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Self-Corrective Mechanism at Synapse Doubles Lifespan in Mouse Model of ALS (Lou Gehrig’s Disease), Suggests New Approach to Therapy for Human Brain Diseases

A common feature of neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) (also called Lou Gehrig’s disease) is the progressive loss of synapses – the anatomical sites of communication between brain cells – throughout the brain and spinal cord. Typically, synapse loss becomes pervasive before the outward appearance of symptoms of disease, such as memory loss or paralysis. The fact that there must be extensive synapse loss before brain function begins to seriously decline suggests that the nervous system maintains a deep functional reserve that keeps everything working normally until the damage passes a tipping point and the brain’s resilience begins to break down. But how exactly does this functional reserve confer resilience in the face of ongoing brain degeneration? Could differences in this reserve explain why some individuals with ALS decline and die within months, while others – like astrophysicist Steven Hawking (photo)--live for decades? And could a treatment that boosts this functional reserve help more patients survive and prosper as long as Hawking? In a new study, published online on May 6, 2020 in Neuron (https://www.sciencedirect.com/science/article/abs/pii/S0896627320302786?...), University of California San Francisco (UCSF) neuroscientist Graeme Davis, PhD, and his team have identified a powerful self-corrective mechanism within synapses that is activated by neurodegeneration and acts to slow down disease progression in animal models of ALS. Selectively eliminating this self-corrective mechanism dramatically accelerated progression of ALS in mice, shortening their lifespan by 50 percent.

Coordinated Strategy to Accelerate Multiple COVID-19 Vaccine Candidates Is Key, NIH Director Francis Collins & NIAID Director Anthony Fauci Say

A harmonized and collaborative approach to the clinical testing, scale-up, and distribution of candidate vaccines to prevent COVID-19 is essential, scientific leaders write in a Policy Forum piece published online on May 11, 2020 in Science. The open-access article is titled “A Strategic Approach to COVID-19 Vaccine R&D.” As the COVID-19 pandemic continues, government, industry, and academia have introduced a variety of vaccine candidates. The authors note that more than one effective vaccine approach likely will be required to successfully protect the global community from SARS-CoV-2, the virus that causes COVID-19. They describe a strategic approach to research and development that would generate essential data for multiple vaccine candidates in parallel. NIH Director Francis S. Collins, MD,PhD; NIAID Director Anthony S. Fauci, MD; Lawrence Corey, MD, Professor in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center in Seattle; and John R. Mascola, MD, Director of NIAID’s Vaccine Research Center are the co-authors of the Policy Forum article in Science. The open-access article discusses diverse vaccine candidates and key considerations for development, including the characteristics of various vaccine platforms in terms of prior commercial experience, scalability, and the types of immune responses generated. It also emphasizes that no single vaccine or vaccine platform is likely to meet the global need, highlighting the need for a coordinated strategic approach to vaccine development. The authors stress that researchers need to learn more about what constitutes a durable protective immune response against COVID-19.

CytoDyn to Present at Wall Street Reporter’s NEXT SUPERSTOCK Livestream Event on Its Monoclonal Anti-CCR5 Antibody (Leronlimab) for COVID-19, and Also for HIV, Cancer, & Graft Versus Host Disease; Wednesday, May 13, 2020, at 12:30 pm EDT / 9:30 am PDT

On May 11, 2020, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced that Jacob Lalezari, MD, CEO of Quest Clinical Research: Bruce Patterson, MD, Chief Executive Officer and Founder of IncellDx, a diagnostics company, and an advisor to CytoDyn; and Nader Pourhassan, PhD, President and Chief Executive Officer of CytoDyn, will provide a comprehensive business update. The Wall Street Reporter’s event is scheduled for Wednesday, May 13, 2020 at 12:30 pm ET / 9:30 am PT. The presentation will be approximately 15 minutes, followed by a Q&A session of approximately 45 minutes. You may register for the event at the following link (https://attendee.gotowebinar.com/register/8072137589911916560). Interested participants are encouraged to log in early prior to the start of the event, as the online event has a capacity of 3,000 participants. Please note that there will be no telephone access; this is a webcast-only event. The livestream presentation will be archived for 30 days. For anyone unable to attend, a video will be posted on CytoDyn’s website approximately 24 hours after the presentation. The conference sponsor provides corporate visibility services to CytoDyn for a fee. CytoDyn is currently enrolling patients in two clinical trials for COVID-19, a Phase 2 randomized clinical trial for mild-to-moderate COVID-19 population in the U.S. and a Phase 2b/3 randomized clinical trial for severe and critically ill COVID-19 population in several hospitals throughout the country. SARS-CoV-2 was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China. The origin of SARS-CoV-2 causing the COVID-19 disease is uncertain, and the virus is highly contagious.

NIH Clinical Trial Testing Antiviral Remdesivir Plus Anti-Inflammatory Drug Baricitinib for COVID-19 Begins

A randomized, controlled clinical trial evaluating the safety and efficacy of a treatment regimen of the investigational antiviral remdesivir plus the anti-inflammatory drug baricitinib for coronavirus disease 2019 (COVID-19) has begun. The trial is now enrolling hospitalized adults with COVID-19 in the United States. The trial is expected to open at approximately 100 U.S. and international sites. Investigators currently anticipate enrolling more than 1,000 participants.The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring the trial. The clinical trial is the next iteration of NIAID’s Adaptive COVID-19 Treatment Trial (ACTT) (https://www.niaid.nih.gov/news-events/nih-clinical-trial-remdesivir-trea...), which began on February 21 to evaluate remdesivir, an investigational broad-spectrum antiviral treatment developed by Gilead Sciences, Inc. That trial closed to enrollment on April 19 after recruiting 1,063 participants at 47 U.S. and 21 international sites. An independent data and safety monitoring board (DSMB) overseeing the trial met on April 27 and shared their preliminary analysis with the study sponsor, NIAID. Their analysis showed that patients who received remdesivir had a statistically significant shorter time to recovery compared to patients who received placebo (https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivi...). More detailed information about the trial results, including more comprehensive data, will be available in a forthcoming report. In this next trial with baricitinib, called ACTT 2, all participants will receive remdesivir or remdesivir with baricitinib.

Temperature & Latitude Not Associated with COVID-19 Spread, Canadian Study Finds; School Closures, Physical Distancing, and Public Health Measures Do Have Positive Effect

Temperature and latitude do not appear to be associated with the spread of coronavirus disease 2019 (COVID-19), according to a study of many countries published online on May 8, 2020 in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.200920, but school closures and other public health measures are having a positive effect. The article is titled “Impact of climate and public health interventions on the COVID-19 pandemic: A prospective cohort study.” "Our study provides important new evidence, using global data from the COVID-19 epidemic, that these public health interventions have reduced epidemic growth," says Dr. Peter Jüni, Institute for Health Policy, Management and Evaluation, University of Toronto, and St. Michael's Hospital, Toronto, Ontario. The Canadian study looked at 144 geopolitical areas -- states and provinces in Australia, the United States and Canada as well as various countries around the world -- and a total of more than 375,600 confirmed COVID-19 cases. China, Italy, Iran, and South Korea were excluded because the virus was either waning in the case of China or in full disease outbreak at the time of the analysis in others. To estimate epidemic growth, researchers compared the number of cases on March 27 with cases on March 20, 2020, and determined the influence of latitude, temperature, humidity, school closures, restrictions of mass gatherings and social distancing measured during the exposure period of March 7 to 13. They found little or no association between latitude or temperature with epidemic growth of COVID-19 and a weak association between humidity and reduced transmission. The results -- that hotter weather had no effect on the pandemic's progression -- surprised the authors.

Moderna (mRNA Therapeutics & Vaccines) to Present at Upcoming Investor Conferences; Live Webcasts Available: Tuesday, May 12, and Monday, May 18

On May 8, 2020, Moderna, Inc., (Nasdaq: MRNA) a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, announced its participation in the following upcoming investor conferences: Bank of America Securities 2020 Health Care Conference on Tuesday, May 12, 2020 at 2:20 p.m. ET; and UBS Global Healthcare Conference on Monday, May 18, 2020 at 1:20 p.m. ET. A live webcast of each presentation will be available under “Events and Presentations” in the Investors section of the Moderna website at https://investors.modernatx.com/. A replay of each webcast will be archived on Moderna’s website for 30 days following the presentation. Moderna is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. mRNA medicines are designed to direct the body’s cells to produce intracellular, membrane or secreted proteins that can have a therapeutic or preventive benefit and have the potential to address a broad spectrum of diseases. Moderna’s platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, providing the Company the capability to pursue in parallel a robust pipeline of new development candidates. Moderna is developing therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases, and autoimmune and inflammatory diseases, independently and with strategic collaborators. Headquartered in Cambridge, Mass., Moderna currently has strategic alliances for development programs with AstraZeneca PLC and Merck & Co., Inc., as well as the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S.

New York State Department of Health Partnering with New York Genome Center & Rockefeller University on Genome Study to Understand COVID-19 Related Illnesses in Children, Including Those Resembling Kawasaki Disease & Toxic Shock-Like Syndrome

On May 9, 2020, Governor Andrew M. Cuomo announced (https://www.governor.ny.gov/news/governor-cuomo-announces-state-helping-...) that the New York State Department of Health is partnering with the New York Genome Center (NYGC) and The Rockefeller University, both in New York City, to conduct a genome and RNA sequencing study to better understand COVID-19-related illnesses in children. Recently, there have been 73 reported cases with three deaths in New York in children with symptoms similar to Kawasaki disease (https://en.wikipedia.org/wiki/Kawasaki_diseas) and toxic shock-like syndrome (http://www.clinicsinsurgery.com/pdfs_folder/cis-v4-id2619.pdf). The study will involve sequencing samples collected from affected pediatric patients across hospitals in New York State, and actionable results will be shared with the patients’ clinicians. Clinical case review meetings and other multi-institutional collaborations will involve members of the COVID-19 Genomics Research Network (https://covidgenomics.org/about/) organized by the NYGC.

[NYGC press release] [New York Governor's press release] [COVID-19 Genomics Research Center] [New York Genome Center]

Nature Reviews Immunology Publishes Timely Article: “The Trinity of COVID-19: Immunity, Inflammation, and Intervention

In a review article published online on April 28, 2020, scientists from Singapore provide an overview of the pathophysiology of SARS-CoV-2 infection. The researchers describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. The open-access article was published online on April 28, 2020 in Nature Reviews Immunology and is titled “The Trinity of COVID-19: Immunity, Inflammation, and Intervention” (https://www.nature.com/articles/s41577-020-0311-8). The lead author is Matthew Zirui Tay, PhD, of the Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, Singapore; and the senior author is Lisa F. P. Ng (https://en.wikipedia.org/wiki/Lisa_Ng), PhD, of the same organization, and also with affiliations at the Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; and at the Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK. At the end of their review, the authors conclude that “Controlling the inflammatory response may be as important as targeting the virus. Therapies inhibiting viral infection and regulation of dysfunctional immune responses may synergize to block pathologies at multiple steps. At the same time, the association between immune dysfunction and outcome of disease severity in patients with COVID-19 should serve as a note of caution in vaccine development and evaluation. Further studies of the host immune response to SARS-CoV-2 are necessary, including a detailed investigation of the determinants of healthy versus dysfunctional outcomes.

Gene Hunt to Explain Why Some Young, Healthy People Die from COVID-19; Rockefeller Scientists Closely Examine Genetics of Outliers

Early on in its emergence, it became clear that the novel coronavirus is particularly dangerous to older people and those with pre-existing health conditions. But just as there are patterns, there are outliers. As the infection spread around the globe, reports started to pile up of young, previously healthy people whose disease suddenly turned fatal. Finding out what has made this group of people so vulnerable to the infection may be an important step in developing new ways to treat the disease or identify those at high risk. And scientists suspect the answer may be in their genes. “Infectious diseases are always an interplay between a pathogen and the host’s immunity,” says Jean-Laurent Casanova, MD, PhD, Head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University. “At least some of these patients may suffer from a genetic variation that make their host defense particularly vulnerable to SARS-CoV2.” Dr. Casanova, along with Dr. Helen Su at the National Institute of Allergy and Infectious Diseases (NIAID) are leading an international project, the COVID Human Genetic Effort (https://www.covidhge.com/), to comb through the genomes of many COVID-19 outliers in search of any rare gene variant that they may share, and that may explain their body’s insufficient response to the infection. All infections appear to come with what scientists call inter-individual clinical variability, meaning that a fraction of infected people are hit especially hard. With cytomegalovirus, for example, most cases are so mild that the infection goes unnoticed, yet it is often detrimental to fetuses and it kills one in a million infected individuals (https://www.rockefeller.edu/news/27419-unusual-patient-case-cmv-rare-imm...). Tuberculosis, on the other hand, can kill as many as five percent of infected individuals.

Rockefeller Scientists Use “Elite” Antibodies from COVID-19 Survivors to Develop Potent Therapies; An Estimated 5% of Survivors Have Powerful Neutralizing Antibodies to COVID-19; Special Approach Allows ID, Cloning, & Subsequent Mass Production

In the few weeks since New York City came to a socially distanced halt, more than 250 COVID-19 survivors have visited Rockefeller University’s otherwise quiet campus to contribute their blood to science. Here, a group of immunologists, medical scientists, and virologists is betting that a cure for the disease can be created from the antibodies of these previously ill patients. The study is one of nearly 20 COVID-19 projects (https://www.rockefeller.edu/news/27795-rockefeller-launching-covid19-res...) that have been launched by Rockefeller researchers since early March in an effort to better understand the SARS-CoV-2 virus and speed the development of new treatments. The team’s plan is to find the so-called “elite neutralizers,” the minority of people who have conquered the infection so exceptionally that their antibodies have the potential to become drugs. “We are sifting through millions of antibodies made by each person to find which ones actually neutralize the virus,” says Michel C. Nussenzweig, MD, PhD, the Zanvil A. Cohn and Ralph M. Steinman Professor and Head of the Laboratory of Molecular Immunology at The Rockefeller. The project is being led by Dr. Nussenzweig, Dr. Paul Bieniasz, Dr. Marina Caskey, Dr. Theodora Hatziioannou, Dr. Charles M. Rice, and Dr. Davide F. Robbiani. The same approach has shown great potential against other viruses, including HIV, and there are promising signs, even as the study is still recruiting its first waves of donors (http://clinicalstudies.rucares.org/coronavirus.php): i.e., the team has already identified a number of antibodies that are able to block the virus from interacting with its receptor. Those with the best potential will be moved to the next phase of the project, where the researchers will work with industry partners to produce material for clinical testing.

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