A computer image created by Nexu Science Communication together with Trinity College in Dublin, shows a model structurally representative of a betacoronavirus which is the type of virus linked to COVID-19.

Source: NEXU Science Communication | Reuters

Research has gone digital, and medical science is no exception. As the novel coronavirus continues to spread, for instance, scientists searching for a treatment have drafted IBM's Summit supercomputer, the world's most powerful high-performance computing facility, according to the Top500 list, to help find promising candidate drugs.

One way of treating an infection could be with a compound that sticks to a certain part of the virus, disarming it. With tens of thousands of processors spanning an area as large as two tennis courts, the Summit facility at Oak Ridge National Laboratory (ORNL) has more computational power than 1 million top-of-the-line laptops. Using that muscle, researchers digitally simulated how 8,000 different molecules would interact with the virus a Herculean task for your typical personal computer.

"It took us a day or two, whereas it has traditionally taken months on a normal computer," said Jeremy Smith, director of the University of Tennessee/ORNL Center for Molecular Biophysics and principal researcher in the study.

Simulations alone can't prove a treatment will work, but the project was able to identify 77 candidate molecules that other researchers can now test in trials. The fight against the novel coronavirus is just one example of how supercomputers have become an essential part of the process of discovery. The $200 million Summit and similar machines also simulate the birth of the universe, explosions from atomic weapons and a host of events too complicated or too violent to recreate in a lab.

The current generation's formidable power is just a taste of what's to come. Aurora, a $500 million Intel machine currently under installation at Argonne National Laboratory, will herald the long-awaited arrival of "exaflop" facilities capable of a billion billion calculations per second (five times more than Summit) in 2021 with others to follow. China, Japan and the European Union are all expected to switch on similar "exascale" systems in the next five years.

These new machines will enable new discoveries, but only for the select few researchers with the programming know-how required to efficiently marshal their considerable resources. What's more, technological hurdles lead some experts to believe that exascale computing might be the end of the line. For these reasons, scientists are increasingly attempting to harness artificial intelligenceto accomplish more research with less computational power.

"We as an industry have become too captive to building systems that execute the benchmark well without necessarily paying attention to how systems are used," says Dave Turek, vice president of technical computing for IBM Cognitive Systems. He likens high-performance computing record-seeking to focusing on building the world's fastest race car instead of highway-ready minivans. "The ability to inform the classic ways of doing HPC with AI becomes really the innovation wave that's coursing through HPC today."

Just getting to the verge of exascale computing has taken a decade of research and collaboration between the Department of Energy and private vendors. "It's been a journey," says Patricia Damkroger, general manager of Intel's high-performance computing division. "Ten years ago, they said it couldn't be done."

While each system has its own unique architecture, Summit, Aurora, and the upcoming Frontier supercomputer all represent variations on a theme: they harness the immense power of graphical processing units (GPUs) alongside traditional central processing units (CPUs). GPUs can carry out more simultaneous operations than a CPU can, so leaning on these workhorses has let Intel and IBM design machines that would have otherwise required untold megawatts of energy.

IBM's Summit supercomputer currently holds the record for the world's fastest supercomputer.

Source: IBM

That computational power lets Summit, which is known as a "pre-exascale" computer because it runs at 0.2 exaflops, simulate one single supernova explosion in about two months, according to Bronson Messer, the acting director of science for the Oak Ridge Leadership Computing Facility. He hopes that machines like Aurora (1 exaflop) and the upcoming Frontier supercomputer (1.5 exaflops) will get that time down to about a week. Damkroger looks forward to medical applications. Where current supercomputers can digitally model a single heart, for instance, exascale machines will be able to simulate how the heart works together with blood vessels, she predicts.

But even as exascale developers take a victory lap, they know that two challenges mean the add-more-GPUs formula is likely approaching a plateau in its scientific usefulness. First, GPUs are strong but dumbbest suited to simple operations such as arithmetic and geometric calculations that they can crowdsource among their many components. Researchers have written simulations to run on flexible CPUs for decades and shifting to GPUs often requires starting from scratch.

GPU's have thousands of cores for simultaneous computation, but each handles simple instructions.

Source: IBM

"The real issue that we're wrestling with at this point is how do we move our code over" from running on CPUs to running on GPUs, says Richard Loft, a computational scientist at the National Center for Atmospheric Research, home of Top500's 44th ranking supercomputerCheyenne, a CPU-based machine "It's labor intensive, and they're difficult to program."

Second, the more processors a machine has, the harder it is to coordinate the sharing of calculations. For the climate modeling that Loft does, machines with more processors better answer questions like "what is the chance of a once-in-a-millennium deluge," because they can run more identical simulations simultaneously and build up more robust statistics. But they don't ultimately enable the climate models themselves to get much more sophisticated.

For that, the actual processors have to get faster, a feat that bumps up against what's physically possible. Faster processors need smaller transistors, and current transistors measure about 7 nanometers. Companies might be able to shrink that size, Turek says, but only to a point. "You can't get to zero [nanometers]," he says. "You have to invoke other kinds of approaches."

If supercomputers can't get much more powerful, researchers will have to get smarter about how they use the facilities. Traditional computing is often an exercise in brute forcing a problem, and machine learning techniques may allow researchers to approach complex calculations with more finesse.

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Take drug design. A pharmacist considering a dozen ingredients faces countless possible recipes, varying amounts of each compound, which could take a supercomputer years to simulate. An emerging machine learning technique known as Bayesian Optimization asks, does the computer really need to check every single option? Rather than systematically sweeping the field, the method helps isolate the most promising drugs by implementing common-sense assumptions. Once it finds one reasonably effective solution, for instance, it might prioritize seeking small improvements with minor tweaks.

In trial-and-error fields like materials science and cosmetics, Turek says that this strategy can reduce the number of simulations needed by 70% to 90%. Recently, for instance, the technique has led to breakthroughs in battery design and the discovery of a new antibiotic.

Fields like climate science and particle physics use brute-force computation in a different way, by starting with simple mathematical laws of nature and calculating the behavior of complex systems. Climate models, for instance, try to predict how air currents conspire with forests, cities, and oceans to determine global temperature.

Mike Pritchard, a climatologist at the University of California, Irvine, hopes to figure out how clouds fit into this picture, but most current climate models are blind to features smaller than a few dozen miles wide. Crunching the numbers for a worldwide layer of clouds, which might be just a couple hundred feet tall, simply requires more mathematical brawn than any supercomputer can deliver.

Unless the computer understands how clouds interact better than we do, that is. Pritchard is one of many climatologists experimenting with training neural networksa machine learning technique that looks for patterns by trial and errorto mimic cloud behavior. This approach takes a lot of computing power up front to generate realistic clouds for the neural network to imitate. But once the network has learned how to produce plausible cloudlike behavior, it can replace the computationally intensive laws of nature in the global model, at least in theory. "It's a very exciting time," Pritchard says. "It could be totally revolutionary, if it's credible."

Companies are preparing their machines so researchers like Pritchard can take full advantage of the computational tools they're developing. Turek says IBM is focusing on designing AI-ready machines capable of extreme multitasking and quickly shuttling around huge quantities of information, and the Department of Energy contract for Aurora is Intel's first that specifies a benchmark for certain AI applications, according to Damkroger. Intel is also developing an open-source software toolkit called oneAPI that will make it easier for developers to create programs that run efficiently on a variety of processors, including CPUs and GPUs.As exascale and machine learning tools become increasingly available, scientists hope they'll be able to move past the computer engineering and focus on making new discoveries. "When we get to exascale that's only going to be half the story," Messer says. "What we actually accomplish at the exascale will be what matters."

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Next-gen supercomputers are fast-tracking treatments for the coronavirus in a race against time - CNBC

In the race to develop a treatment for the rapidly spreading illness Covid-19, dozens of drugs are being tested around the world. Its an urgent mission because the latest data suggests that some 20 percent of people infected have serious illness, and around 1 percent may die.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told Congress on Wednesday that Covid-19 is 10 times more lethal than the seasonal flu.

The danger stems from the pathogen itself: a virus called SARS-CoV-2.

Teeny tiny viruses are one of the biggest threats that humanity has ever faced. They are behind some of the most devastating pandemics ever known. Even with all of modern medicine, we have only eradicated one virus, smallpox, which required a decades-long global mass vaccination effort.

SARS-CoV-2, the brand new foe, is spreading fast even as entire countries, like Italy, are locking down to prevent its transmission. Estimates of its potential impact vary, but Brian Monahan, the attending physician of the US Congress, told lawmakers Wednesday he expects between 70 million and 150 million people in the US to get infected with the virus over time.

Right now, doctors are using general treatment measures to control the symptoms of Covid-19, but theres not yet a specific vaccine or cure.

Several factors make viruses like SARS-CoV-2 a particularly pernicious threat to humans. The good news is scientists have learned more about how they attack. Theyve also come up with ways to keep some of the deadliest of these tiny germs in check and are slowly inching toward cures. The question now is whether that research will bear fruit in time to blunt the blow of the Covid-19 pandemic and help us get ahead of the next outbreak.

Viruses are the most bizarre germs. Using just a handful of molecules, they assemble into all kinds of tiny shapes, and with just a small set of instructions, they can wreak havoc across entire ecosystems and threaten crop harvests. They can travel between hosts through the air, water, soil, and droplets. They mutate rapidly. And they are truly everywhere, from the oceans to the skies.

Compared to infectious agents like bacteria and fungi, viruses are much smaller and simpler. In fact, viruses can even make other germs sick. Yet theyre so simple that most scientists dont even consider them to be living organisms.

For instance, the poliovirus is just 30 nanometers wide. The SARS-CoV-2 virus behind Covid-19 is about 120 nanometers. Meanwhile, the E. coli bacterium is more than 16 times larger than SARS-CoV-2, and the human red blood cell is 64 times larger. A human cell uses 20,000 different types of proteins. HIV uses just 15. SARS-CoV-2 uses 33.

With all that extra space, larger pathogens like bacteria store the molecular tools they need to make copies of themselves and to fight off infections of their own. These tools are also what make bacteria vulnerable to antibiotics, drugs that interfere with molecular mechanisms in bacteria but not those of human cells, so they have a targeted effect.

But antibiotics dont work on viruses. Thats because viruses dont reproduce on their own. Rather, they invade cells and hijack their hosts machinery to make copies of themselves.

Bacteria are very different from us, so theres a lot of different targets for drugs. Viruses replicate in cells, so they use a lot of the same mechanisms that our cells do, said Diane Griffin, a professor of microbiology and immunology at the Bloomberg School of Public Health at Johns Hopkins University. So its been harder to find drugs that target the virus but dont damage the cell as well.

Theres also a huge variety of viruses, and they mutate quickly, so tailored treatments and vaccines against a virus can lose effectiveness over time.

Another factor that makes viruses so difficult to treat is how our bodies respond to them. Once the immune system detects a virus, it makes antibodies. These are proteins that attach to a virus or a virus-infected cell, marking it for destruction or preventing it from infecting new cells.

The problem is that a virus can cause a lot of damage and infect other people before the immune system readies its defenses. When those defenses kick in, they can cause other problems like fever and inflammation. And by the time these symptoms show up, the virus may already be in decline, or it may be too late to act.

Often at the time that virus diseases present themselves, its fairly far into the replication of that virus in that person, Griffin said. Many symptoms of the virus disease are actually manifestations of the immune response to the disease, so often things are sort of starting to get better at the time that you actually even figure out somebody has a virus infection.

Researchers use two broad strategies to combat viral infections: slowing down the damage from the virus, and speeding up and strengthening the bodys countermeasures.

Antiviral drugs are one approach to slowing down viruses. Like antibiotics, these are drugs that hamper the virus without causing much collateral damage. The majority of antivirals are targeting the viruses [themselves]. That means the components of the viruses, the viral enzymes, the surface proteins, said Pei-Yong Shi, a biochemistry and molecular biology professor at the University of Texas Medical Branch. By attacking different parts of the virus, antiviral compounds can prevent a virus from entering cells or they can interfere with its reproduction.

For example, remdesivir, under development by Gilead Sciences, is being studied as a way to treat Covid-19. It works by blocking the SARS-CoV-2 virus from copying its genetic material, RNA, the instructions the virus uses to replicate itself. Remdesivir resembles a component of RNA, but when its taken up by the virus, it causes the copying process to stop. Crucially, remdesivir fools the virus, but not human cells.

Protease inhibitors are another class of antiviral drugs, like lopinavir and ritonavir used to treat HIV (the -vir suffix is used to denote an antiviral drug, similar to how -cillin denotes an antibiotic). These compounds block an enzyme in the virus that normally trims proteins down, allowing the virus to infect other cells. When the enzyme is blocked, the virus doesnt mature properly, rendering it inert.

Researchers are also studying how to use antibodies to a given virus collected from engineered animals or from people previously infected with the same virus. By administering antibodies as a treatment, the recipients immune system can get a head start on identifying and eliminating the viral threat rather than waiting to build up its own antibodies.

There are also drugs like interferons that trigger a general immune response. These are a series of signaling molecules that make cells in the body more resistant to infection, inhibiting the spread of a virus while the rest of the immune system catches up. Its mainly used to control persistent infections like hepatitis B.

But interferons can have severe side effects like inflammation, so it requires fine-tuning to treat a virus without doing more harm than good. Doctors have used interferon with other antiviral drugs to treat Covid-19 in China and researchers are investigating this approach as another potential therapy.

Doctors can also use a number of different therapies to limit the immune systems response to viruses, like fever and inflammation, which can sometimes cause more damage to a patient than the virus itself. Anti-inflammatory drugs like corticosteroids and chloroquine are often used to lessen these symptoms.

And there are also vaccines for some viruses and efforts to develop new ones. These are treatments that coach the immune system to detect and fight off a virus before an infection takes place. These are powerful tools for controlling viruses across an entire population, but theyre tricky to optimize for a rapidly changing pathogen, and they require extensive, time-consuming testing to ensure they are safe for a wide segment of the population.

However, even if effective treatments enter the market, the virus will likely remain a threat. As weve learned with influenza (another respiratory disease caused by viruses), despite updated vaccines, new treatments, and a long history of public health responses, there are still between 12,000 and 60,000 flu deaths each year in the US. Covid-19 could remain a persistent threat, too.

To be clear, the best way to fight a virus is to prevent infections in the first place. And that depends on public health measures during an outbreak, like quarantines and social distancing, as well as personal tactics like robust, 20-second hand-washing with soap.

While there is a large and growing body of research on drugs to control viruses, they are still few and far between. We dont have that many antiviral drugs for acute infections, Griffin said. You often dont have any choice except to let it run its course.

Developing new drugs can take years of testing, and by then, an outbreak may have faded, or another more threatening pathogen may have emerged. Even viruses for which we do have antiviral drugs, like influenza, the illness often isnt detected in time to make it worth the treatment.

Other viruses like HIV can be controlled with drugs, but not eliminated, as hidden reservoirs of the virus remain in the body.

And within a population, there are always people who are more susceptible to infections, like people with depressed immune systems. For them, treatments and vaccines may not work, so they depend on the people around them to be immunized and to take proper infection control procedures.

All of which brings us back to prevention as the most effective way to combat viruses within a population. That means global coordinated action can be one of the best strategies to control the smallest pathogens. And simple tools like soap and water can be more effective at fighting a pandemic than the best drugs.

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Is there a cure for coronavirus? Why Covid-19 is so hard to treat - Vox.com

Henry Ford Health System plans to rapidly expand its life-extending precision medicine program in Detroit after the Jeffries family pledged $25 million to create a specialized center.

The $25 million donation, provided by developer Chris Jeffries and his wife, Lisa, is the largest single gift from individuals in Henry Ford's 105-year history and one of the largest in the nation for a precision medicine program, Henry Ford officials said.

"We are incredibly grateful to Lisa and Chris Jeffries for their generosity," Wright Lassiter III, president and CEO of Henry Ford Health System, said in a statement. "We are experiencing a momentous era in medicine, a radical shift from the traditional approach to cancer care. This gift will help us consolidate and advance our collective efforts to create unprecedented access to advanced, highly personalized treatments for our patients and members."

But in the past three months, precision medicine or precision health, as neurosurgeon Steven Kalkanis, M.D., CEO of the Henry Ford Medical Group, likes to call it is now available for a whole host of new treatments besides those for cancer.

"Hot off the press. There have been animal studies and now clinical studies, only in the last several months, where precision health is ready for prime time and for human beings," said Kalkanis, who also is Henry Ford's chief academic officer.

Over the past decade, precision medicine has been evolving as a new type of medical care that initially focused on treating patients with various forms of cancer, including brain, lung, colon and pancreatic. It works like this: By analyzing patients' own molecular profile and the genetic mutations of their tumors, doctors are able to use the information to develop personalized treatments that could be more effective than standard care.

Doctors are now using precision medicine approaches to treat many other conditions, including cystic fibrosis, asthma, depression, heart disease, autoimmune diseases and multiple sclerosis, Kalkanis said.

"We have a whole era opening up to treat a host of other chronic diseases, using precision medicine to identify patients' molecular profiles, but potentially using existing drugs for everything from asthma to high blood pressure to depression," Kalkanis said. "However, the majority (of precision medicine) is still about designing a tailored drug regimen for individual patients."

Kalkanis said patients with some chronic conditions will one day soon be able to take a blood test and have their molecular profile entered into a database of existing drugs that may be able to match to an existing drug or to new ones being created in real time.

"We have found, in one of our clinical trials, that a (patient had a) rare type of brain cancer with a mutation impacting glucose levels. We used an existing diabetes drug and the patient went into remission," Kalkanis said.

Why the Jeffries donated

Chris Jeffries' father, Gerald was diagnosed with a highly malignant brain tumor in 2001.

Treated initially by neuro-oncologist Tom Mikkelsen and later Kalkanis and the Hermelin Brain Tumor Center team, Gerald was given only nine to 11 months to live, but using a precision medicine approach, he lived another five years until he died in December 2006.

"That meant so much to us. It's impossible to describe," Chris Jeffries said in a statement. Lisa Jeffries also lost her stepfather to cancer.

A native of Flint, Chris Jeffries is co-founder of Millennium Partners, a real estate development company that specializes in mixed-use, urban living and entertainment centers in Boston; San Francisco; Miami; Washington D.C.; Los Angeles; and New York.

Last year, the Jeffries donated $33 million to the University of Michigan Law School, where Chris was a 1974 graduate. The donation is earmarked for student support, including scholarships and other forms of financial aid, summer funding programs, and debt management. It was the largest private donation to the law school in its history, UM said.

Kalkanis said Gerald Jeffries was one of the first cohorts of patients in Henry Ford's personalized medicine program long before it was called precision medicine, in the early 2000s.

"He was enrolled in a clinical trial at Henry Ford 10 to 15 years ago and treated with a novel drug based on his unique cancer characteristics," Kalkanis said. "Because of that, he lived way beyond his life expectancy. The family was very supportive of our program and especially wanted to provide this same hope to others once they learned of the enhanced capability of precision medicine."

Since Gerald Jeffries was treated and Henry Ford developed its precision medicine approach, Kalkanis said there have been a number of patients who have outlived their prognoses. He said doctors can now give patients and families more hope than ever.

"We went through the precision medicine protocol, based on his own unique biomarkers and using a novel drug," he said. "Today these tests have become much more accessible. (For instance), a decade ago, it cost $5,000 (for testing). Now it costs several hundred for the tests" that can lead to the novel, personalized treatment.

Henry Ford's precision medicine program

For years, Henry Ford has been at the forefront of the precision medicine revolution, making world-class, targeted cancer treatments available at its national destination referral center, the Henry Ford Cancer Institute, officials said.

"By analyzing genetic and non-genetic factors, we can gain a better understanding of how a disease forms, progresses and can be treated in a specific patient," Mikkelsen, who is Henry Ford's medical director of the Precision Medicine Program and Clinical Trials Office, said in a statement.

"As of now, we can check for more than 500 genomic markers, which helps us understand the pattern of changes in a patient's tumor cells that influence how cancer grows and spreads," Mikkelsen said. "I'm confident this gift will lead to advancements that provide hope for patients with even the most complex diagnoses."

Kalkanis said the $25 million donation, which is expected to be received over the next several years, will enable Henry Ford to do a number of things.

"It takes investment to build out our biodepository with tissue samples, test them, look for biomarkers and see if (patients are) eligible for certain drugs," Kalkanis said. "We need to design our lab platform that is FDA-approved and recruit the best and brightest scientists and clinicians (specializing in) other cancer types."

Based on the current projection of about four to five chronic diseases and about 10 subspecialties that can be addressed by precision medicine, Kalkanis estimated Henry Ford will recruit two to three scientists and clinicians each year for the next few years.

"We are launching the search process for key researchers and working with the lab and pathology group for tests this calendar year," he said. "We should be up and running over the next year."

Adnan Munkarah, M.D., Henry Ford's executive vice president and chief clinical officer, said taking research in the lab and translating it to patient care is a standard process at Henry Ford.

"(It) is a critical element to help us treat many of the most challenging conditions our patients face," Munkarah said in a statement. "Translational research is bench-to-bedside, meaning it allows patients to benefit from discoveries in real time. That is an essential part of our history and commitment to medicine and academics not only offering the latest innovations in medicine, but also playing a leading role in their development."

Precision medicine is an approach to patient care that allows doctors to select treatments most likely to help patients based on a genetic understanding of their disease.

"The support of our donors is the fuel behind our clinical innovations and the breakthroughs that are improving people's lives," Mary Jane Vogt, Henry Ford's senior vice president and chief development officer, said in a statement. "It is remarkable to work with donors who believe in a better tomorrow and the power of a unified approach to medicine."

The Jeffrieses said they believe Henry Ford will achieve transformational advancements in cancer treatment using precision medicine and personalized treatments.

"The team at Henry Ford is second to none," said Chris Jeffries. "We believe this gift will lead to other families having more time together, as I had with my father. Defeating cancer requires a concerted effort from everyone and we hope to make as big an impact on that goal as possible."

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Henry Ford to expand precision medicine program with help of $25 million donation - ModernHealthcare.com

Interested participants have until 27 April 2020 to submit abstracts for the IAEA International Conference on Molecular Imaging and Clinical PETCT (IPET-2020), to be held in Vienna, Austria, from 23 November to 27 November 2020.

The conference will focus on theranostics, a patient-centred and personalized form of care, coupling diagnostics and therapy, which enables medical professionals to focus on the specific needs of individual patients.

The meeting, in which participation is free, will include presentations as well as interactive sessions and free discussions with top experts in the field. Participants will be able to earn continuing medical education (CME) credits, and virtual attendees can officially register to the livestream and take brief quizzes using the conference app after individual sessions to earn some CME credits too. Up to 100 conference abstracts will be published on the conference webpage on iaea.org.

IPET-2020 will focus on theranostics which is a major topic in global health that allows us to provide personalized care tailored to the specific needs of the patient, said Diana Paez, Head of the Nuclear Medicine and Diagnostic Imaging Section at the IAEA. Participants will have the opportunity to attend in person, as well as virtually, to learn about advances in the field, the challenges faced by countries to address theranostic applications and future developments and trends.

IPET-2020 is the fourth conference of its kind; it follows three earlier conferences organized by the IAEA in 2007, 2011 and 2015. It will bring together about 500 nuclear medicine physicians, radiologists, oncologists and medical physicists from around the world. It will be a unique chance for nuclear medicine physicians and scientists working in all aspects of molecular imaging to showcase their research and create lasting connections with their colleagues from all over the globe, Paez said.

IPET-2020 provides a unique platform for professionals in medical imaging to come together and exchange experiences from their clinical work and learn how things are being done in different countries since theranostics is a field that is rapidly evolving and increasingly relevant for all of us globally, said Stefano Fanti, Director of the Nuclear Medicine Division at the St. Orsola-MalpighiUniversity Hospital in Bologna and lecturer for IPET-2020.

In addition to its focus on theranostic applications, IPET-2020 will cover the latest developments in imaging devices, radiopharmaceuticals and radio-guided surgery. Special sessions on ethics and leadership will provide an opportunity for participants to learn about the tools needed to prepare themselves for leadership in their respective professions.

An exhibition, where companies and professional organizations will be demonstrating their cutting-edge technologies, will take place alongside the sessions of the conference.

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Call for Papers: International Conference on Molecular Imaging and Clinical PETCT in November - International Atomic Energy Agency

LYON, France and CAMBRIDGE, Mass. , March 16, 2020 (GLOBE NEWSWIRE) -- ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, today announced the appointment of Melanie Rolli, M.D., to its Board of Directors and the intention to propose the ratification of her appointment at ERYTECHs next General Meeting of Shareholders. Dr. Rolli has more than 15 years of experience in the global biopharmaceutical and biotechnology industry, including in both Europe and the United States. Dr. Rollis appointment follows the resignation of Allene Diaz, who resigned from the Board effective September 30, 2019.

We are very pleased to welcome Melanie to our Board of Directors, commented Dr Jean-Paul Kress, Chairman of the Board of ERYTECH Pharma.We look forward to working with her to develop ERYTECHs business plans and strategy as ERYTECH advances its late-stage clinical programs and begins preparations for its transition into a commercial-stage company.

I am delighted to be joining ERYTECHs Board of Directors, said Dr. Rolli. It is an exciting time for ERYTECH as its lead product eryaspase is progressing through a pivotal Phase 3 clinical trial in one of the largest unmet medical needs in oncology. I look forward to working closely with the Board and leadership team in supporting the Companys plans.

Dr. Rolli currently serves as the Chief Executive Officer of PIQUR Therapeutics AG, a Basel, Switzerland-based clinical stage biotechology company dedicated to drug development of targeted therapies in various oncological and dermatological indications. Previously, she was at Novartis Pharmaceuticals AG for 14 years, where she held positions of increasing responsibilities across the Drug Development, Safety, and Medical Affairs functions. At Novartis, she spent eight years in the United States in global and local positions as the Medical Director in Primary Care, Respiratory, Womens Health and Dermatology and Oncology franchises.

Prior to joining Novartis, she worked as a post-doctoral cancer research physician at SCRIPPS Research Institute for Molecular and Experimental Medicine in La Jolla, California, and as a clinicial and researcher in Germany.

Dr. Rolli graduated from the University of Heidelberg with a doctorate in medicine and pharmacology.

About ERYTECH and eryaspase: http://www.erytech.com

ERYTECH is a clinical-stage biopharmaceutical company developing innovative red blood cell-based therapeutics for severe forms of cancer and orphan diseases. Leveraging its proprietary ERYCAPS platform, which uses a novel technology to encapsulate drug substances inside red blood cells, ERYTECH is developing a pipeline of product candidates for patients with high unmet medical needs. ERYTECHs primary focus is on the development of product candidates that target the altered metabolism of cancer cells by depriving them of amino acids necessary for their growth and survival.

The Companys lead product candidate, eryaspase, which consists of L-asparaginase encapsulated inside donor-derived red blood cells, targets the cancer cells altered asparagine and glutamine metabolism. Eryaspase is in Phase 3 clinical development for the treatment of second-line pancreatic cancer and in Phase 2 for the treatment of first-line triple-negative breast cancer. An investigator-sponsored Phase 2 study in second-line acute lymphoblastic leukemia is ongoing in the Nordic countries of Europe.

ERYTECH produces its product candidates for treatment of patients in Europe at its GMP-approved manufacturing site inLyon, France, and for patients in the United States at its recently opened GMP manufacturing site in Princeton, New Jersey, USA.

ERYTECH is listed on the Nasdaq Global Select Market inthe United States(ticker: ERYP) and on theEuronext regulated market inParis(ISIN code: FR0011471135, ticker: ERYP). ERYTECH is part of the CACHealthcare, CAC Pharma & Bio, CAC Mid & Small, CAC All Tradable, EnterNext PEA-PME 150 and Next Biotech indexes.

Forward-looking information

This press release contains forward-looking statements with respect to the clinical development plans of eryaspase, including ERYTECHs plans for transition into a commercial-stage company. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, believes, anticipates, expects, intends, plans, seeks, estimates, may, will and continue and similar expressions. All statements contained in this press release other than statements of historical facts are forward-looking statements, including, without limitation, statements regarding the ERYTECHs business strategy including its clinical development of eryaspase; the status of the TRYbeCA1 trial including the timeline for patient enrollment, expansion of trial into the United States and intended activities with respect to the interim analysis; the potential of ERYTECHs product pipeline; the timing of ERYTECHs preclinical studies and clinical trials and announcements of data from those studies and trials; ERYTECHs anticipated manufacturing capacity and ability to meet future demand and ERYTECHs anticipated cash runway and sufficiency of cash resources. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond ERYTECH's control. There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Further description of these risks, uncertainties and other risks can be found in the Companys regulatory filings with the French Autorit des Marchs Financiers (AMF), the Companys Securities and Exchange Commission (SEC) filings and reports, including in the Companys 2018 Document de Rfrence filed with the AMF in March 2019 and in the Companys Annual Report on Form 20-F filed with the SEC on March 29, 2019 and future filings and reports by the Company. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements. ERYTECH disclaims any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in ERYTECHs expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based, except to the extent required by law.

CONTACTS

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ERYTECH Announces the Appointment of Dr. Melanie Rolli to its Board of Directors - GlobeNewswire

Mar 12th 2020

BEING ABLE to see all the details of the genome at once necessarily makes medicine personal. It can also make it precise. Examining illness molecule by molecule allows pharmaceutical researchers to understand the pathways through which cells act according to the dictates of genes and environment, thus seeing deep into the mechanisms by which diseases cause harm, and finding new workings to target. The flip side of this deeper understanding is that precision brings complexity. This is seen most clearly in cancer. Once, cancers were identified by cell and tissue type. Now they are increasingly distinguished by their specific genotype that reveals which of the panoply of genes that can make a cell cancerous have gone wrong in this one. As drugs targeted against those different mutations have multiplied, so have the options for oncologists to combine them to fit their patients needs.

Cancer treatment has been the most obvious beneficiary of the genomic revolution but other diseases, including many in neurology, are set to benefit, too. Some scientists now think there are five different types of diabetes rather than two. There is an active debate about whether Parkinsons is one disease that varies a lot, or four. Understanding this molecular variation is vital when developing treatments. A drug that works well on one subtype of a disease might fail in a trial that includes patients with another subtype against which it does not work at all.

Thus how a doctor treats a disease depends increasingly on which version of the disease the patient has. The Personalised Medicine Coalition, a non-profit advocacy group, examines new drugs approved in America to see whether they require such insights in order to be used. In 2014, it found that so-called personalised medicines made up 21% of the drugs newly approved for use by Americas Food and Drug Administration (FDA). In 2018 the proportion was twice that.

Two of those cited were particularly interesting: Vitrakvi (larotrectinib), developed by Loxo Oncology, a biotech firm, and Onpattro (patisiran), developed by Alnylam Pharmaceuticals. Vitrakvi is the first to be approved from the start as tumour agnostic: it can be used against any cancer that displays the mutant protein it targets. Onpattro, which is used to treat peripheral-nerve damage, is the first of a new class of drugssmall interfering RNAs, or siRNAsto be approved. Like antisense oligonucleotides (ASOs), siRNAs are little stretches of nucleic acid that stop proteins from being made, though they use a different mechanism.

Again like ASOs, siRNAs allow you to target aspects of a disease that are beyond the reach of customary drugs. Until recently, drugs were either small molecules made with industrial chemistry or bigger ones made with biologynormally with genetically engineered cells. If they had any high level of specificity, it was against the actions of a particular protein, or class of proteins. Like other new techniques, including gene therapies and anti-sense drugs, siRNAs allow the problem to be tackled further upstream, before there is any protein to cause a problem.

Take the drugs that target the liver enzyme PCSK9. This has a role in maintaining levels of bad cholesterol in the blood; it is the protein that was discovered through studies of families in which congenitally high cholesterol levels led to lots of heart attacks. The first generation of such drugs were antibodies that stuck to the enzyme and stopped it working. However, the Medicines Company, a biotech firm recently acquired by Novartis, won approval last year for an siRNA called inclisiran that interferes with the expression of the gene PCSK9thus stopping the pesky protein from being made in the first place. Inclisiran needs to be injected only twice a year, rather than once a month, as antibodies do.

New biological insights, new ways of analysing patients and their disease and new forms of drug are thus opening up a wide range of therapeutic possibilities. Unfortunately, that does not equate to a range of new profitable opportunities.

Thanks in part to ever better diagnosis, there are now 7,000 conditions recognised as rare diseases in America, meaning that the number of potential patients is less than 200,000. More than 90% of these diseases have no approved treatment. These are the diseases that personalised, precision medicine most often goes after. Nearly 60% of the personalised medicines approved by the FDA in 2018 were for rare diseases.

Zolgensma is the most expensive drug ever brought to market.

That might be fine, were the number of diseases stable. But precision in diagnosis is increasingly turning what used to be single diseases into sets of similar-looking ones brought about by distinctly different mechanisms, and thus needing different treatment. And new diseases are still being discovered. Medical progress could, in short, produce more new diseases than new drugs, increasing unmet need.

Some of it will, eventually, be met. For one thing, there are government incentives in America and Europe for the development of drugs for rare diseases. And, especially in America, drugs for rare diseases have long been able to command premium prices. Were this not the case, Novartis would not have paid $8.7bn last year to buy AveXis, a small biotech firm, thereby acquiring Zolgensma, a gene therapy for spinal muscular atrophy (SMA). Most people with SMA lack a working copy of a gene, SMN1, which the nerve cells that control the bodys muscles need to survive. Zolgensma uses an empty virus-like particle that recognises nerve cells to deliver working copies of the gene to where it is needed. Priced at $2.1m per patient, it is the most expensive drug ever brought to market. That dubious accolade might not last long. BioMarin, another biotech firm, is considering charging as much as $3m for a forthcoming gene therapy for haemophilia.

Drug firms say such treatments are economically worthwhile over the lifetime of the patient. Four-fifths of children with the worst form of SMA die before they are four. If, as is hoped, Zolgensma is a lasting cure, then its high cost should be set against a half-century or more of life. About 200 patients had been treated in America by the end of 2019.

But if some treatments for rare diseases may turn a profit, not all will. There are some 6,000 children with SMA in America. There are fewer than ten with Jansens disease. When Dr Nizar asked companies to help develop a treatment for it, she says she was told your disease is not impactful. She wrote down the negative responses to motivate herself: Every day I need to remind myself that this is bullshit.

A world in which markets shrink, drug development gets costlier and new unmet needs are ceaselessly discovered is a long way from the utopian future envisaged by the governments and charities that paid for the sequencing of all those genomes and the establishment of the worlds biobanks. As Peter Bach, director of the Centre for Health Policy and Outcomes, an academic centre in New York, puts it with a degree of understatement: if the world needs to spend as much to develop a drug for 2,000 people as it used to spend developing one for 100,000, the population-level returns from medical research are sharply diminishing.

And it is not as if the costs of drug development have been constant. They have gone up. What Jack Scannell, a consultant and former pharmaceutical analyst at UBS, a bank, has dubbed Erooms lawEroom being Moore, backwardsshows the number of drugs developed for a given amount of R&D spending has fallen inexorably, even as the amount of biological research skyrocketed. Each generation assumes that advances in science will make drugs easier to discover; each generation duly advances science; each generation learns it was wrong.

For evidence, look at the way the arrival of genomics in the 1990s lowered productivity in drug discovery. A paper in Nature Reviews Drug Discovery by Sarah Duggers from Columbia University and colleagues argues that it brought a wealth of new leads that were difficult to prioritise. Spending rose to accommodate this boom; attrition rates for drugs in development subsequently rose because the candidates were not, in general, all that good.

Today, enthused by their big-science experience with the genome and enabled by new tools, biomedical researchers are working on exhaustive studies of all sorts of other omes, including proteomesall the proteins in a cell or body; microbiomesthe non-pathogenic bacteria living in the mouth, gut, skin and such; metabolomessnapshots of all the small molecules being built up and broken down in the body; and connectomes, which list all the links in a nervous system. The patterns they find will doubtless produce new discoveries. But they will not necessarily, in the short term, produce the sort of clear mechanistic understanding which helps create great new drugs. As Dr Scannell puts it: We have treated the diseases with good experimental models. Whats left are diseases where experiments dont replicate people. Data alone canot solve the problem.

Daphne Koller, boss of Insitro, a biotech company based in San Francisco, shares Dr Scannells scepticism about the way drug discovery has been done. A lot of candidate drugs fail, she says, because they aim for targets that are not actually relevant to the biology of the condition involved. Instead researchers make decisions based on accepted rules of thumb, gut instincts or a ridiculous mouse model that has nothing to do with what is actually going on in the relevant human diseaseeven if it makes a mouse look poorly in a similar sort of way.

But she also thinks that is changing. Among the things precision biology has improved over the past five to 10 years have been the scientists own tools. Gene-editing technologies allow genes to be changed in various ways, including letter by letter; single-cell analysis allows the results to be looked at as they unfold. These edited cells may be much more predictive of the effects of drugs than previous surrogates. Organoidsself-organised, three-dimensional tissue cultures grown from human stem cellsoffer simplified but replicable versions of the brain, pancreas, lung and other parts of the body in which to model diseases and their cures.

Insitro is editing changes into stem cellswhich can grow into any other tissueand tracking the tissues they grow into. By measuring differences in the development of very well characterised cells which differ in precisely known ways the company hopes to build more accurate models of disease in living cells. All this work is automated, and carried out on such a large scale that Dr Koller anticipates collecting many petabytes of data before using machine learning to make sense of it. She hopes to create what Dr Scannell complains biology lacks and what drug designers need: predictive models of how genetic changes drive functional changes.

There are also reasons to hope that the new upstream drugsASOs, siRNAs, perhaps even some gene therapiesmight have advantages over todays therapies when it comes to small-batch manufacture. It may also prove possible to streamline much of the testing that such drugs go through. Virus-based gene-therapy vectors and antisense drugs are basically platforms from which to deliver little bits of sequence data. Within some constraints, a platform already approved for carrying one message might be fast-tracked through various safety tests when it carries another.

One more reason for optimism is that drugs developed around a known molecule that marks out a diseasea molecular markerappear to be more successful in trials. The approval process for cancer therapies aimed at the markers of specific mutations is often much shorter now than it used to be. Tagrisso (osimertinib), an incredibly specialised drug, targets a mutation known to occur only in patients already treated for lung cancer with an older drug. Being able to specify the patients who stand to benefit with this degree of accuracy allows trials to be smaller and quicker. Tagrisso was approved less than two years and nine months after the first dose was given to a patient.

With efforts to improve the validity of models of disease and validate drug targets accurately gaining ground, Dr Scannell says he is sympathetic to the proposal that, this time, scientific innovation might improve productivity. Recent years have seen hints that Erooms law is being bent, if not yet broken.

If pharmaceutical companies do not make good on the promise of these new approaches then charities are likely to step in, as they have with various ASO treatments for inherited diseases. And they will not be shackled to business models that see the purpose of medicine as making drugs. The Gates Foundation and Americas National Institutes of Health are investing $200m towards developing treatments based on rewriting genes that could be used to tackle sickle-cell disease and HIVtreatments that have to meet the proviso of being useful in poor-country clinics. Therapies in which cells are taken out of the body, treated in some way and returned might be the basis of a new sort of business, one based around the ability to make small machines that treat individuals by the bedside rather than factories which produce drugs in bulk.

There is room in all this for individuals with vision; there is also room for luck: Dr Nizar has both. Her problem lies in PTH1R, a hormone receptor; her PTH1R gene makes a form of it which is jammed in the on position. This means her cells are constantly doing what they would normally do only if told to by the relevant hormone. A few years ago she learned that a drug which might turn the mutant receptor off (or at least down a bit) had already been characterisedbut had not seemed worth developing.

The rabbit, it is said, outruns the fox because the fox is merely running for its dinner, while the rabbit is running for its life. Dr Nizars incentives outstrip those of drug companies in a similar way. By working with the FDA, the NIH and Massachusetts General Hospital, Dr Nizar helped get a grant to make enough of the drug for toxicology studies. She will take it herself, in the first human trial, in about a years time. After that, if things go well, her childrens pain may finally be eased.

This article appeared in the Technology Quarterly section of the print edition under the headline "Kill or cure?"

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New drugs are costly and unmet need is growing - The Economist

Undergraduate students in the biological sciences honors program were informed on Wednesday afternoon that they will officially not be allowed to work in laboratories starting March 28, the deadline the University set after which all classes must be held online.

As a part of the honors program, students conduct novel, independent research and then write a formal honors thesis in a specific field of study. As a result of the disruption, participants should plan to collect as much data as possible before spring break, according to an email sent by Laura Schoenle, coordinator of undergraduate research and honors.

Even though aspects of the course will be cut short, students enrolled in Biology 4990: Independent Research in Biology, will receive full credit.

If you are enrolled in BIOG 4990, you will be able to receive full credit for the course, as we will have passed the 60% time point in the semester when we reach spring break, Schoenle wrote in an email to biological sciences honors students.

The decision was made in line with the Department of Educations guidelines for assigning credit in case of a disruption in instruction.

Although students living in off-campus housing may be inclined to continue working on their research projects, Cornell has discouraged working in research labs after March 27.

I was informed yesterday that Cornell does not want undergrads to continue working in research labs after March 27 even if you are living in off-campus housing and you plan to stay here in Ithaca, said Scott D. Emr, director of the Weill Institute for Cell and Molecular Biology, in an email to Weill Institute undergraduate students.

After March 27, honors students are encouraged to work with their laboratory research mentors to continue any data analysis and finish their theses remotely. The timeline for the program will remain the same, with students expected to submit their final papers to their group leader and committee for review by mid-April.

However, honors poster sessions to be held in May have been cancelled and the presentation requirement for honors will also be waived, according to Scheonle.

I realize these are challenging and stressful times. Please know that the entire university community, including the Bio Sci Honors Committee, has your best interests at heart, and respects the great efforts honors students put towards their research, Scheonle wrote.

The change in honors thesis policies sparked a variety of responses from students.

Natalie Brown 20, a Biology and Society major, works in Prof. Minglin Mas lab, biological and environmental engineering, pursuing an honors thesis project that investigates therapeutic approaches for diabetes.

I definitely understand that the decisions to cancel classes and close campus were made with consideration, but research isnt something you can just immediately pull out of, Brown said, who, like many students, acknowledged the necessity of the move while struggling to grapple with the effects of it.

Pooja Reddy 20 is a molecular and cell biology major that conducts research in Prof. Ankur Singhs lab, mechanical and aerospace engineering. For her honors thesis project, Reddy is studying how underlying health conditions, like metabolic syndrome, affect the effectiveness of vaccines.

In response to class cancellations, Reddy expressed concerns over finishing her experiments in time.

I planned on completing my experiments over the next 4 weeks to have them ready for my final thesis draft, but now I need to scramble to fit them all in two weeks, Reddy said. Having to do this while also saying goodbye to all my friends is super overwhelming and upsetting.

Claire Malkin 20, a computational biology major, works in Prof. Toshi Kawates lab, molecular medicine, studying the structure of a protein membrane receptor linked to chronic pain.

I was lucky to have just finished a lot of my data analysis so Im hoping that I can do work remotely, she said. [But] it is upsetting that we dont get to present our work, and its definitely harder to get feedback and continue work in the lab.

Even though Brown expressed frustration that many of us were planning to finish getting all of the data wed like to have during or after Spring Break, she appreciated steps being taken to accommodate undergraduates in the face of unforeseen circumstances.

I respect that measures are being taken to address the severity of this pandemic, and Im happy that we are still able to submit our theses for consideration at all, Brown said.

Whether these announced changes pertaining to biological sciences honors students will affect all undergraduate students doing research remains unclear.

For now, there is no specific guidance for students living off-campus, wrote Bill Loftus, director of administration for the Weill Institute for Cell and Molecular Biology, in an email sent to students and employees at the Weill Institute on Wednesday night. Presently, we do not know if undergrads can continue working in Institute labs after April 6. We are waiting for further clarification from the University.

Prof. Julia Thom-Levy, vice provost for academic innovation, did not respond for comment by the time of publication.

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In-Person Class Cancellations Halt Undergraduate Research on Campus - Cornell University The Cornell Daily Sun

As the new coronavirus makes its way around the world, doctors and researchers are searching for drugs to treat the ill and stop the spread of the disease, which has already killed more than 3,800 people since its introduction in Wuhan, China, in December.

The culprit virus is in the same family as the coronavirusesthat caused two other outbreaks, severe acute respiratory syndrome and MiddleEast respiratory syndrome. But the new coronavirus may be more infectious. Inearly March, the number of confirmed cases of the new disease, called COVID-19,had exceeded 100,000, far surpassing the more than 10,600 combined total casesof SARS and MERS.

Health officials are mainly relying on quarantines to try tocontain the virus spread. Such low-tech public health measures were effectiveat stopping SARS in 2004, Anthony Fauci, director of the U.S. NationalInstitute of Allergy and Infectious Diseases, said January 29 in Arlington,Va., at the annual American Society for Microbiologys Biothreats meeting.

But stopping the new virus may require a more aggressive approach. In China alone, about 300 clinical trials are in the works to treat sick patients with standard antiviral therapies, such as interferons, as well as stem cells, traditional Chinese medicines including acupuncture, and blood plasma from people who have already recovered from the virus.

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Researchers are not stopping there. They also are working to develop drugs to treat infections and vaccines to prevent them (SN: 3/14/20, p. 6). But creating therapies against new diseases often takes years, if not decades. With this new coronavirus, now known as SARS-CoV-2, nobody wants to wait that long. Thanks to their experience developing treatments against the MERS coronavirus, as well as other diseases, such as HIV, hepatitis C, influenza, Ebola and malaria, researchers are moving quickly to see what they can borrow to help patients sooner.

Finding new uses for old drugs is a good strategy,especially when racing to fight a fast-moving disease for which there is notreatment, says Karla Satchell, a microbiologist and immunologist atNorthwestern University Feinberg School of Medicine in Chicago.

Repurposing drugs is absolutely the best thing that could happen right now, Satchell says. Potentially, drugs that combat HIV or hepatitis C might be able to put the new coronavirus in check, too. Those drugs exist. Theyve been produced. Theyve been tested in patients, she says. Although these drugs arent approved to treat the new coronavirus disease, theyre a great place to start. One of the most promising candidates, however, hasnt yet been approved for any disease.

Scientists have been quick to reveal the new coronavirussecrets. When SARS emerged in 2002, researchers took about five months to get acomplete picture of the viruss genetic makeup, or genome. With the new virus,Chinese health officials first reported a cluster of mysterious pneumonia casesin Wuhan to the World Health Organization on December 31. By January 10, thenew coronaviruss full genome was made available to researchers worldwide inpublic databases.

A viruss genome is one of the most valuable toolsscientists have for understanding where the pathogen came from, how it worksand how to fight it. The first thing that coronaviruses have in common is thattheir genetic material is RNA, a chemical cousin to DNA.

Researchers immediately began comparing the newcoronaviruss genome with SARS and MERS viruses and other RNA viruses todetermine whether drugs developed to combat those disease-causing organismswould work against the new threat. As a result, some potential Achilles heelsof SARS-CoV-2 have already come to light.

One target is the viruss main protein-cutting enzyme,called M protease. RNA viruses often make one long string of proteins thatlater get cut into individual proteins to form various parts of the virus. Inthe new coronavirus, the M protease is one of 16 proteins that are linked likebeads on a string, says Stephen Burley, an oncologist and structural biologistat Rutgers University in Piscataway, N.J.

The virus can mature and infect new cells only if M proteasecan snip the string of proteins free, he says. Stop the protease from cuttingand the virus cant reproduce, or replicate.

Existing drugs might be able to stop the viruss M protease, two research groups proposed online January 29 at bioRxiv.org. One group suggested four drugs, including one used to treat hepatitis C and two aimed at HIV. A second group named 10candidates, including an anti-nausea medication, an antifungal drug and some cancer-fighting drugs.

HIV and hepatitis C are both RNA viruses that need aprotease to cut proteins free from long chains. Drugs that inhibit thoseproteases can reduce levels of the HIV and hepatitis C viruses to undetectable.Some of those drugs are now being tested against the new coronavirus inclinical trials in China.

The HIV drug Kaletra, also called Aluvia, is a combination of two protease inhibitors, lopinavir and ritonavir. Kaletras maker, the global pharmaceutical company AbbVie, announced on January 26 that it is donating the drug to be tested in COVID-19 patients in China. Kaletra will be tested alone or in combination with other drugs. For instance, researchers may combine Kaletra with Arbidol, a drug that prevents some viruses from fusing with and infecting human cells. Arbidol may be tested on its own as well.

But the HIV drugs may not work against the new virus because of two differences in the proteases. The coronavirus protease cuts proteins in different spots than the HIV protease does, say Guangdi Li of the Xiangya School of Public Health of Central South University in Changsha, China, and Erik De Clercq, a pioneer in HIV therapy at KU Leuven in Belgium. Secondly, the HIV drugs were designed to fit a pocket in HIVs protease that doesnt exist in the new coronaviruss protease, the researchers reported February 10 in Nature Reviews Drug Discovery.

Yet a few anecdotal accounts suggest the HIV drugs may help people with COVID-19 recover. Doctors at Rajavithi Hospital in Bangkok reported in a news briefing February 2 that they had treated a severely ill 70-year-old woman with high doses of a combination of lopinavir and ritonavir and the anti-influenza drug oseltamivir, which is sold as Tamiflu. Within 48 hours of treatment, the woman tested negative for the virus.

Her recovery may be due more to the HIV drugs than to oseltamivir. In 124 patients treated with oseltamivir at Zhongnan Hospital of Wuhan University, no effective outcomes were observed, doctors reported on February 7 in JAMA. Clinical trials in which these drugs are given to more people in carefully controlled conditions are needed to determine what to make of those isolated reports.

Researchers may be able to exploit a second weakness in thevirus: its copying process, specifically the enzymes known as RNA-dependent RNApolymerases that the virus uses to make copies of its RNA. Those enzymes areabsolutely essential, says Mark Denison, an evolutionary biologist atVanderbilt University School of Medicine in Nashville. If the enzyme doesntwork, you cant make new virus.

Denison and colleagues have been testing molecules that muckwith the copying machinery of RNA viruses. The molecules mimic the nucleotidesthat RNA polymerases string together to make viral genomes. Researchers havetested chemically altered versions of two RNA nucleotides adenosine andcytidine against a wide variety of RNA viruses in test tubes and in animals.The molecules get incorporated into the viral RNA and either stop it fromgrowing or they damage it by introducing mutations, Denison says.

One of the molecules that researchers are most excited aboutis an experimental drug called remdesivir. The drug is being tested in peoplewith COVID-19 because it can stop the MERS virus in the lab and in animalstudies. The drug has also been used in patients with Ebola, another RNA virus.

Remdesivir has been given to hundreds of people infected with Ebola, without causing serious side effects, but the drug hasnt been as effective as scientists had hoped, virologist Timothy Sheahan of the University of North Carolina at Chapel Hill said January 29 at the Biothreats meeting. In a clinical trial in Congo, for example, about 53 percent of Ebola patients treated with remdesivir died, researchers reported November 27 in the New England Journal of Medicine. Thats better than the 66 percent of infected people killed in the ongoing Ebola outbreak, but other drugs in the trial were more effective.

Several tests of remdesivir in lab animals infected with MERS have researchers still hopeful when it comes to the new coronavirus. In studies in both rhesus macaques and mice, remdesivir protected animals from lung damage whether the drug was given before or after infection. Molecular pathologist Emmie de Wit of NIAIDs Laboratory of Virology in Hamilton, Mont., and colleagues reported the monkey results February 13 in the Proceedings of the National Academy of Sciences.

Remdesivir appears to be one of the most promisingantiviral treatments tested in a nonhuman primate model to date, the teamwrote. The results also suggest remdesivir given before infection might helpprotect health care workers and family members of infected people from gettingsevere forms of the disease, Sheahan says.

Denison, Sheahan and colleagues tested remdesivir on infected human lung cells in the lab and in mice infected with MERS. Remdesivir was more potent at stopping the MERS virus than HIV drugs and interferon-beta, the researchers reported January 10 in Nature Communications.

But the question is still open about whether remdesivir canstop the new coronavirus.

In lab tests, it can. Both remdesivir and the antimalaria drug chloroquine inhibited the new viruss ability to infect and grow in monkey cells, virologist Manli Wang of the Wuhan Institute of Virology of the Chinese Academy of Sciences and colleagues reported February 4 in Cell Research. Remdesivir also stopped the virus from growing in human cells. Chloroquine can block infections by interfering with the ability of some viruses including coronaviruses to enter cells. Wang and colleagues found that the drug could also limit growth of the new coronavirus if given after entry. Chloroquine also may help the immune system fight the virus without the kind of overreaction that can lead to organ failure, the researchers propose.

In China, remdesivir is already being tested in patients. And NIAID announced February 25 that it had launched a clinical trial of remdesivir at the University of Nebraska Medical Center in Omaha. The first enrolled patient was an American evacuated from the Diamond Princess cruise ship in Japan that had been quarantined in February because of a COVID-19 outbreak.

Ultimately, nearly 400 sick people at 50 centers around theworld will participate in the NIAID trial, which will compare remdesivir with aplacebo. The trial may be stopped or altered to add other drugs depending onresults from the first 100 or so patients, says Andre Kalil, an infectiousdisease physician at the University of Nebraska Medical Center.

Researchers considered many potential therapies, but basedon results from the animal and lab studies, remdesivir seemed to be the onethat was more promising, Kalil says.

In the early patient studies, figuring out when to give remdesivirto patients might not be easy, Sheahan says. Often drugs are tested on thesickest patients. For example, those in the NIAID trial must have pneumonia toparticipate. By the time someone lands in the intensive care unit withCOVID-19, it may be too late for remdesivir to combat the virus, Sheahan says.It may turn out that the drug works best earlier in the disease, before viralreplication peaks.

We dont know because it hasnt really been evaluated inpeople how remdesivir will work, or if it will work at all, Sheahan cautions.

The drug seems to have helped a 35-year-old man in Snohomish County, Wash., researchers reported January 31 in the New England Journal of Medicine. The man had the first confirmed case of COVID-19 in the United States. He developed pneumonia, and doctors treated him with intravenous remdesivir. By the next day, he was feeling better and was taken off supplemental oxygen.

Thats just one case, and the company that makes remdesivirhas urged caution. Remdesivir is not yet licensed or approved anywhereglobally and has not been demonstrated to be safe or effective for any use,the drugs maker, biopharmaceutical company Gilead Sciences, headquartered inFoster City, Calif., said in a statement on January 31.

But global health officials are eager to see the drug testedin people. Theres only one drug right now that we think may have realefficacy, and thats remdesivir, WHOs assistant director-general BruceAylward said during a news briefing on February 24. But researchers in Chinaare having trouble recruiting patients into remdesivir studies, partly becausethe number of cases has been waning and partly because too many trials ofless-promising candidates are being offered. We have got to start prioritizingenrollment into those things that may save lives and save them faster, Aylwardsaid.

Another strategy for combating COVID-19 involves distracting the virus with decoys. Like the SARS virus, the new virus enters human cells by latching on to a protein called ACE2. The protein studs the surface of cells in the lungs and many other organs. A protein on the surface of the new virus binds to ACE2 10 to 20 times as tightly as the SARS protein does.

Researchers at Vienna-based Apeiron Biologics announced February 26 that they would use human ACE2 protein in a clinical trial against the new coronavirus. When released into the body, the extra ACE2 acts as a decoy, glomming on to the virus, preventing it from getting into cells.

ACE2 isnt just a viruss doorway to infection. Normally, it helps protect the lungs against damage, says Josef Penninger, an immunologist at the University of British Columbia in Vancouver and a cofounder of Apeiron. Penninger and colleagues reported the proteins protective qualities, based on studies with mice, in Nature in 2005.

During a viral infection, the protein is drawn away from thecell surface and cant offer protection. Penninger thinks that adding in extraACE2 may help shield the lungs from damage caused by the virus and by immunesystem overreactions. The protein is also made in many other organs. Penningerand colleagues are testing whether the new virus can enter other tissues, whichmight be how the virus leads to multiple organ failures in severely ill people.

The decoy protein drug, called APN01, has already beenthrough Phase I and Phase II clinical testing. We know its safe, Penningersays. Now researchers just need to determine whether it works.

No one knows whether any of these approaches can help stemthe spread of COVID-19.

Right now, we need lots of people working with lots ofideas, Satchell says. Similarities between the viruses that cause SARS andCOVID-19 may mean that some drugs could work against both. There is a hopethat several small molecules that were identified as inhibitors of the SARSprotease would represent reasonable starting points for trying to make a drugfor the 2019 coronavirus, Burley says.

The open questionis, can you produce a drug that is both safe and effective quickly enough tohave an impact? SARS was stopped by traditional infection-control measures in2004, before any virus-fighting drugs made it through the development pipeline.

But had a decision been made then to spend $1 billion tomake a safe and effective drug against SARS, Burley says, such a drug might beworking now against the new coronavirus, eliminating the need to spend hundredsof billions of dollars to contain this new infection.

An investment in SARS would not have paid off for peoplewith MERS, which is still a danger in the Middle East. The MERS virus is toodifferent from SARS at the RNA level for SARS drugs to work against it.

But a future coronavirus might emerge that is similar enough to SARS and SARS-CoV-2 to be worth the cost, Burley says. Even if the current outbreak dwindles and disappears, he says, governments and companies should keep investing in drugs that can stop coronaviruses.

Im quite certain that the economic impact of the epidemic is going to run into the hundreds of billions, he says. So you would only need a 1 percent chance of something that was treatable with the drug to show up in the future to have made a good investment.

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Repurposed drugs may help scientists fight the new coronavirus - Science News

Internationally renowned neurodegeneration academic, Professor Glenda Halliday, who is shaping the treatment of non-Alzheimers dementias and Parkinsons disease, has been recognised as one of Australias leading female medical researchers.

Professor Halliday, from the Faculty of Medicine and Health and the Brain and Mind Centre, was awarded the NHMRC Elizabeth Blackburn Investigator Grant Award for Leadership in Clinical Medicine and Science.

The award is named in honour of Professor Elizabeth Blackburn, an Australian molecular biologist who received the Nobel Prize in Physiology or Medicine in 2009.

Professor Hallidays groundbreaking research has shaped current international diagnostic criteria and recommendations for neurodegenerative patient identification and management.

After developing quantitative methods to evaluate the symptoms of patients with Parkinson's disease, she revealed more extensive neurodegeneration in Parkinson's and related syndromes than previously thought.

Her 70 strong research team in the Brain and Mind Centres Dementia and Movement Disorders Lab is now focused on finding biomarkers that identify under-recognised non-Alzheimer diseases to target with disease modifying strategies.

Deputy Vice-Chancellor (Research) Professor Duncan Ivison congratulated Professor Halliday on this prestigious award, adding that her work is at the forefront of understanding the origins of neurodegeneration and developing new treatments.

Glenda has rightly been recognised as one of Australias, and the worlds, leading experts on neurodegeneration. Her research is critical to improving the lives of those with Parkinsons, dementia and other neurodegenerative diseases and we are proud to support her and her team to conduct this important research.

Professor Halliday has produced more than 430 publications, has a h-index of 83, and was named among the world's most influential academics on the Clarivate Analytics 2019 Highly Cited Researchers List.

She is on the editorial boards of five international journals, and on the scientific advisory boards for a number of international organisations and research institutes. She is a Fellow of the Australian Academy of Health and Medical Sciences.

The University of Sydney is ranked 18th in the world for medicine, according to the latest QS Subject rankings.

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Renowned neurodegeneration expert receives top accolade - News - The University of Sydney

A central promise of regenerative medicine is the ability to repair aged or diseased organs using stem cells (SCs). This approach will likely become an effective strategy for organ rejuvenation, holding the potential to increase human health by delaying age-related diseases (1). The successful translation of this scientific knowledge into clinical practice will require a better understanding of the basic mechanisms of aging, along with an integrated view of the process of tissue repair (1).

The advent of SC therapies, now progressing into clinical trials, has made clear the many challenges limiting the application of SCs to treat disease. Our duty, as scientists, is to anticipate such limitations and propose solutions to effectively deliver on the promise of regenerative medicine.

Degenerating tissues have difficulty engaging a regulated repair response that can support efficient cell engraftment and restoration of tissue function (2). This problem, which I encountered when trying to apply SC-based interventions to treat retinal disease, will likely be an important roadblock to the clinical application of regenerative medicine approaches in elderly patients, those most likely to benefit from such interventions. I therefore hypothesized that the inflammatory environment present in aged and diseased tissues would be a major roadblock for efficient repair and that finding immune modulators with the ability to resolve chronic inflammation and promote a prorepair environment would be an efficient approach to improve the success of SC-based therapies (2, 3).

Immune cells, as sources and targets of inflammatory signals, emerged naturally as an ideal target for intervention. I chose to focus on macrophages, which are immune cells of myeloid origin that exist in virtually every tissue of the human body and which are able to reversibly polarize into specific phenotypes, a property that is essential to coordinate tissue repair (3, 4).

If there is an integral immune modulatory component to the process of tissue repair that has evolved to support the healing of damaged tissues, then it should be possible to find strategies to harness this endogenous mechanism and improve regenerative therapies. Anchored in the idea that tissue damage responses are evolutionarily conserved (5), I started my research on this topic using the fruit fly Drosophila as a discovery system.

The fruit fly is equipped with an innate immune system, which is an important player in the process of tissue repair. Using a well-established model of tissue damage, I sought to determine which genes in immune cells are responsible for their prorepair activity. MANF (mesencephalic astrocyte-derived neurotrophic factor), a poorly characterized protein initially identified as a neurotrophic factor, emerged as a potential candidate (6). A series of genetic manipulations involving the silencing and overexpression of MANF and known interacting partners led me to the surprising discovery that, instead of behaving as a neurotrophic factor, MANF was operating as an autocrine immune modulator and that this activity was essential for its prorepair effects (2). Using a model of acute retinal damage in mice and in vitro models, I went on to show that this was an evolutionarily conserved mechanism and that MANF function could be harnessed to limit retinal damage elicited by multiple triggers, highlighting its potential for clinical application in the treatment of retinal disease (2).

Having discovered a new immune modulator that sustained endogenous tissue repair, I set out to test my initial hypothesis that this factor might be used to improve the success of SC-based therapies applied to a degenerating retina. Indeed, the low integration efficiency of replacement photoreceptors transplanted into congenitally blind mice could be fully restored to match the efficiency obtained in nondiseased mice by supplying MANF as a co-adjuvant with the transplants (2). This intervention improved restoration of visual function in treated mice, supporting the utility of this approach in the clinic (7).

Next, my colleagues and I decided to address the question of whether the immune modulatory mechanism described above was relevant for aging biology and whether we could harness its potential to extend health span. We found that MANF levels are systemically decreased in aged flies, mice, and humans. Genetic manipulation of MANF expression in flies and mice revealed that MANF is necessary to limit age-related inflammation and maintain tissue homeostasis in young organisms. Using heterochronic parabiosis, an experimental paradigm that involves the surgical joining of the circulatory systems of young and old mice, we established that MANF is one of the circulatory factors responsible for the rejuvenating effects of young blood. Finally, we showed that pharmacologic interventions involving systemic delivery of MANF protein to old mice are effective therapeutic approaches to reverse several hallmarks of tissue aging (8).

A confocal fluorescence microscope image of a giant macrophage shows MANF (mesencephalic astrocyte-derived neurotrophic factor) expression in red.

The biological process of aging is multifactorial, necessitating combined and integrated interventions that can simultaneously target several of the underlying problems (9). The potential of immune modulatory interventions as rejuvenating strategies is emerging and requires a deeper understanding of its underlying molecular and cellular mechanisms.

One expected outcome of reestablishing a regulated inflammatory response is the optimization of tissue repair capacity that naturally decreases during aging (3). Combining these interventions with SCbased therapeutics holds potential to deliver on the promise of regenerative medicine as a path to rejuvenation (1).

PHOTO: COURTESY OF J. NEVES

GRAND PRIZE WINNER

Joana Neves

Joana Neves received undergraduate degrees from NOVA University in Lisbon and a Ph.D. from the Pompeu Fabra University in Barcelona. After completing her postdoctoral fellowship at the Buck Institute for Research on Aging in California, Neves started her lab in the Instituto de Medicina Molecular (iMM) at the Faculty of Medicine, University of Lisbon in 2019. Her research uses fly and mouse models to understand the immune modulatory component of tissue repair and develop stem cellbased therapies for age-related disease.

PHOTO: COURTESY OF A. SHARMA

FINALIST

Arun Sharma

Arun Sharma received his undergraduate degree from Duke University and a Ph.D. from Stanford University. Having completed a postdoctoral fellowship at the Harvard Medical School, Sharma is now a senior research fellow jointly appointed at the Smidt Heart Institute and Board of Governors Regenerative Medicine Institute at the Cedars-Sinai Medical Center in Los Angeles. His research seeks to develop in vitro platforms for cardiovascular disease modeling and drug cardiotoxicity assessment. http://www.sciencemag.org/content/367/6483/1206.1

FINALIST

Adam C. Wilkinson

Adam C. Wilkinson received his undergraduate degree from the University of Oxford and a Ph.D. from the University of Cambridge. He is currently completing his postdoctoral fellowship at the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University, where he is studying normal and malignant hematopoietic stem cell biology with the aim of identifying new biological mechanisms underlying hematological diseases and improving the diagnosis and treatment of these disorders. http://www.sciencemag.org/content/367/6483/1206.2

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Aging eyes and the immune system - Science Magazine

Pandemic /pandemik/ (of a disease) prevalent over a whole country or the world.

As humans have spread across the world, so have infectious diseases. Even in this modern era, outbreaks are nearly constant, though not every outbreak reaches pandemic level as the Novel Coronavirus (COVID-19) has.

Todays visualization outlines some of historys most deadly pandemics, from the Antonine Plague to the current COVID-19 event.

Disease and illnesses have plagued humanity since the earliest days, our mortal flaw. However, it was not until the marked shift to agrarian communities that the scale and spread of these diseases increased dramatically.

Widespread trade created new opportunities for human and animal interactions that sped up such epidemics. Malaria, tuberculosis, leprosy, influenza, smallpox, and others first appeared during these early years.

The more civilized humans became with larger cities, more exotic trade routes, and increased contact with different populations of people, animals, and ecosystems the more likely pandemics would occur.

Here are some of the major pandemics that have occurred over time:

Note: Many of the death toll numbers listed above are best estimates based on available research. Some, such as the Plague of Justinian, are subject to debate based on new evidence.

Despite the persistence of disease and pandemics throughout history, theres one consistent trend over time a gradual reduction in the death rate. Healthcare improvements and understanding the factors that incubate pandemics have been powerful tools in mitigating their impact.

In many ancient societies, people believed that spirits and gods inflicted disease and destruction upon those that deserved their wrath. This unscientific perception often led to disastrous responses that resulted in the deaths of thousands, if not millions.

In the case of Justinians plague, the Byzantine historian Procopius of Caesarea traced the origins of the plague (the Yersinia pestis bacteria) to China and northeast India, via land and sea trade routes to Egypt where it entered the Byzantine Empire through Mediterranean ports.

Despite his apparent knowledge of the role geography and trade played in this spread, Procopius laid blame for the outbreak on the Emperor Justinian, declaring him to be either a devil, or invoking Gods punishment for his evil ways. Some historians found that this event could have dashed Emperor Justinians efforts to reunite the Western and Eastern remnants of the Roman Empire, and marked the beginning of the Dark Ages.

Luckily, humanitys understanding of the causes of disease has improved, and this is resulting in a drastic improvement in the response to modern pandemics, albeit slow and incomplete.

The practice of quarantine began during the 14th century, in an effort to protect coastal cities from plague epidemics. Cautious port authorities required ships arriving in Venice from infected ports to sit at anchor for 40 days before landing the origin of the word quarantine from the Italian quaranta giorni, or 40 days.

One of the first instances of relying on geography and statistical analysis was in mid-19th century London, during a cholera outbreak. In 1854, Dr. John Snow came to the conclusion that cholera was spreading via tainted water and decided to display neighborhood mortality data directly on a map. This method revealed a cluster of cases around a specific pump from which people were drawing their water from.

While the interactions created through trade and urban life play a pivotal role, it is also the virulent nature of particular diseases that indicate the trajectory of a pandemic.

Scientists use a basic measure to track the infectiousness of a disease called the reproduction number also known as R0 or R naught. This number tells us how many susceptible people, on average, each sick person will in turn infect.

Measles tops the list, being the most contagious with a R0 range of 12-18. This means a single person can infect, on average, 12 to 18 people in an unvaccinated population.

While measles may be the most virulent, vaccination efforts and herd immunity can curb its spread. The more people are immune to a disease, the less likely it is to proliferate, making vaccinations critical to prevent the resurgence of known and treatable diseases.

Its hard to calculate and forecast the true impact of COVID-19, as the outbreak is still ongoing and researchers are still learning about this new form of coronavirus.

We arrive at where we began, with rising global connections and interactions as a driving force behind pandemics. From small hunting and gathering tribes to the metropolis, humanitys reliance on one another has also sparked opportunities for disease to spread.

Urbanization in the developing world is bringing more and more rural residents into denser neighborhoods, while population increases are putting greater pressure on the environment. At the same time, passenger air traffic nearly doubled in the past decade. These macro trends are having a profound impact on the spread of infectious disease.

As organizations and governments around the world ask for citizens to practice social distancing to help reduce the rate of infection, the digital world is allowing people to maintain connections and commerce like never before.

Editors Note: The COVID-19 pandemic is in its early stages and it is obviously impossible to predict its future impact. This post and infographic are meant to provide historical context, and we will continue to update it as time goes on to maintain its accuracy.

Update (March 15, 2020): Weve adjusted the death toll for COVID-19, and will continue to update on a regular basis.

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Infographic: The History of Pandemics, by Death Toll - Visual Capitalist

Everyone is looking for silver-linings in the COVID-19 pandemic, which is only natural. In the tech sector, for example, many people have decided that one of the up-sides of the crisis is that it has demonstrated the fantastic power of artificial intelligence.

The argument is that AI helped doctors anticipate, diagnose, and formulate treatments for COVID-19.

The truth is somewhat less fantastic.

In MITs Technology Review, Will Douglas debunked these claims, concluding that AI could help with the next pandemicbut not with this one. Where AI has made an impact, its been in ways that we might not like. The Wall Street Journals Tech News podcast points out that the most consequential implementation of AI during this crisis may have been Chinas use of facial recognition to identify and report citizens who were using public transportation without wearing masks.

In other words, so far AI has been most useful as a means to extending an authoritarian regimes surveillance capabilities, and in this one instance that may have contributed some unmeasurable public health benefit. Yay?

And advances in the biotech sector have not been terribly impressive, either.

We are more than 60 years into the molecular age (Watson and Crick first published their double helix structure of DNA in 1953) and the two most valuable remediation techniques at our disposal are the admonitions to (1) wash your hands and (2) isolate the afflicted. According to the CDC, this latter technique was developed in the Middle Ages.

This isnt to say that weve learned nothing in the ensuing 700 years: the supportive care afforded to those who are critically ill is an extraordinary achievement, the result of iterativeand often unheraldedimprovements in processes over time. And it seems that real and rapid progress is being made toward the development of potential therapies (to treat the disease), and vaccines (to protect from it)but the proof here will be in the eventual clinical trials.

To their credit, physicians and other health care providers tend to be painfully aware of the limitations of their armamentarium, and feel a powerful sense of humility in response to this pandemic.

Yet the worst attitude elicited by the current crisis isnt hubris, but disdain. There is a sense emanating from certain sectors that there would be karmic justice if MAGA zealots who believe more strongly in the Deep State than in science were to become preferentially infected with coronavirus because they dismissed precautions around social distancing and regarded these public health admonitions as an anti-Trump conspiracy.

You may have heard of the Darwin Award, the satirical prize given to people who are killed by their own foolishness. Example: A lawyer who dies after running through a skyscraper window, trying to demonstrate its safety. Or a rhino poacher stomped to death by an elephant (then digested by a lion).

There is, here and there in the tech and science communities, the whispered belief that Trump supporters who disdain public health advice like social distancing are lining up to win their own Darwin Awards and that if they start dropping like flies, they will have gotten what they deserved.

This notion is deplorable and runs directly counter to the spirit of medicine. And it must be stamped out. Immediately.

One of the best things about being a doctor is the bedrock commitment to helping each person in need. When you approach a patient as a physician, you dont take on the complex moral calculus of how complicit someone may or may not be in their condition, and then titrate care and concern accordingly. You attend to each person equally, and without qualification.

Beyond that, to be a physician is to recognize that diseases afflict all of us; while those with the least are often the most susceptible to illness, all of us can, at a moments notice, move from the realm of the well to the realm of the sick. As Susan Sontag eloquently wrote,

Illness is the night-side of life, a more onerous citizenship. Everyone who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick. Although we all prefer to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place.

As long as disease has existed, theres been a tendency to attribute illness to a failing of the sufferer; yet while someones behavior and choices often plays a role in illnesssmoking predisposes to lung cancer, and obesity contributes to the prevalence of type 2 diabetesdoctors know that although prevention is important, illness can strike anyone. Which is why physicians aspire to offer you understanding, rather than judgment.

When I started my medical training, one of the things which struck me is just how much so many people are dealing with, all the time. We get a sense of this from the occasional celebrity revelations: rapper Lil Wayne coping with epilepsy; Giants great Tiki Barber managing his sickle cell disease; Supreme Court Justice Sonia Sotomayor living with type 1 diabetes since she was a child; the revelation that President John F. Kennedy suffered from an adrenal gland deficiency called Addisons Disease; and former Colorado Governor John Hickenlooper, former Illinois Senator Carol Moseley Braun, and Colorados senior Senator Michael Bennet, who each have overcome dyslexia.

The arrival of a global pandemic upon our shores, despite the insistent skepticism of the president and his supporters, should not be looked at as a victory of science over the heathens.

Instead, this pandemic should remind us just how far science and technology still have to go, while reawakening our sense of responsibility to care for all the afflicted, to the best of our ability, and with all our hearts.

The most appropriate response to misplaced arrogance and self-regard isnt the transposition of these qualities from politicians to scientists.

Its to replace these reflexes with the humility that science demands, and the empathy our patientsall of themdeserve.

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We Can Be Better Than COVID-19 - The Bulwark

By Michael Tutton, The Canadian Press on March 15, 2020.

HALIFAX For a Halifax father and daughter dedicated to taking on global infectious diseases, the novel coronavirus has led to their latest, exhausting push to create tests and vaccines to save lives.

Alyson Kelvin, 39, and David Kelvin, 65, are once again in the trenches of a race to find long-term solutions, hoping for success while public interest and funding remain in place.

Alyson, a virologist working at Dalhousie University, has been seconded to the Vaccine and Infectious Disease Organization International Vaccine Centre in Saskatoon since mid-February to test vaccines in lab animals.

Meanwhile, back in Halifax, her father a professor in Dalhousies department of microbiology and immunology is immersed in creating a portable test kit to identify the severity of the illness for people who test positive for the virus.

Both are engaged in rapid response science, which has meant fast-tracked federal funding is paired with swift collaboration with scientists around the globe working on the pandemic.

I work from waking up until going to sleep, the younger Kelvin said during an interview from Saskatoon. My whole life has shifted. My husband and children are back in Halifax.

The pursuit of infectious disease solutions is a family passion, she adds.

Thats how I was raised, she says, referring to her observation of her fathers work on HIV-AIDS as a young woman.

Her career has already included work on the first SARS outbreak, the Zika virus and various influenza outbreaks. Her father has worked on many of the same outbreaks.

David Kelvin has several projects on the go, including a push to identify biomarkers in this instance molecules that activate white blood cells that will indicate if a person who tests positive for the virus is at risk of developing a severe case of COVID-19.

The goal is to create a kit that would allow health care providers to determine in as little as 20 minutes who needs to be hospitalized, which could potentially keep vitally needed beds and respirators open for patients most in need.

Rather than going through a lengthy process of days, we can do it rapidly and provide assistance to doctors who are looking at a surge of patients and can decide who should receive hospitalization at the earlier stages of the disease, he explained in an interview.

In Saskatoon, his daughter, accompanied by a doctoral student and technician from Dalhousie, is working with coronavirus investigator Darryl Falzarano at the International Vaccine Centre to carry out animal tests for potential vaccines.

Her knowledge of ferrets is key as the animal was identified as a helpful model for human immune reactions in the SARS outbreak in 2002-03, and is believed to also be a useful lab animal for testing vaccines for the novel coronavirus.

Her team is working with three vaccines developed by Halifax molecular virologist Chris Richardson, also a Dalhousie University scientist, and a vaccine developed by a scientist at the centre.

While their work has to move as swiftly as possible, she says that doesnt mean compromising a meticulous methodology to avoid any safety risks. Without animal-testing stages in vaccine research, its possible errors can occur, she said.

Its especially important because the original SARS vaccines werent effective and sometimes led to more severe disease in the end. So, this is an important stage of the evaluation, she said.

Having vaccines a year from now for the novel coronavirus may still be vital, the researcher said.

We may see waves of it in the same way we do with influenza . Having a vaccine and being ready for this particular virus could help us if that becomes a reality, she said.

Richardson, who has worked in the field for four decades, said regular vaccine research can take several years.

Typically it could be two years and clinical trials can go even further, he said in an interview.

He says one of the frustrations is that funding can dry up after an outbreak prompts an initial surge in interest. The veteran virologist said he hopes it will be different this time.

The father and daughter both say they are relying on Ottawa to keep funding flowing in the months to come, even if the pandemic calms.

This call for the initial research was $1 million, David Kelvin said. Its a fantastic initial start. We realize and know that to continue this through the full duration of the infection cycle, were going to have to have a lot more investment.

Hes hopeful the biomarkers for the potential test kits will emerge from his collaborators in China and Italy in four to 10 weeks, but further work will then require commercial collaborators interested in producing the kits.

The family connections in the research are likely to continue. Alyson Kelvin said that as her fathers teams kits evolve, her team will be able to test their effectiveness.

We can experimentally induce viral infection and disease, and we can evaluate the kits using samples from our experiments before theyre used in people, she said.

Amid the current pressure for results, David Kelvin says it may be time for government to reflect on whether the funding for vaccine research should have been in place sooner and on a steadier basis.

Too often, he says, interest has faded when the worst of an international infection passes.

We need to impress on everyone this is our third pandemic in 20 years, he said. We dont want to respond in an emergency fashion every time. We want to be really well prepared.

This report by The Canadian Press was first published March 15, 2020.

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Rapid response COVID-19 science conducted by father and daughter virologists - Medicine Hat News

Precision Molecular, Inc. (PMI), a clinical-stage company with the mission to develop imaging biomarkers and theranostics, today announced that the Alzheimers Drug Discovery Foundation (ADDF) made an investment in the company to support advancement of more effective ways to image neuroinflammation, with a view to discovery of early imaging biomarkers for Alzheimers disease. Terms of the investment were not disclosed.

"We welcome the investment by ADDF to help advance this important work," said Martin Pomper, M.D, Ph.D., Founder and CEO of PMI. "We and others have used radioligands targeting the translocator protein for positron emission tomography (PET) in an effort to measure activated microglia a hallmark of neuroinflammation in patients with a variety of putative neuroinflammatory conditions. Unfortunately, that approach is fraught with poor cell selectivity and high variability. The radiotracer being developed by PMI was chosen to offer greater cell specificity with the potential for earlier and more definitive detection of neuroinflammation." Dr. Pomper is the Henry N. Wagner, Jr. professor in the Russell H. Morgan Department of Radiology and Radiological Science at Johns Hopkins School of Medicine.

PMIs radiotracer, PMI04, binds the macrophage colony stimulating factor 1 receptor (CSF1R) which, in the brain, is found almost exclusively on microglia and infiltrating macrophages, cell types directly involved in inflammation. In an article published in PNAS, uptake of the PMI radiotracer in inflamed brain tissue was shown to be approximately twice that of healthy brain tissue in animal models. Likewise, binding in postmortem Alzheimers brain tissue was about twice that of healthy tissue. Radiotracer uptake could be completely blocked by pretreating with other CSF1R ligands, demonstrating high specificity for the target.

"Imaging agents such as the one being developed by PMI are essential to advancing our ability to diagnose Alzheimers and to develop new therapeutics," said Howard Fillit, M.D., founding executive director and chief science officer of the ADDF. "The ADDF is pleased to support this important work and we look forward to seeing the results of ongoing clinical studies."

Investment in this program was provided by the ADDF through one of several active funding programs. The ADDF is a non-profit organization solely focused on funding the development of drugs for Alzheimer's, employing a venture philanthropy model to support research in academia and the biotech industry. The ADDF has awarded more than $150 million to fund over 626 Alzheimer's drug discovery programs and clinical trials in 19 countries. To learn more about ADDF, visit the website at http://www.alzdiscovery.org.

In addition to potential applications for detecting and following Alzheimers disease, this radiotracer can also be used to identify and track neuroinflammation in patients with Parkinsons disease. In December 2019, Johns Hopkins University received a grant from the Michael J. Fox Foundation (MJFF) to study PMI04 for imaging microglia-selective inflammation in patients with Parkinsons disease.

https://www.michaeljfox.org/grant/development-colony-stimulating-factor-1-receptor-csf1r-radioligand-imaging-microglia

About PMIPrecision Molecular, Inc. (PMI) is a clinical-stage company with the mission to develop imaging biomarkers and theranostics (targeted therapy combined with diagnostics) for management of patients with CNS disorders and cancer. PMI is advancing a number of imaging biomarker products in the clinic with great potential to improve early diagnosis of neurodegenerative diseases and cancer. Utilizing these imaging biomarkers to follow disease progression may provide clinical researchers with powerful tools for early assessment of drug efficacy in clinical trials. PMI is a subsidiary of D&D Pharmatech, a clinical-stage global biotech company that funds the development of revolutionary medicines through disease-specific subsidiary companies founded and guided by top-tier medical research faculty and biotechnology veterans. This corporate structure creates a unique opportunity to accelerate translation of cutting-edge research into lifesaving therapeutic products for patients. For more information about D&D Pharmatech and Precision Molecular, Inc., please visit http://www.ddpharmatech.com/

View source version on businesswire.com: https://www.businesswire.com/news/home/20200218005073/en/

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Precision Molecular Announces Investment by Alzheimers Drug Discovery Foundation to Support Advancement of More Effective Agents for Imaging...

Studies by researchers at University of South Florida Health (USF Health) Morsani College of Medicine have found that a protein known as -arrestin2 increases the accumulation of the neurotoxic tau tangles that cause several forms of dementia, by interfering with the process that cells use to remove excess tau from the brain. The studies demonstrated that an oligomerized form of -arrestin2, but not monomeric -arrestin2, disrupted the process of autophagy, which would normally act to help rid cells of malformed proteins like disease-causing tau.

Encouragingly, in vivo studies showed that blocking -arrestin2 oligomerization suppressed disease-causing tau in a mouse model that develops a form of human frontotemporal lobar degeneration (FTLD) with dementia, a form of neurodegeneration that is characterized by tau accumulation and the formation of neurofibrillary tangles. Our research could lead to a new strategy to block tau pathology in FTLD, Alzheimers disease, and other related dementias, which ultimately destroys cognitive abilities such as reasoning, behavior, language, and memory, said Jung-A (Alexa) Woo, PhD, an assistant professor of molecular pharmacology and physiology and an investigator at the USF Health Byrd Alzheimers Center. Woo is lead author of the teams published paper in theProceedings of the National Academy of Sciences(PNAS), which is titled, -arrestin2 oligomers impair the clearance of pathological tau and increase tau aggregates.

FTLD, which is also called frontotemporal dementia, is second only to Alzheimers disease (AD) as the leading cause of dementia. This aggressive form of dementia is typically earlier onset, in people aged 4565, and is characterized by atrophy of the front or side regions of the brain, or both. The two primary hallmarks of Alzheimers disease are clumps of amyloid-beta (A) protein fragments known as amyloid plaques, and the tangles of tau protein. Abnormal accumulations of both proteins are needed to drive the death neurons in Alzheimers, although recent research suggests that tau accumulation appears to be required for the toxic effects of A in AD, and correlates better with cognitive dysfunction than A. Indeed, tauopathy correlates significantly better than A with cognitive deficits in AD, the team noted, and drugs targeting A have been disappointing as a treatment.

Like Alzheimers disease, FTLD displays an accumulation of tau, which results in the formation of tau-laden neurofibrillary tangles that destroy synaptic communication between neurons, eventually killing the brain cells. There is no specific treatment or cure for FTLD. However, in contrast with AD, A aggregation is absent in the FTLD brain, in which the key feature of neurodegeneration appears to be the excessive tau accumulation, known as tauopathy. In contrast to AD, where amyloid is an integral part of the tangle, there is no accumulation of A in FTLD neurons , the authors noted.

Previous studies have pointed to an association between G protein-coupled receptors (GPCRs) and AD pathogenesis, and have linked the activation of several, diverse GPCRs with A and/or tau pathogenesis in animal models. While it isnt clear how these very different GPCRs can impact on A and tau pathogenesis, and neurodegeneration in AD, one potential commonality among the receptors is their interaction with arrestins, the researchers noted. Interestingly, previous studies have shown that one of the family of -arrestin proteins known as -arrestin2, is increased in AD brains, and genetic studies have shown that endogenous -arrestin2 promotes A production and deposition, linking -arrestin2 to A pathogenesis. Despite this evidence, the authors acknowledged, prior to the current work, however, it was not known whether, or how, -arrestin2 pathogenically impinges on tauopathy and neurodegeneration in AD, or in FTLD where there is no accumulation of A. As Woo commented, Studying FTLD gave us that window to study a key feature of both types of dementias, without the confusion of any A component.

-arrestin2 in its monomeric form is mostly known for its ability to regulate receptors, but -arrestin2 can also form multiple interconnecting units, called oligomers, and the function of -arrestin2 oligomers is not well understood. While the monomeric form was the basis for the laboratorys initial studies examining tau and its relationship with neurotransmission and receptors, Woo said, we soon became transfixed on these oligomers of -arrestin2.

The teams studies confirmed the presence of elevated -arrestin2 levels, both in cells from the brains of TFLD-tau patients, and in a mouse model. This model expresses disease-associated tau in neurons, and displays FTLD-like pathophysiology and behavior and, like FTLD in humans, doesnt accumulate A.

The researchers also found that -arrestin2 acts to increase tau stability via scaffolding potein:protein interactions. Their results indicated that when -arrestin2 is overexpressed, tau levels also increase, suggesting a maladaptive feedback cycle that exacerbates disease-causing tau. As the authors commented, the data suggested that increased tau increases -arrestin2, which in turn acts to further potentiate tau-mediated events by stabilizing the protein, thus indicative of a vicious positive pathogenic feedback cycle.

To determine the effects of reducing -arrestin2 levels, the team crossed a mouse model of early tauopathy with genetically modified mice in which the -arrestin2 gene was inactivated. They demonstrated that genetic knockdown of -arrestin2 also reduced tauopathy, synaptic dysfunction, and the loss of nerve cells and their connections in the brain. Importantly, experiments confirmed that it was oligomerized -arrestin2, and not the proteins monomeric form, which was associated with increased tau. By blocking -arrestin2 molecules from binding together to create oligomerized forms of the protein, the investigators demonstrated that pathogenic tau significantly decreased when only monomeric -arrestin2, which does bind to receptors, was present.

Further experiments indicated that oligomerized -arrestin2 increases tau by impeding the ability of cargo protein p62 to help selectively degrade excess tau in the brain. In effect, this reduces the efficiency of the autophagy process that would otherwise clear toxic tau. The resulting accumulation of tau clogs up the neurons. Blocking -arrestin2 oligomerization also suppressed disease-causing tau in the mouse model that develops human tauopathy with signs of dementia.

Specifically, our results indicate that -arrestin2 oligomers increase tau levels by blocking the self-interaction of p62, an initial step essential in p62-mediated autophagy flux, the team commented. Genetic reduction or ablation of -arrestin2 significantly decreased sarkosyl-insoluble tau and mitigated tauopathy in vivo. Furthermore, -arrestin2 mutants incapable of forming oligomersactually reduced insoluble tau.

It has always been puzzling why the brain cannot clear accumulating tau, said Stephen B. Liggett, MD, senior author and professor of medicine and medical engineering at the USF Health Morsani College of Medicine. It appears that an incidental interaction between -arrestin2 and the tau clearance mechanism occurs, leading to these dementias. -arrestin2 itself is not harmful, but this unanticipated interplay appears to be the basis for this mystery We also noted that decreasing -arrestin2 by gene therapy had no apparent side effects, but such a reduction was enough to open the tau clearance mechanism to full throttle, erasing the tau tangles like an eraser. This is something the field has been looking foran intervention that does no harm and reverses the disease.

The results point to a potential therapeutic strategy for tauopathies such as FTLD, based on partial inhibition of -arrestin2 oligomerization. For gene therapy of human FTLD-tau, mutants with a somewhat decreased capacity for such inhibition might be desirable, so that some levels of the oligomer are present to carry out other functions Similarly, small molecule inhibitors of -arrestin2 oligomerization, given for treatment or prevention of FTLD-tau, could be designed to spare complete loss of the oligomer in the cell, they suggested. Based on our findings, the effects of inhibiting -arrestin2 oligomerization would be expected to not only inhibit the development of new tau tangles, but also to clear existing tau accumulations due to this mechanism of enhancing tau clearance.

This treatment strategy could be both preventative for at-risk individuals and those with only mild cognitive impairment, and therapeutic in patients with evident FTLD-tau, by decreasing existing tau tangles. Beyond tauopathy, it is conceivable that this strategy could also prove to be beneficial in other neurodegenerative diseases bearing proteinopathies that are cleared via p62, the scientists concluded.

This study identifies beta-arrestin2 as a key culprit in the progressive accumulation of tau in brains of dementia patients, added co-author David Kang, PhD, professor of molecular medicine and director of basic research for the Byrd Alzheimers Center. It also clearly illustrates an innovative proof-of-concept strategy to therapeutically reduce pathological tau by specifically targeting beta-arrestin oligomerization.

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Protein that Prevents Tau Clearance Linked to AD and Other Tau Tangle Proteinopathies - Clinical OMICs News

A new business intelligence report released by Data Bridge Market Research with titleGlobal Bioinformatics Marketare taken from trustworthy sources such as websites, annual reports of the companies, journals, and others and were checked and validated by the market experts. Market research report is always helpful to business or organization in every subject of trade for taking better decisions, solving the toughest business questions and minimizing the risk of failure. Some of the key players profiled in the study areIllumina, Inc., NAnexus, Inc., Qiagen, Thermo Fisher Scientific, Inc., Agilent Technologies, Dassault Systmes, Geneva Bioinformatics (Genebio) SA, Integromics S.L., Perkinelmer, Inc., Applied Biological Materials (ABM).

Bioinformatics Market has accounted for USD 2.8 billion in 2016 and is expected to reach USD 7.69 billion by 2024, growing at a CAGR of 13.3% in the forecast period 2019 to 2024

Get Sample Report + All Related Graphs & Charts:https://www.databridgemarketresearch.com/request-a-sample/?dbmr=north-america-bioinformatics-market

Unlock new opportunities in Bioinformatics Market; the latest release from Data Bridge Market Research highlights the key market trends significant to the growth prospects, Let us know if any specific players or list of players needs to consider to gain better insights.

Competition Analysis:

Some of key competitors or manufacturers included in the study areIllumina, Inc., NAnexus, Inc., Qiagen, Thermo Fisher Scientific, Inc., Agilent Technologies, Dassault Systmes, Geneva Bioinformatics (Genebio) SA, Integromics S.L., Perkinelmer, Inc., Applied Biological Materials (ABM)

Research Methodology

This research study involves the extensive usage of secondary sources, directories, and databases (such as Hoovers, Bloomberg, Businessweek, Factiva, and OneSource) to identify and collect information useful for this technical, market-oriented, and commercial study of the global Bioinformatics market. In-depth interviews were conducted with various primary respondents, which include key industry participants, subject-matter experts (SMEs), C-level executives of key market players, and industry consultants, to obtain and verify critical qualitative and quantitative information, and assess future market prospects. The following figure shows the market research methodology applied in making this report on the global Bioinformatics market.

The titled segments and sub-section of the market are illuminated below:

Market By Industry (Molecular Medicine, Drug Development, Clinical Diagnostics, Agriculture, Forensic, Animal, Academics & Research, Environmental, Gene Therapy), By Product Type (Sequencing Platforms, Knowledge Management Tools, Bioinformatics Software),

By Application (Preventive Medicine, Molecular Medicine, Genomics, Drug Development, Transcriptomics, Others), By Services (Data Analysis, Sequencing, Database integration, Others)

Browse Full Report with Details TOC @https://www.databridgemarketresearch.com/toc/?dbmr=north-america-bioinformatics-market

Bioinformatics market report is an extraordinary report that makes it possible to the industry to take strategic decisions and achieve growth objectives. This report also provides the company profile, product specifications, production value, contact information of manufacturer and market shares for company. The Bioinformatics market report helps industry to make known the best market opportunities and look after proficient information to efficiently climb the ladder of success. The analysis of this report has been used to examine various segments that are relied upon to witness the quickest development based on the estimated forecast frame.

Chapters to deeply display the Global Bioinformatics market.

Introduction about Bioinformatics

Bioinformatics Market Size (Sales) Market Share by Type (Product Category) in 2017

Bioinformatics Market by Application/End Users

Bioinformatics Sales (Volume) and Market Share Comparison by Applications

(2013-2023) table defined for each application/end-users

Bioinformatics Sales and Growth Rate (2013-2023)

Bioinformatics Competition by Players/Suppliers, Region, Type and Application

Bioinformatics (Volume, Value and Sales Price) table defined for each geographic region defined.

Bioinformatics Players/Suppliers Profiles and Sales Data ..

Additionally Company Basic Information, Manufacturing Base and Competitors list is being provided for each listed manufacturers

Market Sales, Revenue, Price and Gross Margin table for each product type which include , Product Type I, Product Type II & Product Type III

Bioinformatics Manufacturing Cost Analysis

Bioinformatics Key Raw Materials Analysis

Bioinformatics Chain, Sourcing Strategy and Downstream Buyers, Industrial Chain Analysis

Market Forecast (2018-2023)

..and more in complete table of Contents

For More Information or Query or Customization Before Buying, Visit at https://www.databridgemarketresearch.com/checkout/buy/singleuser/north-america-bioinformatics-market

Key questions answered in this report

What will the market size be in 2026 and what will the growth rate be

What are the key market trends?

What is driving Bioinformatics Market?

What are the challenges to market growth?

Who are the key vendors in Market space?

What are the key market trends impacting the growth of the Bioinformatics Market ?

What are the key outcomes of the five forces analysis of the Bioinformatics Market?

What are the market opportunities and threats faced by the vendors in the Bioinformatics market? Get in-depth details about factors influencing the market shares of the Americas, APAC, and EMEA?

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Data Bridge Market Research set forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process.

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Bioinformatics Market 2020 Climbs on Positive Outlook of Booming Sales| Illumina, NAnexus, Qiagen, Thermo Fisher Scientific - News Times

Feb. 13, 2020 06:00 UTC

CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)-- Foundation Medicine, Inc. and Chugai Pharmaceutical, Ltd. (TOKYO: 4519) have entered into an agreement with the National Cancer Center (NCC) for the use of FoundationOneLiquid, Foundation Medicines laboratory-developed liquid biopsy test, in the third stage of SCRUM-Japan, the largest cancer genomic screening consortium in Japan. The multinational program provides genomic screening in collaboration with hospitals on a regional scale in Japan and other countries in Asia, and aims to accelerate the development of innovative biomarker-driven precision medicine cancer therapies.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200212005980/en/

The third stage of SCRUM-Japan is structured in two programs LC-SCRUM-Asia and MONSTAR-SCREEN. LC-SCRUM-Asia is investigating genomic changes with the aim of delivering precision medicine to lung cancer patients. MONSTAR-SCREEN is investigating genomic changes across all types of advanced solid tumors, expanding beyond gastrointestinal cancer which was the focus of the second stage.

The SCRUM-Japan program is a model of how collaboration between industry and academia is making precision medicine a reality for people in need of new treatment approaches, said Brian Alexander, chief medical officer of Foundation Medicine. Utilization of FoundationOne Liquid in this program underscores its value in informing potential therapy selection for advanced-stage cancer patients. We look forward to continuing to expand access to comprehensive genomic profiling through this collaboration.

SCRUM-Japan is a groundbreaking program to find therapies for patients with advanced cancer. There is an increasing need for blood-based genomic testing in patients who cannot give tissue samples, including those who are unable to undergo invasive tumor biopsy, said Dr. Minoru Watanabe, vice president, head of Chugais Foundation Medicine Unit. We believe that this collaboration with the NCC, which has led genomic screening in Japan, will pave the way to realize true precision medicine across the country.

With the aim of delivering optimal treatments to patients, SCRUM-Japan was started with a view to detect cancer genomic alterations. The important achievements we saw from the first two stages include registration of over 10,000 patients clinical and genomic data, and approval of five therapeutic drugs and six in vitro diagnostics products based on clinical studies conducted by utilizing the data, said Atsushi Ohtsu, M.D., Ph.D., director of National Cancer Center Hospital East and Representative of SCRUM-Japan. Cancers remain leading causes of deaths in Japan and lung cancer has been ranked as the first leading cause of death among all cancer types. By incorporating FoundationOne Liquid into LC-SCRUM-Asia and MONSTAR-SCREEN, we believe the third stage of SCRUM-Japan will further prove the benefit of comprehensive genomic profiling tests such as FoundationOne Liquid.

Lung and gastrointestinal cancers are among the leading causes of cancer-related deaths in Japan, accounting for over 72 percent of cancer deaths in 2018, according to the World Health Organization. Through this collaboration, Foundation Medicine and Chugai will provide FoundationOne Liquid to academic centers participating in LC-SCRUM-Asia and MONSTAR-SCREEN.

In April 2018, Foundation Medicine received Breakthrough Device Designation from the U.S. Food and Drug Administration (U.S. FDA) on a forthcoming version of Foundation Medicines liquid biopsy test, which is currently under U.S. FDA review. Chugai and Foundation Medicine are preparing for the regulatory filing of this version of the test in Japan with the intention that the product will be approved for use under the National Health Insurance coverage in Japan. The parties intend that both LC-SCRUM-Asia and MONSTAR-SCREEN will transition from the existing FoundationOne Liquid test to the forthcoming version of Foundation Medicines liquid biopsy test following its anticipated approval by the U.S. FDA and subject to the terms of the agreement.

About SCRUM-Japan SCRUM-Japan is the largest cancer genomic screening consortium in Japan and aims to accelerate the development of innovative biomarker-driven precision medicine cancer therapies. Since its launch in 2015, more than 10,000 patients with advanced cancers have participated in SCRUM-Japan. The third stage of SCRUM-Japan started in June 2019, and includes two programs LC-SCRUM-Asia and MONSTAR-SCREEN. LC-SCRUM-Asia is investigating genomic changes with the aim of delivering precision medicine to lung cancer patients. More than 200 hospitals in Japan and Taiwan have joined the program and its scope area is expanding across Asia. MONSTAR-SCREEN is investigating genomic changes across all types of advanced solid tumors including gastrointestinal cancer. 28 hospitals have registered in Japan, and it aims for patients with various types of cancer to participate in the program.

About Foundation Medicine Foundation Medicine is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient's unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patients cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicines molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visit http://www.FoundationMedicine.com or follow Foundation Medicine on Twitter (@FoundationATCG).

About Chugai Chugai Pharmaceutical is one of Japans leading research-based pharmaceutical companies with strengths in biotechnology products. Chugai, based in Tokyo, specializes in prescription pharmaceuticals and is listed on the 1st section of the Tokyo Stock Exchange. As an important member of the Roche Group, Chugai is actively involved in R&D activities in Japan and abroad. Specifically, Chugai is working to develop innovative products which may satisfy the unmet medical needs.Additional information is available at https://www.chugai-pharm.co.jp/english/.

Foundation Medicineand FoundationOne are registered trademarks of Foundation Medicine, Inc.

Source: Foundation Medicine

View source version on businesswire.com: https://www.businesswire.com/news/home/20200212005980/en/

See the article here:

Foundation Medicine and Chugai Announce Partnership with National Cancer Center for the Use of FoundationOneLiquid in the Third Stage of SCRUM-Japan -...

Ive been committed to understanding the biology of aging since I was a teenager, and my education and career took aim at this problem from many angles. One aspect that still perplexes me is that there isnt a good, easily communicable answer to this simple question: What is biological aging?

When it comes to biological aging research or, to use a fancier term, translational geroscience, scientists finally have a pretty good understanding of the major components of aging. But theres no consensus definition of it that consolidates the existing framework.

Why do we need such a definition of biological aging? A good definition can grab the essential characteristics of an entity and put them to good use. Two examples illustrate this.

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Here is an example from medicine, published this month in Nature: Cancer is a catch-all term used to denote a set of diseases characterized by autonomous expansion and spread of a somatic clone. That is a more exact way of saying, Cancer is a disease caused by uncontrolled division of abnormal cells. This definition captures the universal mechanism behind all cancers. As such, it also offers therapeutic options. No matter how diverse cancers get, keeping them under one umbrella is easier compared to the broad-spectrum of biological aging.

A definition from mathematics is also instructive: The derivative of a function is the measure of the rate of change of the value of the function dependent on changes in the input. It is a solid definition as it offers a procedure to compute the extreme values of a function.

Here are three consecutive steps empirical, philosophical, and computational that can be taken to create a good definition of biological aging:

The empirical step involves collecting what is already out there. Over the years, researchers have invented their own idiosyncratic definitions of biological aging, though these generally miss parts of the story.

Scientists often start papers with a summary referring to the consensus knowledge in the field and then ask the particular question they want to address and highlight the results. These summaries, which often contain definitions, are important educational windows into science, used by mainstream media to publicize results and form relevant narratives.

To illustrate the empirical step, I extracted four definitions from scientific papers exploring different aspects of aging that reveal the conceptual mess around defining biological aging.

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death came from a 2013 paper in the journal Cell by Carlos Lpez-Otn and colleagues.

Aging underlies progressive changes in organ functions and is the primary risk factor for a large number of human diseases was the definition in a 2019 report in Nature Medicine by Benoit Lehallier and colleagues.

Aging is a progressive decline in functional integrity and homeostasis, culminating in death was used in a 2019 review of the genetics of aging in Cell by Param Priya Singh and colleagues.

Finally, a 2020 paper in Nature Medicine on personal markers of aging by Sara Ahadi and colleagues offered this: Aging is a universal process of physiological and molecular changes that are strongly associated with susceptibility to disease and ultimately death.

I analyzed several components of these definitions of biological aging, as indicated by the column headers in the table below, and identified some recurring themes. The final column indicates logical connections between these components.

This analysis offers two lessons, one negative and one positive. The negative lesson is that some definitions have hardly any overlap, as seen in I and II its apples and oranges. The positive lesson is that the recurring themes suggest the possibility of creating a core definition for biological aging using a bottom-up, empirical approach by analyzing many attempted definitions.

However, I dont believe that such a process would be sufficient.

The myriad definitions of biological aging help identify some necessary components of it. But an aggregated mash-up wont guarantee a formally correct and useful definition. Identifying the content itself is not enough, especially when dealing with such a complex and lifelong process. Just because we have found most of the puzzle pieces does not mean we can put the puzzle together without a clue to its shape.

This is where the philosophical step comes into the picture. Here, biologists will benefit from recruiting people trained to come up with a formal definition: philosophers, mathematicians, computer scientists, and the like.

The philosophical step involves identifying a list of criteria that a consensus definition of biological aging should meet. I believe that such a definition should meet at least these five criteria:

Completing the empirical and philosophical steps would yield a good starting point for a well-formed definition that captures the essentials of biological aging.

A consensus definition that meets both content and formal criteria, achieved through the empirical and philosophical steps, might help stabilize not just scientific consensus but consensus on public policy. Here the main issues are the relationship between biological aging and disease; and regulatory, clinical, and social aspects of healthy longevity. But a completed computational step will give us actual tools, helping the biomedical technology that advances healthy lifespans.

Applicability is perhaps the most important feature of a good definition, and this where the computational step comes in. The definition should suggest future experiments and, even more important, lend itself to computability so a formal model of biological aging can be built from it. Such a model can be used to simulate and compute biological aging scores based on input data and assess the effects of planned or real interventions to slow or stop negative aging processes.

Biomedical researchers now have a solid core of knowledge on biological aging, but do not have a working consensus definition to consolidate and represent this core knowledge and capture this so far elusive life process. The lack of an unambiguous and computable formal consensus definition of biological aging severely limits the applicability of this core knowledge to design comprehensive interventions to slow or stop negative aging processes.

A confident answer to the question What is biological aging? in humans will help us ensure that complexity does not hide any magical mysteries. Controlling that complexity to maximize a healthy lifespan wouldnt need a magic wand, either.

Attila Csordas is a longevity biologist and philosopher and the founding director of AgeCurve Limited, based in Cambridge, U.K.

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We need to take steps toward building a consensus definition of biological aging - STAT

Hollywoods usual version of a death scene differs greatly from reality. But not when, in the old western movie, a cowboy is hit by an Indian arrow. Hes immediately handed a bottle of whisky, takes a few swigs of it, and the arrow is pulled out. The use of alcohol to decrease the effects of pain is as old as the fermentation process. But whats the magic ingredient in alcohol that works so well?I decided to try and find out from scientific sources. Read on, too, for my latest experience with medical marijuana (cannabis).

Trevor Thompson, professor at London, Englands Greenwich University, reports 18 different studies tested the reactions of over 400 people to evaluate the painkilling aspects of alcohol. They were exposed to cold, heat, and pressure, both with and without the influence of alcohol.

Thompson concluded that two beers relieved pain by 25%. He added that this provided more relief than opioid drugs such as codeine, and even more than that obtained from paracetamol (Tylenol). So the study concluded that there is robust evidence that alcohol is an effective painkiller. Moreover, as one might suspect, the higher the level of alcohol in the blood, the greater is the relief of pain.

Researchers at the University of Aberdeen, Scotland studied the effects of alcohol on 2,200 people who suffered from fibromyalgia and other painful chronic conditions. This study showed that the heaviest drinkers, those who consumed three to five drinks daily, were 67 percent less likely to experience pain than non-drinkers.

Another study carried out in Sweden and published in the British Medical Journal showed an interesting finding. Women who had three drinks a week had half the risk of developing rheumatoid arthritis than teetotalers.

These scientific results match everyday common sense. After all, weve all seen drunks who, while drinking to excess, get injured in the process. Yet theyre completely unaware of their injuries until they sober up.

It is disheartening to hear from readers who suffer from chronic pain. One wrote to me, Its suicide or drinking. But frankly, I prefer death. Another, half in jest, said, All my blessings come from God and good bourbon. Yet we know that drinking away your pain is not the answer.

So is there truly an ingredient in alcohol that can relieve soul-searching pain? Its not easy to find out. Trevor Thompson concluded, I hope that in the future drug producers are able to isolate specific compounds found in alcohol that provide the analgesic effects without the harmful effects of alcohol.

Id say Amen to the discovery of a pain-relieving molecule in alcohol. It would be a great bonanza to relief of human suffering, and the discovery should be awarded the Nobel Prize in Medicine.

Today, patients have access to an abundance of painkillers. Unfortunately they all come with side-effects. Each year thousands of people are killed from an overdose of opioid drugs. These painkillers are also associated with disabling constipation. Sadly, it remains the best kept secret that a starting dose of 2,000 milligrams (mg) of powered vitamin C, with an increasing dose of 2,000 mg every night, always produces good results. This natural remedy, available in health food stores, is overlooked while many people continue using over-the-counter laxatives that injure bowels.

So whats my latest experience with medical cannabis? I recently believed Id finally found a cure for chronic neck pain. Previously I had experimented with various brands of medical cannabis, such as oral oils and rub on creams. I may as well have been using water.

But then a cannabis producer announced the use of nanotechnology to produce medical cannabis. This means cannabis ingredients are reduced in size to penetrate the body easier. The result is an increased dose of cannabis directed to the area of pain.

The result? Unfortunately, it was another medical cannabis failure for me. But there is some good news. Its getting close to five oclock and a glass of Chardonnay with dinner beats all the medical cannabis Ive tried.

Surely theres a brilliant molecular scientist somewhere to find the magic pain molecule in alcohol.

Dr. Ken Walker (Gifford-Jones) is a graduate of the University of Toronto and The Harvard Medical School. He trained in general surgery at the Strong Memorial Hospital, University of Rochester, Montreal General Hospital, McGill University and in gynecology at Harvard. He has also been a general practitioner, ships surgeon and hotel doctor. Sign up for medical tips at docgiff.com, and take a look at the new web site.

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Dr. Gifford-Jones: Whats the magic painkiller in alcohol? - MPNnow.com

PHILADELPHIA The Bmal1 gene, found throughout the human body, is believed to be a critical part of the bodys main molecular timekeeper, but after deleting it in animal models, researchers from the Perelman School of Medicine at the University of Pennsylvania found that tissues continued to follow a 24-hour rhythm. The team also found these tissues could follow that circadian rhythm the 24-hour molecular clock that influences a variety of daily functions from sleep to metabolism even in the absence of outside stimulus that can influence the cycle, like light or temperature changes. These results indicate that, while the Bmal1 gene may heavily influence some circadian rhythm, the process is controlled by a more complex system, and that other drivers of the biological clock exist. The research published this month in the journal Science.

Using skin fibroblasts and liver slices from mice, tissues that are regularly part of circadian rhythm research, Penn researchers deleted Bmal1 and isolated the tissue from light, temperature, and other outside factors that trigger 24-hour activities. Even in that condition, the tissues still showed normal 24-hour oscillations or circadian reactions for two to three days at the gene and protein level of cells. The finding shows that current understanding of circadian rhythms is not complete and lays the groundwork for researchers to shine a spotlight on approximately 30 specific genes and proteins that appear to function regularly with or without the Bmal1 gene.

Circadian rhythms are really a hierarchical system in our bodies, and the Bmal1 gene appears to be important for making the brain clock tick. This brain clock is in a place called the suprachiasmatic nucleus, and is like the conductor of an orchestra, said Akhilesh B. Reddy, MA, MB, BChir, PhD, a professor of Pharmacology at Penn. We found that, surprisingly, if you remove the conductor (by deleting the Bmal1 gene), the musicians the tissues in the body can continue to keep playing at their own 24-hour tempo. So while an active conductor does influence and guide the orchestra, the absence of the conductor doesnt mean that all circadian processes fail to take place. The tissues and cells in the body (the musicians) still have natural rhythm.

Many tissues are affected when normal sleep patterns arent followed, and therefore the circadian rhythm is disturbed. Skin cells require sleep in order to perform vital repairs. People who work night shifts, often change shifts, or frequently travel may experience changes to their metabolism, leading to glucose intolerance and may, over time, develop type-2 diabetes. And while the reason is not clear, women who work night shifts have an increased likelihood of developing breast cancer.

Cells throughout our bodies are performing certain functions during wake hours and others during sleep hours, Reddy said. Uncovering all the specific molecular mechanisms that influence circadian rhythms is imperative in order to develop treatments targeting the health issues that arise when the rhythm is altered, like in shift work.

In the near future, Reddy and his colleagues plan on investigating the 30 or so specific proteins they found that can operate with or without Bmal1s presence.

While the results suggest our understanding of molecular circadian rhythms as a scientific community is incomplete, were excited to now move closer to a fuller understanding of previously unknown processes that control our bodies internal clocks, said Reddy.

This work was performed in collaboration with Penns Institute for Translational Medicine and Therapeutics. Additional Penn authors include Sandipan Ray and Utham K. Valekunja.

This study was supported by the European Research Council (281348, MetaCLOCK), the EMBO Young Investigators Programme, the Lister Institute of Preventive Medicine, a Wellcome Trust Senior Fellowship in Clinical Science (100333/Z/12/Z), and also the Francis Quick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust (FC001534).

Originally posted here:

Results from a new study suggest that Bmal1 gene is not an essential regulator of circadian rhythms - Mirage News