seem to have nothing to do with Covid-19, the illness caused by the coronavirus.

Scientists at Mount Sinai Hospital in New York and at the Pasteur Institute in Paris have already begun to test the drugs against the coronavirus growing in their labs. The far-flung research group is preparing to release its findings at the end of the week.

There is no antiviral drug proven to be effective against the virus. When people get infected, the best that doctors can offer is supportive care the patient is getting enough oxygen, managing fever and using a ventilator to push air into the lungs, if needed to give the immune system time to fight the infection.

If the research effort succeeds, it will be a significant scientific achievement: an antiviral identified in just months to treat a virus that no one knew existed until January.

Im really impressed at the speed and the scale at which theyre moving, said John Young, the global head of infectious diseases at Roche Pharma Research and Early Development, which is collaborating on some of the work.

We think this approach has real potential, he said.

Some researchers at the Q.B.I. began studying the coronavirus in January. But last month, the threat became more imminent: A woman in California was found to be infected although she had not recently traveled outside the country.

That finding suggested that the virus was already circulating in the community.

I got to the lab and said weve got to drop everything else, recalled Nevan Krogan, director of the Quantitative Biosciences Institute. Everybody has got to work around the clock on this.

Dr. Krogan and his colleagues set about finding proteins in our cells that the coronavirus uses to grow. Normally, such a project might take two years. But the working group, which includes 22 laboratories, completed it in a few weeks.

You have 30 scientists on a Zoom call its the most exhausting, amazing thing, Dr. Krogan said, referring to a teleconferencing service.

Viruses reproduce by injecting their genes inside a human cell. The cells own gene-reading machinery then manufactures viral proteins, which latch onto cellular proteins to create new viruses. They eventually escape the cell and infect others.

In 2011, Dr. Krogan and his colleagues developed a way to find all the human proteins that viruses use to manipulate our cells a map, as Dr. Krogan calls it. They created their first map for H.I.V.

That virus has 18 genes, each of which encodes a protein. The scientists eventually found that H.I.V. interacts, in one way or another, with 435 proteins in a human cell.

Dr. Krogan and his colleagues went on to make similar maps for viruses such as Ebola and dengue. Each pathogen hijacks its host cell by manipulating a different combination of proteins. Once scientists have a map, they can use it to search for new treatments.

In February, the research group synthesized genes from the coronavirus and injected them into cells. They uncovered over 400 human proteins that the virus seems to rely on.

The flulike symptoms observed in infected people are the result of the coronavirus attacking cells in the respiratory tract. The new map shows that the viruss proteins travel throughout the human cell, engaging even with proteins that do not seem to have anything to do with making new viruses.

One of the viral proteins, for example, latches onto BRD2, a human protein that tends to our DNA, switching genes on and off. Experts on proteins are now using the map to figure out why the coronavirus needs these molecules.

Kevan Shokat, a chemist at U.C.S.F., is poring through 20,000 drugs approved by the Food and Drug Administration for signs that they may interact with the proteins on the map created by Dr. Krogans lab.

Dr. Shokat and his colleagues have found 50 promising candidates. The protein BRD2, for example, can be targeted by a drug called JQ1. Researchers originally discovered JQ1 as a potential treatment for several types of cancer.

On Thursday, Dr. Shokat and his colleagues filled a box with the first 10 drugs on the list and shipped them overnight to New York to be tested against the living coronavirus.

The drugs arrived at the lab of Adolfo Garcia-Sastre, director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai Hospital. Dr. Garcia-Sastre recently began growing the coronavirus in monkey cells.

Over the weekend, the team at the institute began treating infected cells with the drugs to see if any stop the viruses. We have started experiments, but it will take us a week to get the first data here, Dr. Garcia-Sastre said on Tuesday.

The researchers in San Francisco also sent the batch of drugs to the Pasteur Institute in Paris, where investigators also have begun testing them against coronaviruses.

If promising drugs are found, investigators plan to try them in an animal infected with the coronavirus perhaps ferrets, because theyre known to get SARS, an illness closely related to Covid-19.

Even if some of these drugs are effective treatments, scientists will still need to make sure they are safe for treating Covid-19. It may turn out, for example, that the dose needed to clear the virus from the body might also lead to dangerous side effects.

This collaboration is far from the only effort to find an antiviral drug effective against the coronavirus. One of the most closely watched efforts involves an antiviral called remdesivir.

In past studies on animals, remdesivir blocked a number of viruses. The drug works by preventing viruses from building new genes.

In February, a team of researchers found that remdesivir could eliminate the coronavirus from infected cells. Since then, five clinical trials have begun to see if the drug will be safe and effective against Covid-19 in people.

Other researchers have taken startling new approaches. On Saturday, Stanford University researchers reported using the gene-editing technology Crispr to destroy coronavirus genes in infected cells.

As the Bay Area went into lockdown on Monday, Dr. Krogan and his colleagues were finishing their map. They are now preparing a report to post online by the end of the week, while also submitting it to a journal for publication.

Their paper will include a list of drugs that the researchers consider prime candidates to treat people ill with the coronavirus.

Whoever is capable of trying them, please try them, Dr. Krogan said.

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Coronavirus Treatment: Hundreds of Scientists Scramble to Find One - The New York Times