One of the goals of COVID-19 research is understanding why some people develop mild or moderate cases while others experience life-threatening illness. Researchers have made progress in understanding some of the factors that make a difference, including obesity and underlying health conditions like diabetes and heart disease.

Recently, an ongoing study by European scientists has suggested one more potential factor to consider: blood type. Preliminary results of this investigation (which have not yet been peer reviewed) were shared on June 2 on the preprint service MedRxiv.

The researchers scrutinized blood samples from 1,610 hospitalized patients in Italy and Spain with the disease, as well as a 2,205 healthy people in a control group. Their analysis identified variations at two distinct areas on the genome (the complete set of human DNA, including all genes) that were associated with greater risk for severe reactions toSARS-CoV-2, the virus that causes COVID-19, including respiratory failure.

One of these areas on the genome is related to blood types. The researchers found that type A blood was associated with a 50 percent increase in risk that a patient would become extremely ill with COVID-19 and need supplemental oxygen or a ventilator.

This conclusion supports findings from early research done in China, which appeared March 27 in MedRxiv. This gave the researchers more confidence in the associations, says study coauthor Andre Franke, PhD, professor of molecular medicine at the Institute of Clinical Molecular Biology at University Hospital Schleswig-Holstein in Kiel, Germany.

Researchers on another ongoing study, by genetic testing firm 23andMe, released preliminary data on June 8 suggesting that type O blood is protective against COVID-19. The researchers found that people with type O blood are between 9 and 18 percent less likely to test positive for COVID-19 than other blood types.

The 23andMe study is still recruiting subjects, but already has 750,000 participants and is likely to come out with more data regarding genetic associations and COVID-19.

RELATED: The New Normal: What We Know About the Coronavirus So Far and How We Got Here

Dr. Franke hopes to build on the findings about type A blood withmore targeted research, he says, especially because there are 36 known human blood groups. In addition to the four main types A, B, AB, and O there is also a deeper classification system that includes different combinations of antigens (molecules on the surface of every red blood cell) and other substances.

There are other types of diseases where blood types and blood groups affect a persons susceptibility. For example, people who lack a specific type of antigen, called a Duffy antigen, have a higher resistance to malaria.

In terms of why a variant like the gene related to blood type would have significance for COVID-19, Franke says there are three possible hypotheses.

One is that the genetic variant itself contributes to the so-called cytokine storm, in which a persons immune system goes into overdrive in response to the novel coronavirus threat, releasing large amounts of pro-inflammatory substances called cytokines. An excess of cytokines can damage healthy tissues.

The second hypothesis is that the genetic variant causes more coagulation (blood clotting) in response to the coronavirus an already observed result of disease progression.

The third theory is that both of these reactions are occurring simultaneously.

There may be other issues at play here, but given the way we know COVID-19 works, these seem the most likely reasons, Franke says. Next steps are to dig deeper into the blood groups system and see if we can pinpoint actual disease causes.

RELATED: What People With Heart Disease Need to Know About COVID-19

What should you do in response to these studies, considering you can't change your blood type? Nothing yet. Theres no need to get to a doctor if youre type A, and on the flip side, theres no reason to relax your precautions against coronavirus transmission like social distancing and hand-washing if youre type O.

Keep in mind these are preliminary results and more research needs to be done to understand how genetic variations truly affect COVID-19.

More than anything, its a nod toward how much we have left to learn about the way this virus operates, and how genetic variants may affect why some people end up in the ICU and others have milder symptoms or even none at all, says Priya Duggal, PhD, director of the genetic epidemiology program at Johns Hopkins Bloomberg School of Public Health in Baltimore.

If we can find genes that may explain some of the risk or protection from this infection, it will give us insight into the mechanism of disease, she says.

If genetics studies help us better understand how COVID-19 affects the body, they may eventually help lead to treatments.

This genetic study is hopefully the first of many that will help us to elucidate disease mechanism, susceptibility to infection, and maybe even antibody response, says Dr. Duggal. That could provide potential targets for therapeutics. We have a lot to learn from this point, but were gaining more insight with every study.

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Blood Type and COVID-19 Risk - Everyday Health

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Foundation Medicine, Inc., today announced that the U.S. Food and Drug Administration (FDA) approved FoundationOneCDx as a companion diagnostic for KEYTRUDA (pembrolizumab), Mercks anti-PD-1 therapy, which was also approved under accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. FoundationOne CDx is the first and only FDA-approved companion diagnostic to measure TMB and help identify patients who may be appropriate for treatment with KEYTRUDA, regardless of solid tumor type.

TMB is a measure of the number of somatic mutations per coding region within a tumors genome.1 This genomic signature can help determine a patients likelihood to respond to immunotherapies. FoundationOne CDx, Foundation Medicines comprehensive genomic profiling (CGP) assay approved for all solid tumors, enables oncologists to identify TMB-H patients ( 10 mutations/megabase) with unresectable or metastatic solid tumors across all tumor types who could potentially benefit from KEYTRUDA.

Immunotherapy is revolutionizing cancer treatment. Not only does this approval mean that clinicians will be able to identify more patients who could benefit from this treatment option, but its an important milestone in the shift toward making biomarker-driven, tumor agnostic therapies available to patients, which is possible through an FDA-approved companion diagnostic, said Brian Alexander, M.D., M.P.H., chief medical officer at Foundation Medicine. Were proud to have been at the forefront of efforts to bring TMB from research into clinical practice in partnership with the oncology community. Its exciting to see this breakthrough translate into advanced care for patients.

FoundationOne CDx is the first FDA-approved CGP test that is clinically and analytically validated for all solid tumors and incorporates multiple companion diagnostic claims. It is currently approved as the companion diagnostic test for more than 20 therapies across multiple cancer types.

This approval represents a paradigm shift toward biomarker-driven cancer treatment. Its made possible in part by an unparalleled collaboration to better understand how TMB levels are measured and reported, said Jeff Allen, President and CEO of Friends of Cancer Research. TMB provides an additional tool to inform clinical care, especially for cancer patients previously ineligible for immunotherapy based on existing biomarkers.

Merck also announced today that the FDA approved its supplemental Biologics License Application (sBLA) for KEYTRUDA, for adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. The accelerated approval was based on a prospectively planned and retrospective analysis of the KEYNOTE-158 open-label trial, which used a clinical trial assay (CTA) based on FoundationOne CDx to determine TMB status in patients tumor tissue. The results showed that patients with TMB-H in solid tumors ( 10 mutations/megabase) who were treated with KEYTRUDA had a higher overall response rate (29%) compared to patients with TMB <10 mut/Mb (6%).2

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is now approved for two pan-tumor indications. In 2017, KEYTRUDA was granted FDA approval as the first cancer treatment based on a genomic signature, regardless of cancer type, in microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. More information about KEYTRUDA can be found at http://www.keytruda.com.

About FoundationOne CDx

FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit http://www.F1CDxLabel.com.

About TMB

Tumor mutational burden (TMB) is a measure of the total number of mutations per coding area of a tumor genome.3 TMB is an additional genomic signature, similar to a biomarker, that can help identify more candidates likely to benefit from immunotherapy across a range of tumor types. Levels are measured by the number of non-inherited mutations occurring per megabase (1 million DNA base pairs) of the tumor genome.4 TMB-H tumors may be more likely to respond to certain immunotherapies because their high number of mutations make them easier for the immune system to identify. Higher TMB levels are correlated with higher levels of neoantigens, which help the immune system recognize and attack cancer cells.5 TMB can be measured with both tissue and blood-based comprehensive genomic tests.

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).

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

KEYTRUDA is a registered trademark of Merck.

Source: Foundation Medicine

1 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.2 Marabelle et al. Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253)3 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.4 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.5 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.

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FoundationOneCDx Receives FDA Approval as the First Companion Diagnostic to Identify Advanced Cancer Patients with Solid Tumors that are Tumor...

A trio of researchers at UMass Medical School in Worcester are attacking the coronavirus pandemic from three different angles, as part of a $17-million Massachusetts effort to help the world combat the disease which has killed more than 400,000 people globally.

Dr. Jeffrey Luban, a professor of molecular medicine at UMass Medical School

The researchers Dr. Robert Finberg, Dr. Ann Moormann, and Dr. Jeffrey Luban are studying ways to treat COVID-19, understand how it spreads, how people can be immune from its effects, and how herd immunity can be achieved.

We would like to know a little bit more about exactly how the virus causes the damage that it does, Finberg said.

The three UMass Medical School researchers are part of the Massachusetts Consortium on Pathogen Readiness, known as MassCPR, which is a statewide initiative including scientists and clinicians from Harvard University, the Massachusetts Institute of Technology, Boston University, Tufts University, University of Massachusetts, and local biomedical research institutes.

MassCPR is working to develop the infrastructure to address the COVID-19 pandemic. It was created through a research agreement between Harvard and the Evergrande Group in China, which is sharing financial support equally between Massachusetts research and researchers at the Guangzhou Institute of Respiratory Health in China. The funding is for five years.

MassCPR has obtained roughly $16.5 million to support and fund this first round of initiatives and projects. After receiving more than 400 applications for funding in March, MassCPR chose more than 60 applicants to receive funding, including the three at UMass.

This was obviously a very stiff competition, so anyone who actually received funding had an amazing application, said Professor David Golan from Harvard Medical School, one of the faculty co-leads of MassCPR.

According to UMass Medical School, projects selected were for their potential to influence clinical outcomes within the next 12 months. Luban, for example, a professor of molecular medicine at UMass Medical School, is researching the virologic mechanisms of COVID-19, attempting to discover what makes it unique. He aims to precisely understand infectiousness of coronavirus with his research.

Finberg, chair of the UMass Department of Medicine, is researching how to identify and target host cells and genes crucial in addressing the COVID-19 pandemic. His background in studying respiratory viruses makes researching COVID-19 a natural shift.

Dr. Robert Finberg, chair of the UMass Medical School Department of Medicine

The questions I was interested in are one, whether we can find a drug to treat the virus and the other was to find out exactly what cells the virus infects and what kind of cells respond to the virus, Finberg said in a phone interview.

His project funded by MassCPR focuses on specifically these two parts, how disease is caused and if there could be a viral treatment. Finberg does this through studying human samples.

Infectious disease can be defined in what cells the virus infects and what the host response is both cause disease, said Finberg.

Other than looking at the possibility of an antiviral agent to treat COVID-19 and how exactly the disease is caused, he is trying to understand how the virus works inside the body.

Part of Dr. Finbergs research has to do with finding so-called host targets that could be potentially drug targets that could help to prevent the infection of cells by the coronavirus, said Golan.

Moormann, a professor at UMass Medical School who focuses on infectious diseases and immunology, is looking into one of the most popular current research topics in relation to COVID-19, functional antibodies, which help the body fight off the disease.

Dr. Ann Moormann, a professor at UMass Medical School

Her study measures the spectrum of functional antibodies, how long these antibodies last for, and how they differ in people of different ages. Antibodies indicate past infections.

Part of the research I have funded is to look at the question of how long do the immunities to the virus that causes COVID-19 last, said Moormann.

Though looking at human samples to see how many antibodies currently exist in a person is part of this project, her research has a more longitudinal element where she looks at how the antibodies change over months, getting samples three, six, and nine months after the initial sample.

You can have an immune response that only protects you for a certain period of time, and it might be because your immune response doesnt become a memory response but it helps clear the infection We dont know how long [COVID-19 antibodies] last, said Moormann.

Moormann gets samples from patients who have recovered from coronavirus but also from people who were not diagnosed. She recruits study participants that are healthy and that are patients. She then tests to see whether or not the individual has antibodies.

Participants can choose to give a sample once, or, for those who want to be in the longitudinal part of the study, choose to come back in the following months to give more samples.

I want to look beyond [a few months]. Like in six months, in nine months, do you still have antibodies? Are you still protected? Moorman said.

Her research is a necessary part of understanding if and how herd immunity can be achieved to stop the COVID-19 pandemic.

Moormanns research is one of the very hottest topics right now in thinking about the pandemic, Golan said.

Its incredibly important for two reasons. One is when people get coronavirus infections, they develop the antibodies and its a question whether those antibodies protect you against another infection of coronavirus, said Golan.

Each of these doctors research projects aims to understand COVID-19 better so they are able to correctly fight against it which is why they obtained crucial funding from MassCPR.

MassCPR has been able to create a community of researchers and scientists in Massachusetts that have come together to better understand and control coronavirus. Golan said the collaboration and sharing of data between researchers is a key part of MassCPR and is already leading to important findings.

One thing that has been hugely highlighted by this pandemic is that we werent too well prepared for it, Golan said. Its our obligation to the next generation to be ready for the next one in a better way.

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Three UMass Medical School researchers are studying ways to stop, treat and protect against COVID-19, as the disease continues to kill worldwide -...

The World Health Organization caused widespread confusion and drew sharp criticism from health experts after one of its officials said recently that asymptomatic transmission of the novel coronavirus was very rare then walked back the remarks the next day.

Maria Van Kerkhove, the WHOs technical lead on COVID-19, had said nations that have conducted contract tracing studies are not finding secondary transmission onward [from asymptomatic cases]. Its very rare, The Washington Post reported.

She later clarified the comments during a live Q&A, saying that she had been referring to a small number of unpublished studies when she answered a reporters question and was not stating the policy of WHO, adding that much more research is needed.

So where do health experts stand on asymptomatic transmission? Heres what you need to know.

Health experts dont know for sure how many people have COVID-19 but dont show symptoms. But they have come up with estimates using models and available data.

In the Q&A, Van Kerkhove said WHO estimates that 6% to 41% of patients are asymptomatic, with a point estimate a single value given as an estimate of a parameter of a population of 16%.

But the U.S. Centers for Disease Control and Prevention has put its estimates somewhat higher. Based on data available before May 1, the CDC estimates 35% of cases may be asymptomatic, which is a 10% jump from the 25% estimate CDC Director Robert Redfield floated in March.

Dr. Anthony Fauci, the countrys top infectious diseases expert and the director of the National Institute of Allergy and Infectious Diseases, has given estimates closer to the CDCs numbers. He told ABCs Good Morning America that the number may be between 25% and 45%.

Other studies have found estimates within the CDCs range: A review paper published in early June in the Annals of Internal Medicine found that between 40% and 45% of patients dont have symptoms but noted that the data used to conduct the review had limitations.

Health experts say its hard to know for sure how many people are asymptomatic because many arent likely to get tested if they arent feeling sick. Individuals who contract the virus but dont show symptoms are more likely to be younger people with no underlying health conditions, health experts have said. And if their only symptoms are mild, such as feeling more tired than usual, they probably wont attribute them to COVID-19.

WHO health experts said its more important to focus on symptomatic cases first to slow the spread because most known transmissions have happened when people show symptoms, and because many nations still dont have the widespread testing capabilities needed to identify asymptomatic cases.

We have to focus our testing on those who we need to test most: health workers, people in long-term care facilities, people who are clinically unwell with the disease, said Mike Ryan, executive director of WHOs Health Emergencies Programme. I think there is much to be answered on this, there is much that is unknown. But we know enough to support the strategies that have already been put in place and continue with those strategies.

Its possible a person who isnt showing symptoms isnt passing the virus on to others, health experts say.

Besides the question of how many infected patients are asymptomatic, researchers are also trying to figure out what proportion of asymptomatic patients go on to make others sick.

Whatever proportion of the disease is transmitting from asymptomatic individuals, that is unknown, Ryan said. And that is occurring, Im absolutely convinced that that is occurring. The question is how much?

In guidance posted on its website earlier this month about the use of face masks, WHO states that evidence indicates that asymptomatically infected individuals are much less likely to transmit the virus than those who develop symptoms.

But other estimates indicate its much more common the CDC estimates that about 40% of transmissions occur before people show symptoms.

One study published in Nature Medicine in mid-April found that 44% of patients are infected by people who didnt have symptoms. And The New York Times previously reported that researchers in Hong Kong found that between 20% and 40% of infections in China may have happened before symptoms appeared.

The Annals of Internal Medicine paper found that based on patients in Iceland, Indiana and Italy, the rate of asymptomatic transmission could be as high as 45%. But the authors of that paper said that the data used in the paper are imperfect in many ways and that an ideal study of asymptomatic SARS-CoV-2 infection has yet to be done.

We simply dont know how much asymptomatic transmission happens, Eric Topol, a professor of molecular medicine at Scripps Research and one author of the study, told The Washington Post. Sometimes its important to just say that.

Health experts say its important to note that some definitions of asymptomatic include people who are pre-symptomatic or who dont show symptoms initially but later get sick.

The CDCs estimate, which says 35% of people may be asymptomatic, includes individuals who are pre-symptomatic, and the CDC has said people may be able to transmit the disease up to 48 hours before they begin showing symptoms. Some studies also include pre-symptomatic cases when estimating asymptomatic rates.

Van Kerkhove previously told ProPublica that the WHO has found few truly asymptomatic cases, or people who never show any symptoms throughout the course of the illness.

But some health experts say differentiating between the two only creates more confusion.

Its debating semantics because in a practical sense, there is no difference between people who simply havent developed symptoms yet and are infecting others, and those who are truly asymptomatic, Monica Gandhi, an infectious disease expert at the University of California at San Francisco, told The Washington Post. It looks the same in the early stages.

Ultimately, health experts say the most important thing for the public to know isnt the specific numbers. People need to understand that asymptomatic transmission does happen and that its important to take precautions as if you and those around you may be infected.

You can be vertical and feel 100% or virtually 100% and going about your daily business and unaware that youre infected and perfectly capable of transmitting the virus, Dr. William Schaffner, a Vanderbilt University professor and CDC adviser, told CNN. How do we inhibit transmission of the virus by these people who are doing their full range of normal activities? The answer is social distancing and wearing masks and good hand hygiene and stay away from crowds. Thats the formula.

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Here's what you need to know about asymptomatic transmission and COVID-19 - The Dallas Morning News

Around the world, supercomputers have been furiously poring over drug compounds to see if any of them could effectively inhibit COVID-19s insidious spike proteins, which give the virus both its crown-like appearance and its ability to enter human cells. Now, researchers from the University of Alabama in Huntsville (UAH) are leveraging supercomputing power to tackle a similar question but this team is looking specifically at naturally occurring compounds.

The researchers, led by Jerome Baudry (a molecular biophysicist at UAH), used molecular docking simulations to examine how 50,000 different natural products interacted with COVID-19s key proteins. To assess these tens of thousands of candidates, the researchers partnered with HPE, which provided supercomputing resources. Specifically, the researchers used HPEs Sentinel system a Texas-based Cray XC50 supercomputer with around 2,000 cores that is cloud-accessible via Microsoft Azure.

With the computing power in-hand (or rather, in-cloud), the researchers were able to complete 20,000 molecular dockings in just eight minutes (down from 24 hours), allowing for 1.2 million more dockings per day. The docking simulations yielded 125 natural products or close derivatives across plants, fungi, the sea and microbes that possess chemical elements which bind to key proteins on COVID-19. The identified substances span the world, including chemicals found in traditional medicine in regions like Southeast Asia and the Andes in South America. Mesua beccariana, the source of one of the candidate substances, has traditionally been used to treat fever, dyspepsia and other conditions in Malaysia. These candidates will now progress to the next stages of preliminary drug development.

The combination of the powerful supercomputing technology and expertise from HPE, molecular docking methodology, and a large, diverse data-set of natural products, is what makes this research truly unique, Baudry said. We predicted a range of natural products that can now move forward in clinical drug testing, some of which can be found in extracts that come from organisms that grow in our backyards, and some that can only be discovered in remote areas of the world such as in jungles or in the deep sea. We are inspired by these results and it is only the beginning of our journey to unlock more insight that will bring us even closer to conquering COVID-19.

The results arent, of course, a silver bullet.

None of these natural products are expected to single-handedly be used as a treatment or cure to COVID-19, Baudry said. Instead, it is the combination of the chemical structures from this list that are beneficial to drug testing to develop a treatment.

The researchers are also adamant that overeager readers not turn to self-medication.

I repeat, Baudry said, these organisms or chemicals should not be used as treatments against COVID-19.

Header image: the molecular docking simulations in action. Image courtesy of UAH.

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Natural Medicine and Supercomputing Team Up to Combat COVID-19 - HPCwire

DetailsCategory: Small MoleculesPublished on Saturday, 20 June 2020 18:09Hits: 570

MT-7117 Receives Orphan Drug Designation from FDA

JERSEY CITY, NJ, USA I June 19, 2020 I Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced that Mitsubishi Tanabe Pharma Development America, Inc. (MTDA) has initiated a Phase-3 clinical trial in the U.S. of the selective melanocortin 1 receptor (MC1R) agonist), MT-7117 (dersimelagon), an investigational oral therapy being studied as a possible treatment option to increase pain free light exposure in adult and adolescent patients with a history of phototoxicity (including severe pain on exposure to sunlight) from erythropoietic protoporphyria (EPP) or X-LinkedProtoporphyria (XLP).1

MTDA was granted Orphan Drug Designation for MT-7117 by the U.S. Food and Drug Administration on June 8, 20202, and received Fast Track Designation in June 2018.3

"Mitsubishi Tanabe Pharma group companies are working hard to advance research and development activities to deliver new therapy options that address the needs of patients fighting serious diseases," said Atsushi Fujimoto, President, Mitsubishi Tanabe Pharma America, Inc. "Through further clinical development and potential regulatory approval, this investigative oral treatment could provide another option for patients with EPP or XLP."

The global Phase-3 study (NCT04402489) is a multicenter, randomized, double-blind, placebo-controlled study to evaluate efficacy, safety, and tolerability of MT-7117 in approximately 159 people (age 12-75 years) with EPP or XLP over a 26-week treatment period.4 The primary objective of the study is to investigate efficacy of MT-7117 on time to first onset of prodromal symptoms associated with sunlight exposure in adults and adolescents with EPP or XLP.4 The Phase-3 study design will leverage experience and knowledge obtained from an earlier Phase-2 study.

The Phase-2 study (NCT03520036) was a randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of MT-7117 in 102 people (age 18-75 years) with EPP.5 The study consisted of a two-week screening period, a 16-week double-blind treatment period and a six-week follow-up period at Week 22.5

About MT-7117 (Dersimelagon)MT-7117 is a novel synthetic, orally-administered, non-peptide small molecule, which acts as a selective agonist of melanocortin-1 receptor (MC1R) with a potential for being effective to increase pain free light exposure in patients with a history of phototoxicity from erythropoietic protoporphyria (EPP) and X-Linked Protoporphyria (XLP). Mitsubishi Tanabe Pharma Corporation (MTPC) is developing MT-7117 as a potential treatment option for EPP or XLP. MT-7117 is an investigational medication and not approved by FDA or any other regulatory authority.

About Erythropoietic Protoporphyria and X-Linked Protoporphyria Erythropoietic Protoporphyria (EPP) is an inherited disorder of the heme biosynthetic pathway that results from mutations of the ferrochelatase (FECH) gene or, less commonly X-Linked Protoporphyria (XLP) that results from mutations in the aminolevulinic acid synthase-2 (ALAS2) gene.1 Both EPP and XLP are characterized by accumulation of protoporphyrin in blood, erythrocytes and tissues and cutaneous photosensitivity.1 EPP and XLP usually present early in childhood with extremely painful phototoxic reactions which are preceded by a prodrome of tingling, stinging, and/or burning of sun-exposed skin.1 The onset of prodromal symptoms after direct sun exposure varies but may occur in less than 10 minutes.6,7 Importantly, continued exposure to sunlight following the onset of prodromal symptoms will lead to phototoxicity-induced pain.8

About Mitsubishi Tanabe Pharma America, Inc.Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation's (MTPC) 100 percent owned U.S. holding company, Mitsubishi Tanabe Pharma Holdings America, Inc. MTPA is dedicated to delivering innovative products that address the unmet medical needs of patients in North America. It was established by MTPC to commercialize approved pharmaceutical products in North America with plans to expand its product line through collaborations with partners. For more information, please visit http://www.mt-pharma-america.com or follow us on Twitter, Facebookand LinkedIn.

About Mitsubishi Tanabe Pharma Development America, Inc.The U.S. headquarters of Mitsubishi Tanabe Pharma Development America, Inc. (MTDA) is located in Jersey City, New Jersey. MTDA is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation's 100 percent-owned U.S. holding company, Mitsubishi Tanabe Pharma Holdings America, Inc. MTDA is dedicated to research and develop innovative pharmaceutical products that address the unmet medical needs of patients. For more information, please visit https://mt-pharma-development-america.com/

Overview of Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma, which was founded in 1678, has its headquarters in Doshomachi, Osaka, which is the birthplace of Japan's pharmaceutical industry. With business centered on ethical pharmaceuticals, Mitsubishi Tanabe Pharma is a well-established company with one of the longest histories of pharmaceutical companies in Japan.9 In accordance with the corporate philosophy of "contributing to the healthier lives of people around the world through the creation of pharmaceuticals," the Company formulated the key concept of Open Up the Future under the Medium-Term Management Plan 2016-2020. Through the discovery of drugs that address unmet medical needs, centered on its priority disease areas immune-inflammation diseases, diabetes and kidney, central nervous system, and vaccines Mitsubishi Tanabe Pharma will strive to contribute to the health of patients around the world. MTPC is the parent company of MTPA and MTDA. For more information, go to http://www.mt-pharma.co.jp/.

1 NIH website: https://rarediseases.info.nih.gov/diseases/4527/erythropoietic-protoporphyria2 FDA website: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=645518 3 MTPC Press Release: https://www.mt-pharma.co.jp/e/release/nr/2018/pdf/e_MTPC180727.pdf4 ClinicalTrials.gov. U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT04402489 5 ClinicalTrials.gov. U.S. National Library of Medicine: https://www.clinicaltrials.gov/ct2/show/NCT03520036 6 Balwani M, Naik H, Anderson KE, Bissell DM, Bloomer J, Bonkovsky HL, et al. Clinical, biochemical, and genetic characterization of north american patients with erythropoietic protoporphyria and X-linked protoporphyria. JAMA Dermatol. 2017 Aug 1;153(8):789-96. 7 de Bataille S, Dutartre H, Puy H, Deybach JC, Gouya L, Raffray E, et al. Influence of meteorological data on sun tolerance in patients with erythropoietic protoporphyria in France. Br J Dermatol. 2016 Oct;175(4):768-75.8 American Porphyria Foundation: https://porphyriafoundation.org/for-patients/types-of-porphyria/epp-xlp/ 9 Research by TOKYO SHOKO RESEARCH, LTD.

SOURCE: Mitsubishi Tanabe Pharma America

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Phase-3 Clinical Trial of MT-7117 INITIATED IN THE US for Rare DiseaseS, Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) | Small...

JenGommerman, an immunologist at the University of Toronto, wants everyone to know one important point about the COVID-19 pandemic: The human immune system is working to fight off this novel coronavirus.

Many thousands of people have died from the virus. But many more thousands have contracted it and survived. That is because when the virus first enters your body, usually through your nose or mouth, it triggers the immune system to send antibodies in response. Antibodies are proteins in your blood that your body uses to fight infection. In diseases such as chicken pox, the antibodies usually prevent you from getting the illness again. The formal term for the generation of antibodies is a humoral immune response.

But COVID-19 the illness caused by the SARS-CoV-2 virus is puzzling scientists with some challenging questions: If a person recovers from COVID-19, will the antibodies keep that person from being infected again? Why dont some people show symptoms? What happens as soon as the virus enters the body?

Gommerman, a professor in the department of immunology in the Faculty of Medicine, has received support from the Ontario COVID-19 Rapid Research Fund to conduct research in collaboration with an interdisciplinary team of scientists to answer these and other questions.

She emphasizes that the greatest challenge in understanding anything to do with COVID-19 is the fact that it is new.

Understanding how SARS CoV-2 induces a humoral immune response is vital to scientists eventually developing a vaccine, she says. But the world has only known about this virus since December or January. It is brand new. The science community doesnt fully understand yet how the immune system responds to the virus.

So my teams work will shed some light on that, which, in turn, could help with the development of a vaccine.

The provinces rapid research fund is also supporting the work ofJean-Philippe Julien, senior scientist in molecular medicine at the Hospital for Sick Children and an assistant professor in biochemistry and immunology at U of T. His projectwill usemolecular technology to develop a potent and broad antiviral treatment.

As forGommerman, she will be developing an assay (the scientific term for a test or experiment) to identify antibodies in saliva in the hopes of better understanding the early immune response when the virus enters the oropharyngeal tract (a part of the throat behind the mouth and nasal cavity).

Like so much of the COVID-19 research being conducted now, the work being spearheaded byGommermanis a collaboration with a number of other scientists at U of T and the universitys partner hospitals.

Gommermansresearch into saliva, for example, will be compared with assays being done byAnne-Claude Gingras, a senior investigator at Sinai Healths Tanenbaum Lunenfeld Research Institute and a professor of molecular genetics at U of T.

Gingras has led the development of a blood test that can detect antibodies in the immune system of infected patients. The test has the potential to enable hospitals and other institutions to screen up to 10,000 samples at once. This type of analysis is called serosurveillance the study of blood serum, especially as it relates to the work of the immune system response to pathogens entering the body.

Serosurveillanceis an important weapon in our fight against COVID-19,Gommermansays. It has the power to tell us what is the true scope of the pandemic. This is what the blood experiments at Mount Sinai get us.

For the saliva experiments, we will learn more about what is happening early in the immune response in asymptomatic patients in the oropharyngeal tract where the virus is first introduced. This has the potential to reveal what aspects of the immune response might confer protection to those people who never show symptoms or only show mild symptoms.

Key to understanding the early immune response is a collaboration withDarrell Tan, an infectious diseases physician and clinician-scientist at St. Michaels Hospital. Tan, who is also an assistant professor in U of Ts Faculty of Medicine and at the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health, is enrolling 1,000 subjects, via contact tracing, who have been linked to patients infected with COVID-19. Tan and his team will test the saliva of these people regularly over a number of weeks.

The contacts are called a ring of associates.

Because the people in that ring have a higher chance of contracting COVID-19 than the general public, we will presumably have people who are just getting infected, saysGommerman. This will allow us to learn why some people dont show symptoms but still have the illness and how the early immune response actually works.

BothGommermanand Gingras are using proteins produced by U of TsJames Rini, professor in the departments of molecular genetics and biochemistry. The proteins are highly purified pieces of the SARS-CoV-2 virus that are used as bait to catch antibodies in the saliva or in the blood so that the researchers can measure them.

Without Jims work on these proteins, we wouldnt be able to go further in our research, saysGommerman. Hes been studying coronavirus proteins since SARS first hit North America in 2003. The science community doesnt know nearly as much about coronaviruses as we do, for example, influenza.

We owe a lot to researchers like Jim who have been building up a knowledge base about coronaviruses. Were relying on them now.

Further to the collaborative nature of the research,Gommermansteam is using saliva samples from patients who have had the virus, andwho have recovered. The samples were collected by:Mario Ostrowski, a professor in the departments of medicine, immunology and laboratory medicine and pathobiology at U of T;AllisonMcGeer, director of the Infectious Diseases Research Unit at Mount Sinai Hospital and a U of T professor in the departments of medicine and laboratory medicine and pathobiology (LMP), as well as at the Dalla Lana School of Public Health; andSamiraMubarekaan assistant professor in the department of laboratory medicine and pathobiology who is at Sunnybrook Health Sciences Centre.

The multidisciplinary nature of the research is what enabledGommermanto pivot from her usual work on autoimmune diseases, especially multiple sclerosis, and gut immunology. The ability to draw on the skills and experiences of members of her team was also key.

Our research associate, Dr.Olga Rojas, had worked on saliva antibodies to a disease called rotavirus when she was studying in Columbia, South America.

Also key to the pivot were three first-year doctoral students BaweletaIsho,Annie PuandMichelle Zuo.

I didnt want to pull more senior students from their doctoral work, so I asked these first-year students to help with the work,Gommermansays. Theyve been amazing, as well as our project manager, Dr.Gary Chao,who organized all the samples and made sure we were compliant from a biosafety and ethics perspective. This was urgent work and they all rose to the occasion under a lot of pressure.

with files from Amanda Ferguson

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How does the body fight COVID-19? U of T researcher's work could aid vaccine development - News@UofT

19.06.20

A research initiative to rapidly identify potentially game-changing Covid-19 drugs, led by the University of Liverpool, has been awarded funding of more than 2.2m.

With conventional evaluation of new medicines being a lengthy processes, typically taking upwards of 10 years, new methods have had to be adapted and developed to meet the urgent need for treating and preventing the currentcoronavirus outbreak.

Already there is a number of ongoing large-scale clinical trials testing a first wave of repurposed medicines, such as Ebola medicine remdesivir, HIV drug lopinavir and malaria treatment hydroxychloroquine, to see if they could have similar positive impacts in treating Covid-19.

Yet, should these compounds fail to demonstrate clear benefit, a more broad and increasing range of alternative compounds many with far less clinical evidence available will have to be examined. Processes like these will require an ability to rapidly provide clinical proof-of-concepts for drug candidates emerging from global pre-clinical screening efforts. Dynamic early stage (phase I/IIa) clinical trials will be required to advance, ahead of time, plausible candidates for inclusion in randomised phase III clinical trials, and to eliminate candidates with little or no prospect of clinical success before huge resources are committed.

The AGILE Covid-19 Drug Testing Initiative, which is being led by the University of Liverpool and involving researchers from the Liverpool Tropical School of Medicine, Southampton Clinical Trials Unit and NIHR Liverpool and Broadgreen Clinical Research Facility, has been established to enable the rapid clinical evaluation of potential Covid-19 therapeutics.

READ MORE:Worlds largest potential coronavirus treatments trial rolled out in UK

READ MORE:University Hospital Southampton trialling new coronavirus drug

Saye Khoo, Professor of Molecular and Clinical Pharmacology at the University of Liverpool, said: AGILE uses the most modern and innovative statistical methods which allows for multiple drugs to be tested in parallel, and to remove or add treatments faster than ever before, based on results of safety and efficacy.

This has the advantage of testing more treatments, more quickly, to find out which new drugs are suitable for large-scale testing in COVID-19 patients. This is similar to fast track programmes for treatment of cancer patients that are approved by the UK regulator.

Andrew Owen, a fellow Professor of Molecular and Clinical Pharmacology at the University of Liverpool, added: Working closely with established consortia including key stakeholders involved in WHO-led expert groups for treatment and prevention of COVID-19, AGILE will advance plausible candidates for these consortia to test in large-scale trials.

AGILE has been specifically designed to rapidly identify drugs that stand the best chance of success in the battle against COVID-19.

The AGILE clinical research trials will be taking place at the NIHR Royal Liverpool and Broadgreen Clinical Research Unit based at the Royal Liverpool University Hospital. The unit provides state of the art purpose-built facilities that offer a safe and regulated environment to perform clinical research trials to the highest possible standards.

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University of Liverpool-led initiative awarded 2.2m funding - National Health Executive

The Department of Molecular Medicine is actively engaged in research and education to build a premier virus, gene and cell therapy program and to translate promising therapeutics from bench to bedside in a timely manner.

The wide range of disciplines represented the Department of Molecular Medicine's leadership team and staff facilitates a breadth of translational activities. The researchers in the Department of Molecular Medicine are in the unique position of being able to move a basic science discovery all the way through to clinical trials and the development of novel therapies, all within the department and in an expedited fashion. For instance, instead of the standard five- to seven-year industry time frame, the department has moved their attenuated measles virus therapy for ovarian cancer from discovery to clinical trials within three years. This integrated process enables the advancement of science and the quick delivery of new treatments to patients.

Researchers from the Department of Molecular Medicine participate in achieving the center's goal of personalizing each person's treatment for optimal care. The Molecular Medicine department's research team is focused on advancing the center's research into biomarker discovery. Researchers are also actively involved in applying their expertise in gene therapy to the field of regenerative medicine, particularly in the areas of beta cell regeneration and liver regeneration.

The Department of Molecular Medicine works with the Gene and Virus Therapy Program of the Mayo Clinic Cancer Center Research to develop new gene delivery systems and gene and virus-based therapies for cancer treatment. The program conducts research on all Mayo Clinic campuses. The Gene and Virus Therapy Program focuses on four areas of research:

Core facilities such as the Viral Vector Production Laboratory and the Toxicology and Pharmacology Shared Resource manufacture clinical-grade engineered viruses and perform preclinical toxicology and biodistribution studies to support the department's clinical trials.

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Molecular Medicine Research - Department of Molecular ...

NEW YORK (Reuters) - While some potential vaccines have emerged in the global race to find a way to stop the spread of COVID-19, many scientists and researchers believe antibody based therapies hold great promise for treating people already infected with the disease.

FILE PHOTO: An apheresis machine separates and collects convalescent plasma from the whole blood of a recovered coronavirus (COVID-19) patient at the Central Seattle Donor Center of Bloodworks Northwest during the outbreak in Seattle, Washington, U.S. April 17, 2020. The plasma from recovered patients will be used in an experimental treatment study for current coronavirus patients. REUTERS/Lindsey Wasson

These therapies use antibodies generated by infected humans or animals to fight off the disease in patients. They date back to the late 19th century, when researchers used a serum derived from the blood of infected animals to treat diphtheria.

For COVID-19 treatment, researchers are studying the use of convalescent plasma and other treatments made with blood from recently recovered patients.

More recently, scientists have developed treatments called monoclonal antibodies antibodies that can be isolated and manufactured in large quantities to treat diseases like Ebola or cancer. Companies, like Eli Lilly and Co (LLY.N) and Regeneron Pharmaceuticals (REGN.O) in the United States, are trying to use this approach to develop their treatments.

Unlike convalescent plasma, manufacturers do not need a steady supply of antibody-rich blood to produce monoclonal antibodies, so this approach could be easier to scale up.

In general, the goal of a vaccine is to generate an immune response that can prevent someone from getting ill with a disease, whereas antibody-derived products are generally designed to treat disease.

And while some drugmakers have suggested antibody treatments can be used prophylactically - Regenerons Chief Scientific Officer George Yancopoulos has said their treatment could be a bridge to a vaccine - it could be expensive.

You might go into nursing homes or the military and use it because antibodies have a pretty long half life, said Dr. Betty Diamond, Director of Molecular Medicine at the Feinstein Institutes for Medical Research.

You might decide that you are going to use this as a prevention in this very high risk group, but you wouldnt do that for the whole country.

The amount of protein in antibody drugs makes the treatment more expensive than vaccines in general, Feng Hui, chief operating officer at Shanghai Junshi Biosciences (1877.HK), said.

Designing antibody drugs to treat or protect high risk people, including those with weak immune systems, could require hundreds, or even over a thousand times more protein than found in a vaccine shot, according to Junshi.

WHO IS DEVELOPING ANTIBODY THERAPIES FOR COVID-19?

Eli Lilly is collaborating with Junshi and Canadian biotech firm AbCellera Biologics to develop different antibody treatments, both of which have started early stage testing in humans.

Regeneron plans to start clinical studies later this month to test its antibody cocktail treatment, which was derived from antibodies from genetically-modified mice. It aims to have hundreds of thousands of preventative doses available by the end of the summer or the fall.

The CoVIg-19 Plasma Alliance, which includes Japans Takeda Pharmaceuticals (4502.T) and CSL Behring, is working on hyperimmune globulin therapy derived from convalescent plasma, which could offer a standardized dose of antibodies and doesnt need to be limited to patients with matching blood types.

The Antibody Therapy Against Coronavirus (ATAC) project, funded by the European Commission and led by Swedens Karolinska research institute, is looking at a similar approach as well as monoclonal antibodies. Under the project, monoclonal antibodies extracted from convalescent plasma are now being tested on human volunteers in Germany and on animals in Switzerland.

Britains GlaxoSmithKline (GSK.L) is working with Vir Biotechnology Inc (VIR.O) to develop potential antibody treatments which select the best antibodies out of the plasma.

AbbVie (ABBV.N) has also announced a collaboration to develop antibody therapies.

Singapores state research body A*Star is working with Japans Chugai Pharmabody Research on an antibody for clinical use.

Reporting by Michael Erman; Additional reporting by Francesco Guarascio in Brussels, Roxanne Liu in Beijing and John Geddie in Singapore; Editing by Miyoung Kim & Simon Cameron-Moore

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Explainer: What are antibody therapies and who is developing them for COVID-19? - Reuters

Ali Shilatifard

A pandemicespecially one caused by a mysterious or newly discovered infectious agentengenders a stark reminder that supporting fundamental research has been a prudent investment of public funds. Fundamental molecular research plays an essential role in the clinic to decipher infectious processes, develop therapeutic strategies, and guide physicians, nurses, and other hospital employees in implementing the most effective application of new knowledge. As the world begins the process of healing from the medical, social, and economic effects of coronavirus disease 2019 (COVID-19), public health is at the forefront of decision-making by lawmakers at both the federal and state levels. Daily news conferences and press releases illustrate the importance of scientists and physicians as major partners in pandemic task forces, guiding politicians in health policy decision-making. Basic molecular research plays a crucial role in helping the world overcome the current pandemic and prepare for the next one.

The first application of fundamental molecular research to COVID-19 was rapid sequencing of the SARS-CoV-2 RNA genome using a process known as next-generation sequencing (NGS). These data immediately delivered the scientific and clinical communities with insight into the singular properties of this coronavirus strain. NGS can provide billions of DNA reads in a single day, a process that was unfathomable only 15 years ago. Now an essential and nearly ubiquitous technology, NGS evolved through the research of biochemists, molecular biologists, and engineers who were supported by grants from publicly funded institutions such as the U.S. National Institutes of Health (NIH), National Cancer Institute (NCI), and their counterparts across the globe. The second major application of fundamental molecular research to COVID-19 was the development of an assay to identify infected individuals. The method of choice for high-sensitivity detection of the virus in people is reverse transcription followed by polymerase chain reaction (RT-PCR), which takes advantage of the viral genome sequence provided by NGS. A key component of this assay is the reverse transcriptase RNA-dependent DNA polymerase, which converts the viral RNA genome into a DNA molecule that can be amplified and detected. This enzyme was a Nobel prize winning discovery by NIH/NCI-supported researchers Howard Temin and David Baltimore. Although the PCR amplification methods and instruments were finalized in the private sector, much of the enzymology and nucleic acid chemistry that spurred PCR development was based on publicly funded fundamental molecular research.

Developing COVID-19 therapeutics requires an in-depth understanding of molecular processes involved in the viral life cycle. Antiviral therapies are needed to treat patients with mild to moderate symptoms. Additional therapies are needed for COVID-19 patients who suffer cytokine storm, which progresses to critical stages of respiratory failure, septic shock, and multiorgan dysfunction. Given that COVID-19 is within the family of RNA viruses, researchers are well positioned to begin development of antiviral therapies, as biochemists already have generated a plethora of molecular information about the atomic structures for the main enzyme required for viral replication, the RNA-dependent RNA polymerase, an enzyme which has no known host counterpart. In this case, biochemists and transcription biologists have already identified Remdesivir, an adenosine nucleotide analog that interferes with the action of viral RNA-dependent RNA polymerase activity. Clinical trials of the drug are currently underway, and early results are encouraging. As for the treatment of cytokine storm, again, basic biochemical research in immunology has paved the way for the development of several therapies, including interleukin-6 (IL-6) inhibitors that function by blocking the IL-6 receptor and ameliorate unwanted damage to tissues and organs caused by cytokine release as the result of viral infection.

The ultimate aim for the treatment of all viral infections, including COVID-19, is the development of host and herd immunity, which can be accomplished either through host infection or vaccination. To manage potential pandemics with the least number of casualties, researchers must develop vaccines that can be mass produced on a scale of hundreds of millions of doses within in a few months after a virus appears and that can be rapidly distributed across the globe. Traditional vaccines use either active or weakened virus or destroyed forms of viral particles as the immune responsegenerating agent. The use of attenuated and destroyed viral particles as vaccines is highly effective, but the manufacturing process is arduous and time-consuming. Recombinant RNA and DNA vaccines circumvent these shortcomings of traditional vaccine generation and are in clinical trial for COVID-19. In this case, humankind owes biochemists Paul Berg, Walter Gilbert, Frederick Sanger, and their colleagues a debt of gratitude for their Nobel prize winning fundamental research in developing recombinant DNA technologies. This work resulted from decades-long funding by U.S. and U.K. governmental agencies and, today, allows the design of recombinant RNA and DNA vaccines and many other life-saving medicines that take advantage of this revolutionary technology.

Once the dust from the COVID-19 pandemic settles and the U.S. Congress is back in session, I hope that lawmakers will recognize our societys dependence on thorough, methodical, mechanistic science and the medicines it provides and ask themselves how many more people might have perished from COVID-19 without the modern methods that arose from the basic molecular research described above. This catastrophe should be a reminder that a healthy investment in all institutes of the NIH and NCI and other federal science agencies will be life-saving when future pandemics arise.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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Medicine in the time of corona: Fundamental molecular research is essential - Science Advances

Westport, CT, June 08, 2020 (GLOBE NEWSWIRE) --

BioSig Technologies, Inc. (Nasdaq: BSGM) (BioSig or the Company) and its subsidiary, ViralClear Pharmaceuticals, Inc., today announced a reminder that it will host a call to discuss the Phase II clinical trials of merimepodib, its broad-spectrum oral anti-viral candidate for the treatment of COVID-19 in adult patients.

The format will be a management presentation updating recent developments followed by a Q&A session with select call attendees.

Conference Call Details:

Date: Tuesday, June 9, 2020Time: 11:00 AM Eastern Time (ET)Dial in Number for U.S. Callers: 1-877-407-8293Dial in Number for International Callers: 1-201-689-8349

A replay will be available for two weeks starting on June 9, 2020 at approximately 2:00 PM ET. To access the replay, please dial 1-877-660-6853 in the U.S. and 1-201-612-7415 for international callers. The conference ID# is 13704617.

On May 14, 2020, an article titled, "The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro" was published by F1000 Research, an online peer-reviewed life sciences journal publishing program in biology and medicine. The article cites that merimepodib in combination with remdesivir decreases viral production of SARS-CoV-2 to undetectable levels in pre-clinical testing.

On May 18, 2020, ViralClear announced the FDAs clearance of its IND to proceed with a proposed Phase II study of merimepodib in COVID-19 patients. The human clinical trial is planned to be conducted under the leadership of Dr. Andrew D. Badley, Professor and Chair of the Department of Molecular Medicine and the Enterprise Chair of the COVID-19 Task Force at Mayo Clinic.

On June 5, 2020, ViralClear announced that it has expanded its patient enrollment centers to include St. Davids South Austin Medical Center in Austin, TX. The hospital is part of St. Davids HealthCare, one of the largest healthcare systems in Texas. The Company intends to commence its Phase II clinical trial for merimepodib, its broad-spectrum oral anti-viral candidate for the treatment of COVID-19 in adult patients in the coming weeks.

About BioSig Technologies BioSig Technologies is a medical technology company commercializing a proprietary biomedical signal processing platform designed to improve signal fidelity and uncover the full range of ECG and intra-cardiac signals (www.biosig.com).

The Companys first product, PURE EP(tm) System is a computerized system intended for acquiring, digitizing, amplifying, filtering, measuring and calculating, displaying, recording and storing of electrocardiographic and intracardiac signals for patients undergoing electrophysiology (EP) procedures in an EP laboratory.

About Viral Clear Pharmaceuticals and Merimepodib (MMPD)BioSigssubsidiary, ViralClear Pharmaceuticals, Inc., is seeking to develop a novel pharmaceutical called merimepodib to treat patients with COVID-19. Merimepodib is intended to be orally administered, and has demonstrated broad-spectrum in vitro antiviral activity, including strong activity against SARS-CoV-2 in cell cultures. Merimepodib was previously in development as a treatment for chronic hepatitis C and psoriasis by Vertex Pharmaceuticals Incorporated (Vertex), with 12 clinical trials (7 in phase 1 and 5 in phase 2) with over 400 subjects and patients and an extensive preclinical safety package was completed. A manuscript titled, The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro, was submitted to an online peer-reviewed life sciences journal. This manuscript is authored by Natalya Bukreyeva, Rachel A. Sattler, Emily K. Mantlo, John T. Manning, Cheng Huang and Slobodan Paessler of the UTMB Galveston National Laboratory and Dr. Jerome Zeldis of ViralClear Pharmaceuticals, Inc. (ViralClear) as a corresponding author. This article highlights pre-clinical data generated under contract with Galveston National Laboratory at The University of Texas Medical Branch.

Forward-looking StatementsThis press release contains forward-looking statements. Such statements may be preceded by the words intends, may, will, plans, expects, anticipates, projects, predicts, estimates, aims, believes, hopes, potential or similar words. Forward- looking statements are not guarantees of future performance, are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Companys control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the geographic, social and economic impact of COVID-19 on our ability to conduct our business and raise capital in the future when needed, (ii) our inability to manufacture our products and product candidates on a commercial scale on our own, or in collaboration with third parties; (iii) difficulties in obtaining financing on commercially reasonable terms; (iv) changes in the size and nature of our competition; (v) loss of one or more key executives or scientists; and (vi) difficulties in securing regulatory approval to market our products and product candidates. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Companys filings with the Securities and Exchange Commission (SEC), including the Companys Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Investors and security holders are urged to read these documents free of charge on the SECs website at http://www.sec.gov. The Company assumes no obligation to publicly update or revise its forward-looking statements as a result of new information, future events or otherwise.

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Reminder - BioSig Subsidiary, ViralClear to Host Conference Call on June 9th to Discuss Upcoming and Recent Developments for Phase II Human Clinical...

An international team of investigators has recently discovered that the receptor tyrosine-kinase EphA2 activated by the growth factor progranulin is a tumorigenic driver of bladder cancer progression.

The study, Progranulin/EphA2 axis: A novel oncogenic mechanism in bladder cancer, has been recently published in the international-peer-reviewed journal Matrix Biology. The paper describes how EphA2 depletion severely blunted progranulin-dependent motility and anchorage-independent growth, and sensitized bladder cancer cells to cisplatin treatment.

The authors, including Dr. Andrea Morrione, currently at the Sbarro Institute for Cancer Research and Molecular Medicine, and the Center for Biotechnology at Temple University, Dr. Renato V. Iozzo from the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, and Dr. Antonino Belfiore from the University of Catania, Italy, had previously demonstrated that the growth factor progranulin plays a critical role in bladder cancer by modulating tumor cell motility and invasion, and discovered that progranulin targeting markedly reduces in vivo tumor growth and sensitizes urothelial cancer cells to cisplatin treatment. The authors recently identified EphA2, a member of a large family of receptor tyrosine-kinases, as the functional receptor for progranulin. However, It was not previously established whether EphA2 plays an oncogenic role in bladder cancer.

This study demonstrates that progranulin is the predominant EphA2 ligand in bladder cancer. Progranulin evokes Akt- and Erk1/2-mediated EphA2 phosphorylation at Ser897, which could drive bladder tumorigenesis. They further defined the mechanisms of progranulin/EphA2-dependent motility by identifying liprin-1 as a novel progranulin-dependent EphA2 interacting protein and establishing its critical role in cell motility.

As stated by Dr. Antonio Giordano, Founder and Director of the Sbarro Health Research Organization at Temple University, the discovery of EphA2 as the functional signaling receptor for progranulin and the identification of novel downstream effectors offers a new avenue for understanding the underlying mechanism of progranulin action, and may constitute novel clinical and therapeutic targets in bladder cancer.

Bladder cancer is one of the most common and aggressive cancers worldwide and, regardless of the treatment, often recurs and spreads to surrounding tissues. Thus, a deeper knowledge of the mechanisms driving bladder tumorigenesis is critical for novel rational therapeutic strategies.

About the Sbarro Health Research OrganizationThe Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visitwww.shro.org

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Targeting Receptor EphA2 Reduces Bladder Cancer Tumor Growth and Increases Chemotherapy Effectiveness - Newswise

The paper also suggests the likeliness of the gut microbiota being disrupted in severe COVID-19 patients, which may affect disease outcomes, including predisposition to secondary bacterial infections of the lung.

Jose Bengoechea, Professor of Molecular Microbiology and Director of Wellcome Wolfson Institute for Experimental Medicine at Queen's University, explains: "The lack of therapies to treat severe COVID-19 patients led clinicians to use a number of treatments to modify the activity of their immune system.

"However, it is important to note that these interventions may also increase the risk of potentially fatal secondary bacterial respiratory infections.

"Therefore, careful consideration should be given whether any potential new therapy may affect the patients' defences against bacterial infections. We believe that there is an urgent need to develop new therapeutics to treat COVID-19 targeting the virus/bacteria co-infection scenario."

The research also raises concerns about the impact of COVID-19 on antimicrobial resistance (AMR) globally.

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COVID-19: Researchers warn of sharp rise in antimicrobial resistance - National Herald

Estonian scientists are developing a DNA-based method of analysis that enables them to identify food components and specify the origin of a foodstuff.

Bioinformatics specialists at the University of Tartu, in cooperation with the Competence Centre on Health Technologies, have published a research paper in the journal Frontiers in Plant Science in which they indicated the possibility to identify components in thermally processed food using DNA analysis even if the quantities were very small. The scientists analysed thermally processed cookies that contained a small amount of lupin flour. The DNA analysis provided reliable identification of lupin even when the lupin flour content in the dough was just 0.02%.

Food always contains the DNA traces of the plants, animals and microorganisms that have been used or that the food or its raw materials have come into contact with in the production process. DNA analysis can provide valuable information on the content, origin, safety and health benefits of food and will make the identification of counterfeit foods and non-compliances in the ingredients specified on the packaging more reliable in the future. For example, certain cases gained attention last year in which the origin of honey and the authenticity of Estonian honey needed verification. The novel DNA analysis would make it possible to solve such issues.

According to Kairi Raime, the lead author of the article, Research Fellow of Bioinformatics at the Institute of Molecular and Cell Biology and a doctoral student at the University of Tartu, their method is a major step forward in the development of DNA-based methods for food analysis. "Our method helps to identify the actual biological contents and origins of food via DNA information and thus ensures the safety and authenticity of the food," she explained. Raime is planning to defend her PhD dissertation on the topic.

The DNA may be significantly degraded in processed food. Scientists extracted DNA from the cookies and analysed it using DNA sequencing technology. For the analysis of a single biscuit, approximately 20 million DNA sequences were obtained. Based on these, and by using bioinformatic analysis, it was possible to specify the DNA of the species found in the sample analysed. The main issue was the preparation of the DNA for sequencing, as the DNA is often degraded in food and even minute amounts of DNA molecules must be identified.

Kaarel Krjutkov, Head of the Precision Medicine Laboratory of the Competence Centre on Health Technologies and Senior Research Fellow of Molecular Medicine at the University of Tartu, whose laboratory was used to prepare the sequencing of the DNA extracted from the biscuits, noted that faking the DNA fingerprint of a food is complicated and expensive, and it is therefore cheaper to offer authentic food. "People can see that in medicine, precise DNA analysis is already a reality, but in food industry and in the field of food safety, the golden age of DNA-based analysis is yet to come," Krjutkov remarked.

The research used a method based on short, unique DNA sequences (k-mers) for analysing genomic DNA data, which enables the scientists to quickly identify plant or bacterial DNA present in a food or an environmental sample. The Chair of Bioinformatics at the Institute of Molecular and Cell Biology at the University of Tartu has been developing competence in the bioinformatics of k-mers and DNA analysis over the last five years. The software developed in the Chair of Bioinformatics has been used both in medicine and for providing food safety.

The article authors' earlier cooperation resulted in the NIPTIFY foetal chromosomal disorder test, which helps to detect, with almost 100% accuracy, the DNA sequences causing foetal Down syndrome in the mother's blood sample as early as the tenth week of pregnancy. The genome analysis method developed in the Chair of Bioinformatics is used to identify pathogenic bacteria, specify their disease-causing capabilities and predict antibiotic resistance. This enabled Maido Remm, Professor of Bioinformatics at the University of Tartu, and his working group to advise the management board of a production company contaminated with a dangerous strain and to help determine the spread of type ST1247 in the company during the listeria outbreak in autumn 2019.

According to Remm, the research article proves that DNA sequencing can also be used for identifying allergenic ingredients in processed food. "DNA sequencing is a promising diagnostic method which makes it possible to quickly obtain precise information about food and the microbes around us," he said. "The use of sequencing and k-mers makes it possible in a very short time to implement a diverse range of diagnostic tests that meet the needs of researchers and companies."

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Novel DNA analysis will help to identify food origin and counterfeit food in the future - Science Codex

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COVID-19 has jolted the global discourse on public health into a rapid redo. To be or not to be is no longer a question or topic of debate for digital health. Embracing digital technology and data science for global health is the only way to reverse the pandemic in the short-term, and to make health systems combat-ready for the future ones.

Whether at the national or the global level, the game plan of each country will necessarily include technology-enabled defence and offence strategies to strengthen health systems. The paradigm of preparedness against future health threats will transform digital health; simultaneously, it shall also change the professional profile, skillset and toolbox of frontline health soldiers.

As governments across the world invest in expanding digital and mobile connectivity for integrating technology with health systems, an equally pressing question needs concurrent intervention. Is todays healthcare workforce prepared to deliver a digital future? The answer is a straight no on both dimensions of service preparedness, i.e., capacity and capability.

On global capacity, the total demand for health workers has always outpaced supply, with shortages varying between manageable to stark levels based on a countrys socio-economic status. With COVID-19 proving to be a brutal blow to the best-prepared health systems, health workforce capacity building has become a priority world over. An estimate by the World Health Organisation projects the global aggregate demand for 80.2 million health workers across 165 countries by 2030, whereas the current number is around 48 million.

Trained healthcare personnel, however, cannot be increased in a matter of months. It is a long-drawn process, which must begin soon enough to cover the shortage of millions of health workers. With economies slipping in a downward spiral, there is an added impetus to act quickly. It is well-established that investing in the health sector accelerates employment generation, especially for women and youth. There lies an opportunity to build the capability set of new entrants in health services based on future needs of health eco-systems. In years to come, the delivery and consumption of health will be more technology-driven than ever before. The profile of health workforce of each country must be aligned with the digital health priorities it sets for itself. While the exact construct will differ by country, the broad direction will be a combination of the principles outlined below.

For todays health workers, digitalisation of health systems and implementation of the connected care blueprint in a localised manner will shape new ways of doing their jobs. It will be in a hybrid format, comprising physical and digital care of patients in varied proportions to maximise health outcomes.

Technology integration within clinical services and products will also create new types of jobs to invent and handle public goods or medical products of future (new-age therapeutics, diagnostics and preventive health aides) using a combination of biology and computer science. They will fall at the intersection of medicine, genomics and engineering, using Artificial Intelligence (AI), Machine learning (ML), robotics, predictive analytics, and more.

It calls for urgent and parallel action by governments to kick-off upskilling and mindset rewiring of professionals in the medical and biopharma domains to adopt digital tools in their practice. The recent use case of telemedicine to deliver virtual care (force-started by COVID-19) is a glimpse into the future of model patient and physician behaviour on technology adoption. Yet, it is not fully reflective of the scale at which evolving trends in healthtech will define the speed and nature of skillset transformation for health workers in primary and tertiary care settings.

To drive the upskilling exercise, it is also critical to gauge the aptitude and willingness of todays health workers to use technology in clinical decision-making.

Pre-covid times have seen stinging debates within the medical community and health policymakers on whether technology will strip healthcare off its essential nature of being high-touch for effective patient care. Questions have been raised if AI tools will depersonalise medicine; if standard of care will dilute, or patient-centricity will be lost if AI/ML algorithms were to read radiology scans and vital signs to present clinical diagnosis or to predict disease prognosis. Legitimate doubts and ethical concerns on patients rights and data privacy have been brought forward. Most importantly, fair scepticism has been raised on safety and trustworthiness of algorithms due to inherent socio-ethnic biases and lack of situational context.

As a result, the digital health discourse has so far seen three types of participants: the Evangelists, who strongly believe that healthtech will catapult countries to meet sustainable development goals; the Cynics, who have raised many of the above questions; and the Opposers, who view technology as a threat to their careers or as an unwanted intrusion in the age-old, sacred practice of medicine.

Post covid, the narrative has stepped up considerably to gain the attention of the healthcare community around the world. The goings-on have led many Cynics and Opposers to shift their position into the solution-seeking quadrant, to coalesce into a new category of Constructive Critics. Together, the Evangelists and the Constructive Critics will form a powerful community to extract the most-balanced and effective benefits of digital and AI/ML technology in healthcare delivery, without diluting patient-centricity, data security and privacy rights. They will also be the change catalysts, who will lay down the foundation and constructs of the new system to work as inter-disciplinary teams, and to train and arm the workforce of today with digital skills.

As a long-term goal, cultivating aptitude and imparting new skills to create a digital-savvy health workforce of the future calls for considerable reform in the medical education system. This will need a redesign of curricula, training methods and skill evaluation techniques. In addition, student selection criteria and aptitude tests for clinical careers will have to be revamped.

Institutional frameworks of medical and nursing schools will have to create flexible claw-ins with technical education institutes to co-develop matrixed pedagogy programmes. For example, a medical science, nursing, or paramedical student would necessarily have to take credit courses in computer science, bio-engineering, mathematics or allied disciplines. Similarly, it will be essential for engineering and mathematics students to partake selective medical courses, to gain insights and orientation on experiences and challenges of patients and health workers in clinical settings to conceive future digital products for the healthcare and life sciences sectors. Selection and training for primary health workers will also incorporate digital literacy as an essential requirement.

Few countries such as the UK and Australia had begun deliberation on their workforce strategy to enable digital health last year. For example, in 2019, the National Health Service, UK identified genomics, telemedicine and AI-based technologies as thrust areas to plan training and education of their future workforce.

To sum-up, the future will have inter-professional teams working in collaboration to co-create and monitor learning systems behind clinical decision making digital tools. Frontrunners for these roles will be the ones with a combination skillset in technology and clinical sciences or techlinical. All health workers will be digital-savvy to deploy these tools in care settings to improve patient outcomes. The combined effect of both will increase efficiency and effectiveness of delivery at a systemic level. As predicted by digital health evangelist, Dr.Eric Topol (Professor of Molecular Medicine, Scripps Research Translational Institute), use of AI and technology-aides in medicine will create time and space to deliver real healing to the patients.

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Health Workforce of the Digital Future: Techlinical Cross-products - Observer Research Foundation

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Chemical compound restores tetracycline's effectiveness by blocking bacterial resistance

Shown above are two different 3D views of TetX7 (green), a tetracycline-destroying enzyme that causes resistance to all tetracycline antibiotics (the small multicolored molecule in the center). Researchers at Washington University in St. Louis and the National Institutes of Health (NIH) have found that genes that confer the power to destroy tetracyclines are widespread in bacteria that live in the soil and on people.

The latest generation of tetracyclines a class of powerful, first-line antibiotics was designed to thwart the two most common ways bacteria resist such drugs. But a new study from researchers at Washington University in St. Louis and the National Institutes of Health (NIH) has found that genes representing yet another method of resistance are widespread in bacteria that live in the soil and on people. Some of these genes confer the power to destroy all tetracyclines, including the latest generation of these antibiotics.

However, the researchers have created a chemical compound that shields tetracyclines from destruction. When the chemical compound was given in combination with tetracyclines as part of the new study, the antibiotics lethal effects were restored.

The findings, available online in Communications Biology, indicate an emerging threat to one of the most widely used classes of antibiotics but also a promising way to protect against that threat.

We first found tetracycline-destroying genes five years ago in harmless environmental bacteria, and we said at the time that there was a risk the genes could get into bacteria that cause disease, leading to infections that would be very difficult to treat, said co-senior author Gautam Dantas, PhD, a professor of pathology and immunology and of molecular microbiology at Washington University School of Medicine in St. Louis. Once we started looking for these genes in clinical samples, we found them immediately. The fact that we were able to find them so rapidly tells me that these genes are more widespread than we thought. Its no longer a theoretical risk that this will be a problem in the clinic. Its already a problem.

In 2015, Dantas, also a professor of biomedical engineering, and Timothy Wencewicz, PhD, an associate professor of chemistry in Arts & Sciences at Washington University, discovered 10 different genes that each gave bacteria the ability to dice up the toxic part of the tetracycline molecule, thereby inactivating the drug. These genes code for proteins the researchers dubbed tetracycline destructases.

But they didnt know how widespread such genes were. To find out, Dantas and first author Andrew Gasparrini, PhD then a graduate student in Dantas lab screened 53 soil, 176 human stool, two animal feces, and 13 latrine samples for genes similar to the 10 theyd already found. The survey yielded 69 additional possible tetracycline-destructase genes.

Then they cloned some of the genes into E. coli bacteria that had no resistance to tetracyclines and tested whether the genetically modified bacteria survived exposure to the drugs. E. coli that had received supposed destructase genes from soil bacteria inactivated some of the tetracyclines. E. coli that had received genes from bacteria associated with people destroyed all 11 tetracyclines.

The scary thing is that one of the tetracycline destructases we found in human-associated bacteria Tet(X7) may have evolved from an ancestral destructase in soil bacteria, but it has a broader range and enhanced efficiency, said Wencewicz, who is a co-senior author on the new study. Usually theres a trade-off between how broad an enzyme is and how efficient it is. But Tet(X7) manages to be broad and efficient, and thats a potentially deadly combination.

In the first screen, the researchers had found tetracycline-destructase genes only in bacteria not known to cause disease in people. To find out whether disease-causing species also carried such genes, the scientists scanned the genetic sequences of clinical samples Dantas had collected over the years. They found Tet(X7) in a bacterium that had caused a lung infection and sent a man to intensive care in Pakistan in 2016.

Tetracyclines have been around since the 1940s. They are one of the most widely used classes of antibiotics, used for diseases ranging from pneumonia, to skin or urinary tract infections, to stomach ulcers, as well as in agriculture and aquaculture. In recent decades, mounting antibiotic resistance has driven pharmaceutical companies to spend hundreds of millions of dollars developing a new generation of tetracyclines that is impervious to the two most common resistance strategies: expelling drugs from the bacterial cell before they can do harm, and fortifying vulnerable parts of the bacterial cell.

The emergence of a third method of antibiotic resistance in disease-causing bacteria could be disastrous for public health. To better understand how Tet(X7) works, co-senior author Niraj Tolia, PhD, a senior investigator at the National Institute of Allergy and Infectious Diseases at the NIH, and co-author Hirdesh Kumar, PhD, a postdoctoral researcher in Tolias lab, solved the structure of the protein.

I established that Tet(X7) is very similar to known structures but way more active, and we dont really know why because the part that interacts with the tetracycline rings is the same, Kumar said. Im now taking a molecular dynamics approach so we can see the protein in action. If we can understand why it is so efficient, we can design even better inhibitors.

Wencewicz and colleagues previously designed a chemical compound that preserves the potency of tetracyclines by preventing destructases from chewing up the antibiotics. In the most recent study, co-author Jana L. Markley, PhD, a postdoctoral researcher in Wencewiczs lab, evaluated that inhibitor against the bacterium from the patient in Pakistan and its powerful Tet(X7) destructase. Adding the compound made the bacteria two to four times more sensitive to all three of the latest generation of tetracyclines.

Our team has a motto extending the wise words of Benjamin Franklin: In this world nothing can be said to be certain, except death, taxes and antibiotic resistance, Wencewicz said. Antibiotic resistance is going to happen. We need to get ahead of it and design inhibitors now to protect our antibiotics, because if we wait until it becomes a crisis, its too late.

Gasparrini AJ, Markley JL, Kumar H, Wang B, Fang L, Irum S, Symister C, Wallace M, Burnham CAD, Andleeb S, Tolia NH, Wencewicz TA, Dantas G. Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance. Communications Biology. May 15, 2020. DOI: 10.1038/s42003-020-0966-5

This work is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH), grant number R01 AI123394; the National Institute of General Medical Sciences, training grant number T32 GM007067; the National Institute of Diabetes and Digestive and Kidney Diseases, training grant number T32 DK077653; and Washington University, W.M. Keck Postdoctoral Program in Molecular Medicine and the Chancellors Graduate Fellowship Program.

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

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Antibiotic-destroying genes widespread in bacteria in soil and on people - Washington University School of Medicine in St. Louis

If you have irritable bowel syndrome (IBS), the foods you eat can make all the difference in how you feel. Some foods can trigger symptoms, and limiting them may mean less abdominal pain, bloating, gas and constipation.

Symptom triggers are different for everyone, but cheese and pasta may be some of the foods to avoid with IBS.

Image Credit: vadimguzhva/iStock/GettyImages

Find out which foods may be aggravating your IBS and what you can choose instead, so you can enjoy your meals with less stress.

Cow's milk and other dairy products containing lactose like yogurt, ice cream, cream cheese and cottage cheese can trigger IBS symptoms.

Lactose is a sugar that's tough to digest, according to Harvard Health Publishing, as well as a FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols). FODMAPs are short-chain carbohydrates that can cause gastrointestinal distress.

What to eat instead: Try pouring lactose-free, oat, almond or rice milk into your cereal or coffee. You can also try dairy-free yogurts and ice creams. Hard cheeses are also a better choice than soft cheeses as they contain less lactose, according to the Cleveland Clinic.

Not being able to enjoy a cup or two of coffee or tea in the morning is a tough reality for some IBS sufferers, but caffeine is a stomach irritant that can increase diarrhea, according to John Hopkins Medicine. But don't despair, sleepyheads! According to an article published June 2017 in the World Journal of Gastroenterology, caffeine may be tolerated if it's restricted to 400 milligrams.

What to drink instead: If it's still a big no for you, there are many good substitutions. "Herbal teas, things like Teeccino and Dandy Blend tea are also great they're kind of like coffee but aren't," says Isabel Smith, RD, CDN. "There are mushroom elixirs (like Four Sigmatic), and a good cup of ginger in hot water can also do the trick for energy and soothing."

3. Foods High in Fructose

Being cautious with certain fruits, drinks and processed foods containing high amounts of fructose, a FODMAP compound, can help with IBS symptoms. According to Food Intolerance Diagnostics, it's a good idea to limit the following:

Processed foods containing high-fructose corn syrup, honey, agave nectar or molasses should also be limited or avoided.

What to eat instead: Reach for cantaloupe, grapes, kiwi, oranges, pineapple, strawberries, eggplant, green beans, bok choy, carrots, cucumber, lettuce, potatoes, spinach and zucchini, which are gentler on the digestive system. Also, you should start becoming a staunch label sleuth with those processed foods!

Vegetables like cabbage, cauliflower, Brussels sprouts and broccoli are rich in vitamins and minerals and full of cancer-fighting phytonutrients. But they're also high in fructans and galactooligosaccharides, says gastroenterologist Jacqueline Wolf, MD.

"These are inadequately broken down by digestion and give gas and bloating," Dr. Wolf says.

What to eat instead: If these foods trigger symptoms for you, you can still get your fill with easier-to-digest veggies like eggplant, green beans, bok choy, carrots, cucumbers, lettuce, potatoes, spinach and zucchini. And eat up, becausenutrients!

Beans, chickpeas, lentils and soy beans are protein powerhouses and excellent sources of minerals like iron, magnesium and zinc. But they're all high in fiber and contain oligosaccharides (a FODMAP compound), according to the U.S. Dry Beans Council, which means they may cause some major bloating and gas issues.

What to eat instead: There aren't any real "replacements" for beans, but you can try soaking them in water overnight to tame gas-producing substances, according to the Cleveland Clinic. And keep in mind that you may react differently to different types of legumes, so you may want to test out your reaction before you write them out of your diet completely.

6. Sugar Alcohols (Polyols)

You may be tempted to reach for sugar-free foods if you're watching your weight, but many of these foods contain sugar alcohols (substitutes) like the polyols: sorbitol, xylitol, lactitol, mannitol, erythritol and maltitol. These FODMAPs, according to a September 2016 article in the International Journal of Dentistry, may cause gas, bloating and diarrhea, so it's probably best to limit sugarless gum and any other food labeled "sugar-free."

What to eat instead: "Eat food with real sugar in it! I can't say this enough it makes a huge difference for people, especially with IBS," Smith tells LIVESTRONG.com.

This type of fiber (roughage), promotes the movement of material through your digestive system and increases stool bulk, as it isn't broken down by the gut, according to the Mayo Clinic. This is good news for most people, but a June 2017 article in the International Journal of Molecular Medicine noted that insoluble fiber may cause diarrhea in IBS sufferers.

What to eat instead: You may want to try some foods containing soluble fiber, which may slow things down a bit. Citrus fruits, carrots and barley are good choices.

Having a glass of wine or a cocktail here and there may be OK for some, but consuming a lot of alcohol (binge drinking) can wreak havoc on your digestive system. Alcohol acts as an irritant and increases digestive juices, slowing down the digestive process, according to an article published in 2017 in Alcohol Research: Current Reviews. And findings in a study published in February 2013 in the American Journal of Gastroenterology showed that heavy alcohol intake may exacerbate gastrointestinal symptoms with IBS.

Also, pay attention to what you're ordering, Jenny Champion, RD, CPT, suggests, because it may not be the alcohol that's causing the issue. Barley in beer or the sugary or carbonated drinks mixed with the alcohol may trigger symptoms.

What to drink instead: Wine and martinis mixed with natural ingredients like mint, basil and ginger are safer options, Champion says. And remember to practice moderation.

Gluten is a protein found in many carbohydrate foods like bread, pasta, bagels and some cereals. Because they contain fructans and are high on the FODMAP list, these foods can aggravate your stomach. Granted, you could just have a gluten sensitivity, but you should definitely be checked for Celiac Disease if gluten does do a number on you.

What to eat instead: Unless you have another serious GI issue, such as celiac disease, it's not a good idea to eliminate gluten altogether, according to The Ohio State University Wexner Medical Center, since these foods provide important nutrients. Rather, try avoiding these foods for a couple weeks, then slowly reintroducing them to determine your level of intolerance.

If you do have to avoid gluten, though, there are many gluten-free options available in your grocery store and at most restaurants.

Soda, seltzer and club soda are often big contributors to IBS symptoms, particularly a bloated belly. The fizz can bubble up in your digestive tract, causing belching, bloating and gas, per the American College of Gastroenterology. And you're also hit with a double-whammy since many of these drinks have artificial sweeteners.

What to drink instead: There are plenty of ways to hydrate without the bubbles. Smith suggests tea, fruit-infused water and fresh veggie/fruit juices (that are FODMAP-compliant, of course.). Freezing bits of fruit and herbs or spices in ice cube trays to drop into a tall glass of H2O is another fun idea.

Need a way to easily track your daily water intake? Download the MyPlate app to do the job, so you can stay focused and achieve your goals!

It's hard not to indulge sometimes, but for IBS sufferers, chocolate may be a big no-no. Chocolate contains caffeine approximately 6 milligrams per ounce in milk chocolate and 23 in dark. But dark may be the safer bet, as it shouldn't contain any lactose. Unfortunately, there can be traces of milk in dark chocolate, according to the U.S. Food and Drug Administration.

What to eat instead: Those who can't have any lactose should check the advisory statement on dark chocolate packaging (like "may contain dairy" or "made on equipment shared with milk").

There are dairy-free and vegan chocolate options, but again, check the packaging and labels to make sure they don't contain any triggering ingredients.

Link:

11 Foods to Avoid With IBS - LIVESTRONG.COM

Stem cell researchers at Lund University in Sweden have developed a new research model of the early embryonic brain. The aim of the model is to study the very earliest stages of brain to understand how different regions in the brain are formed during embryonic development. With this new insight, researchers hope to be able to produce different types of neural cells for the treatment of neurological diseases more efficiently. The study is published in the journal Nature Biotechnology.

In order to develop stem cell treatments for neurological diseases such as Parkinson's Disease, epilepsy and stroke, researchers must first understand how the human brain develops in the embryonic stage. With knowledge of how neural cells are formed at different developmental stages, researchers have the opportunity to develop new stem cell therapies more quickly in the laboratory.

"The challenge is that there are thousands of different sub-types of neural cells in the human brain, and for each disease we need to be able to produce exactly the right type of neural cell", says Agnete Kirkeby, researcher at the Wallenberg Centre for Molecular Medicine and the Department of Experimental Medical Science at Lund University.

Studies on how each individual neural cell forms in the embryo during brain development are essential for the researchers to be able to understand how to produce these specific cells in the laboratory.

Research on the early development of the human brain, from five days after the fertilisation of the cell to approximately seven weeks, have so far been difficult as researchers have not had access to human embryonic tissue from these early stages of development. Therefore, nearly all knowledge of the earliest development of the brain is based on studies in flies, chickens and mice.

"However, the composition of the human brain differs greatly from the animals' brains. Therefore, this period in the development of the human brain has long been viewed as the black box of neurology", says Agnete Kirkeby.

Together with colleagues from the University of Copenhagen and bioengineers Thomas Laurell and Marc Isaksson from the Faculty of Engineering at Lund University, Agnete and her team have now created a model that mimics the early developmentalstages of the human brain through the use of stem cells. The stem cells are cultivated in a custom-built cell culture chamber where they are exposed to an environment which resembles the environment in the early embryonic brain.

"In the laboratory model called MiSTR (Microfluidic-controlled Stem cell Regionalisation), we can create tissue that contains different brain regions next to each other, similar to an embryonic brain approximately four to five weeks after fertilisation."

"We start with a small group of cells that will form the brain and instruct the cells by exposing them to a gradient of a specific growth factor (WNT) so that they form different regions of the brain. Our model is better than previously published models because it is much more reproducible and contains more brain regions. We can now use it to study unknown characteristics in the early development of the human brain", explains Agnete Kirkeby.

Agnete Kirkeby believes that the new method may be used to investigate how brain cells in the early embryonic stages react to certain chemicals surrounding us in our daily lives

"This is a significant step forward for stem cell research. For the first time, we now have access to tissue that resembles the early embryonic brain and can therefore study processes behind brain development in a way that has not been possible before. We can for instance use it for testing how chemical substances in our environment might impact on embryonic brain development." explains Kirkeby.

Another aim for the future is to use the model to create a complete map of the development of the human brain. This will help to speed up the development of new stem cell treatments for neurological diseases.

"Once we have the map we will also become better at producing human neural cells in the laboratory that could be used for transplantations, regenerative therapy and to study the brain's function as well as different disease states. . It took us ten years to develop a stem cell treatment for Parkinson's disease because our methods were dependent on trial and error. Our goal is that this process will be much faster in the future for other diseases", concludes Agnete Kirkeby.

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New method provides unique insight into the development of the human brain - Science Codex

ROCKVILLE, Md., May 26, 2020 (GLOBE NEWSWIRE) -- Cerecor Inc. (NASDAQ: CERC) and Myriad Genetics Inc. (NASDAQ: MYGN) today announced that levels of novel cytokine, LIGHT, were highly correlated with disease severity and mortality in a COVID-19 acute respiratory distress syndrome (ARDS) biomarker study. The biomarker study was conducted using the serum samples of 47 hospitalized COVID-19 patients and 30 healthy controls from Hackensack Meridian Health Network.

In April 2020, approximately 1,500 people in the United States died each day from COVID-19. The viral infection triggers a hyperactive immune response leading to cytokine storm and Acute Respiratory Distress Syndrome (ARDS), which is a leading cause of death in patients who die of COVID-19. Although this hyperinflammatory process is poorly understood, the data from this study implicates the inflammatory cytokine, LIGHT, as a potential key driver of cytokine storm leading to ARDS and death.

LIGHT levels were significantly elevated in the serum of hospitalized patients with COVID-19 versus healthy controls (p value < 0.0001). The highest LIGHT levels were found in patients who required ventilator support, particularly in patients over 60. Importantly, the data demonstrated elevated LIGHT levels were also strongly linked with mortality (p=0.02).

Dr. David Perlin, Ph.D., chief scientific officer, senior vice president of the Center for Discovery and Innovation, and Professor of Medical Sciences at the Hackensack Meridian School of Medicine at Seton Hall University, commented These data are compelling and demonstrate that the inflammatory cytokine LIGHT may play a key role in cytokine storm associated with COVID-19 ARDS that leads to increased morbidity and mortality. Reducing LIGHT levels might be a key to dampening the cytokine storm in these patients, preventing the need for ventilator support and reducing mortality.

Dr. Garry Neil, M.D. chief scientific officer, Cerecor commented, As a company, we recognized the impact of cytokine storm-induced ARDS and the need for treatment options for patients in this area of high unmet need. We remain focused on the CERC-002 clinical program and rapidly moving it forward for the treatment of cytokine storm induced ARDS.

Role of LIGHT in Acute Inflammatory Response

LIGHT (homologous to Lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is a cytokine with inflammatory actions encoded by the TNFSF14 gene. LIGHT has been shown to play a key role in the immune response to viral pneumonia. LIGHT plays an important role in regulating immune responses in the lung, gut and skin. It stimulates T Cell and B Cell response as well as induces the release of other cytokines such as IL1, IL6, IL-8, IL-10, TNF and GM-CSF.

CERC-002 (anti-LIGHT monoclonal antibody)

CERC-002 is a fully human monoclonal antibody with neutralizing action against LIGHT (TNFSF14), for treatment of children with Pediatric Crohns Disease. Cerecor holds an open IND with FDA and the drug is currently being studied in a Phase I clinical trial for patients with refractory severe Crohns disease, currently not recruiting due to COVID-19.

Free LIGHT Assay from Myriad RBM

Myriad RBM, a subsidiary of Myriad Genetics, Inc., in collaboration with Cerecor has developed an ultrasensitive assay for the detection of free LIGHT. The assay is validated for serum or plasma samples and has sufficient sensitivity to reliably measure LIGHT from normal and disease subjects.

About Myriad

Myriad Genetics Inc., is a leading personalized medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on three strategic imperatives: transitioning and expanding its hereditary cancer testing markets, diversifying its product portfolio through the introduction of new products and increasing the revenue contribution from international markets. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

About Hackensack Meridian Health

Hackensack Meridian Health is a leading not-for-profit health care organization that is the largest, most comprehensive and truly integrated health care network in New Jersey, offering a complete range of medical services, innovative research and life-enhancing care. Hackensack Meridian Health comprises 17 hospitals from Bergen to Ocean counties, which includes three academic medical centers Hackensack University Medical Center in Hackensack, Jersey Shore University Medical Center in Neptune, JFK Medical Center in Edison; two children's hospitals - Joseph M. Sanzari Children's Hospital in Hackensack, K. Hovnanian Children's Hospital in Neptune; nine community hospitals Bayshore Medical Center in Holmdel, Mountainside Medical Center in Montclair, Ocean Medical Center in Brick, Palisades Medical Center in North Bergen, Pascack Valley Medical Center in Westwood, Raritan Bay Medical Center in Old Bridge, Raritan Bay Medical Center in Perth Amboy, Riverview Medical Center in Red Bank, and Southern Ocean Medical Center in Manahawkin; a behavioral health hospital Carrier Clinic in Belle Mead; and two rehabilitation hospitals JFK Johnson Rehabilitation Institute in Edison and Shore Rehabilitation Institute in Brick. Additionally, the network has more than 500 patient care locations throughout the state which include ambulatory care centers, surgery centers, home health services, long-term care and assisted living communities, ambulance services, lifesaving air medical transportation, fitness and wellness centers, rehabilitation centers, urgent care centers and physician practice locations. Hackensack Meridian Health has more than 34,100 team members, and 6,500 physicians and is a distinguished leader in health care philanthropy, committed to the health and well-being of the communities it serves.

About the Center for Discovery and Innovation

The Center for Discovery and Innovation (CDI), a newly established member of Hackensack Meridian Health, seeks to translate current innovations in science to improve clinical outcomes for patients with cancer, infectious diseases and other life-threatening and disabling conditions. The CDI, housed in a fully renovated state-of-the-art facility, offers world-class researchers a support infrastructure and culture of discovery that promotes science innovation and rapid translation to the clinic.

About Cerecor

Cerecor is a biopharmaceutical company focused on becoming a leader in development and commercialization of treatments for rare pediatric and orphan diseases. The Company is advancing an emerging clinical-stage pipeline of innovative therapies. The Companys pediatric rare disease pipeline is led by CERC-801, CERC-802 and CERC-803 (CERC-800 programs), which are therapies for inborn errors of metabolism, specifically disorders known as Congenital Disorders of Glycosylation (CDGs). The FDA granted Rare Pediatric Disease Designation and Orphan Drug Designation (ODD) to all three CERC-800 programs, thus potentially qualifying the Company to receive a Priority Review Voucher (PRV) upon approval of a new drug application (NDA). The Company is also developing CERC-002, CERC-006 and CERC-007. CERC-007 is an anti-IL-18 monoclonal antibody being developed for the treatment of autoimmune inflammatory diseases such as Adult Onset Stills Disease (AOSD) and Multiple Myeloma (MM). CERC-006 is a dual mTOR inhibitor being developed for the treatment of complex Lymphatic Malformations. CERC-002 is an anti-LIGHT monoclonal antibody being developed for the treatment of Pediatric-onset Crohns Disease.

For more information about Cerecor, please visit http://www.cerecor.com.

Forward-Looking Statements

This press release may include forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. Such forward-looking statements are subject to significant risks and uncertainties that are subject to change based on various factors (many of which are beyond Cerecors control), which could cause actual results to differ from the forward-looking statements. Such statements may include, without limitation, statements with respect to Cerecors plans, objectives, projections, expectations and intentions and other statements identified by words such as projects, may, might, will, could, would, should, continue, seeks, aims, predicts, believes, expects, anticipates, estimates, intends, plans, potential, or similar expressions (including their use in the negative), or by discussions of future matters such as: the development of product candidates or products; timing and success of trial results and regulatory review; potential attributes and benefits of product candidates; and other statements that are not historical. These statements are based upon the current beliefs and expectations of Cerecors management but are subject to significant risks and uncertainties, including: drug development costs, timing and other risks, including reliance on investigators and enrollment of patients in clinical trials, which might be slowed by the COVID-19 pandemic; regulatory risks; Cerecor's cash position and the need for it to raise additional capital; general economic and market risks and uncertainties, including those caused by the COVID-19 pandemic; and those other risks detailed in Cerecors filings with the Securities and Exchange Commission. Actual results may differ from those set forth in the forward-looking statements. Except as required by applicable law, Cerecor expressly disclaims any obligations or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Cerecors expectations with respect thereto or any change in events, conditions or circumstances on which any statement is based.

For media and investor inquiries for Cerecor, Inc.

James Harrell,Investor RelationsChief Commercial OfficerCerecor Inc.jharrell@cerecor.com623.439.2220 office

For media and investor inquiries for Myriad Genetics, Inc.

Scott GleasonSVP of Investor Relations and Corporate StrategyMyriad Genetics, Inc.sgleason@myriad.com801.584.1143 office

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