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Archive - 2020

Date

May 14th

New Mass Spec Technique (mePROD) Enables Discovery of Potential Targets for COVID-19 Therapy; In Cell Culture Model, Several Already-Approved Drugs Stop SARS-Cov-2 Virus; Multiple Clinical Trial Preparations Now Underway; Article Published in Nature

A team of biochemists and virologists at Goethe University Frankfurt and the Frankfurt University Hospital in Germany were able to observe how human cells change upon infection with SARS-CoV-2, the virus causing COVID-19 in people. The scientists tested a series of compounds in laboratory models and found some that slowed down or stopped virus reproduction. These results, published online on May 14, 2020 in Nature (https://www.nature.com/articles/s41586-020-2332-7_reference.pdf), have enabled the search for an active substance to be narrowed down to a small number of already approved drugs. The Nature article is titled “Proteomics of SARS-CoV-2-Infected Host Cells Reveals Therapy Targets.” Based on these findings, a US company (Moleculin Biotech) reports that it is preparing clinical trials. A Canadian company (Bausch Health Americas) is also starting a clinical study with a different substance. Since the start of February, the Medical Virology Department of the Frankfurt University Hospital has been in possession of a SARS-CoV-2 infection cell culture system. The Frankfurt scientists in Professor Sandra Ciesek's (photo) team succeeded in cultivating the virus in colon cells from swabs taken from two infected individuals returning from Wuhan (https://www.nejm.org/doi/full/10.1056/NEJMc2001899). Using a technique developed at the Institute for Biochemistry II at Goethe University Frankfurt, researchers from both institutions were, together, able to show how a SARS-CoV-2 infection changes the human host cells.

Ticking Time Bomb: Malaria Plasmodium Parasite Has Its Own Inherent Clock, Takahashi-Led Study at UTSW Suggests; New Research Could Lead to ID of Targets to Fight Deadly Disease

The activity of the parasite that causes malaria is driven by the parasite’s own inherent clock, new research led by University of Texas (UT) Southwestern (UTSW) scientists suggests. The findings, published in the May 15, 2020 issue of Science (https://science.sciencemag.org/content/368/6492/746), together with those in a related article by another group also published in the same issue of Science (https://science.sciencemag.org/content/368/6492/754.full), could lead to new ways to fight this pervasive and deadly disease. More than 200 million people contract malaria worldwide each year, and over 400,000 people die annually of this disease, according to statistics from the World Health Organization (WHO). Caused by protozoa in the genus Plasmodium, malaria kills mostly children, with the majority of deaths in sub-Saharan Africa. It has long been known that malaria induces cyclical fevers, which occur every two to three days in human hosts, depending on the species of infecting organism. This is the result of all the parasites simultaneously bursting the red blood cells of the host they infect. “Together, these and other behavioral phenomena suggest that Plasmodium has a sense of time,” says study leader Joseph S. Takahashi (photo), Ph.D. Chair of Neuroscience at UTSW and a Howard Hughes Medical Institute (HHMI) Investigator (https://profiles.utsouthwestern.edu/profile/105885/joseph-takahashi.html). “But the reason for these daily rhythms has been mysterious.”

Malaria Parasite Ticks to Its Own Internal Clock, According to Duke-Led Study Published in Science; Research Could Lead to New Drugs Against Disease That Threatens Half World's Population

When a person gets malaria, a rhythmic dance takes place inside his or her body. The disease's telltale signs -- cyclical fevers and chills -- are caused by successive broods of parasites multiplying in synchrony inside red blood cells, then bursting out in unison every few days. Now, a study shows that even when grown outside the body, malaria parasites can still keep a beat. Reporting in the May 15, 2020 issue of Science, Duke researchers and collaborators have uncovered rhythms in the parasite's gene activity levels that don't rely on time cues from the host, but instead are coordinated from within the parasite itself. The Science article is titled “An Intrinsic Oscillator Drives the Blood Stage Cycle of the Malaria Parasite, Plasmodium falciparum” (https://science.sciencemag.org/content/368/6492/754). The findings indicate that the parasite that causes malaria has its own time-keeping machinery, an internal metronome that ticks of its own accord and causes thousands of parasite genes to ramp up and down at regular intervals. "Malaria has all the molecular signatures of a clock," said Duke biology professor Steven Haase, PhD, the lead author of the study. Understanding how malaria's clock works might help scientists develop new weapons against a disease that kills a child every two minutes, and has proven increasingly resistant to existing drugs, Dr. Haase said. Dr. Haase has spent years studying cell cycles in yeast to understand controls on the timing of events as one cell becomes two, but only recently has he turned to malaria. The work was prompted by a question that has vexed scientists: how do the parasites keep time?

Dynamic Electric Stimulation of Visual Cortex Via Electrodes Produces Vision of Shapes and Identification of Letters in Sighted and Blind Humans; Baylor Study Reported in Cell

For most adults who lose their vision, blindness results from damage to the eyes or optic nerve while the brain remains intact. For decades, researchers have proposed developing a device that could restore sight by bypassing damaged eyes and delivering visual information from a camera directly to the brain. In a paper published in Cell on May 14, 2020, a team of investigators at Baylor College of Medicine in Houston, Texas, report that they are one step closer to this goal. The open-access Cell article is titled "Dynamic Stimulation of Visual Cortex Produces Form Vision in Sighted and Blind Humans." The authors describe an approach in which implanted electrodes are stimulated in a dynamic sequence, essentially "tracing" shapes on the surface of the visual cortex that participants were able to "see." "When we used electrical stimulation to dynamically trace letters directly on patients' brains, they were able to 'see' the intended letter shapes and could correctly identify different letters," said senior author Daniel Yoshor (at right in photo), MD, Chairman of Neurosurgery at Baylor College of Medicine (https://www.bcm.edu/news/appointments-faculty-staff/dr-daniel-yoshor-nam...). "They described seeing glowing spots or lines forming the letters, like skywriting." Previous attempts to stimulate the visual cortex have been less successful. Earlier methods treated each electrode like a pixel in a visual display, stimulating many of them at the same time. Participants could detect spots of light, but found it hard to discern visual objects or forms. "Rather than trying to build shapes from multiple spots of light, we traced outlines," says first author Michael Beauchamp, PhD (https://www.bcm.edu/research/labs/michael-beauchamp).

How “Dark Matter” Non-Coding Regions of Genome Affect Inflammatory Diseases; Deletion of Enhancer Element for GARP in Regulatory T-Cells (Tregs) Causes Uncontrolled Response to Triggered Inflammation of Colon Lining; GARP Is Promising New Drug Target

A study led by researchers at the Babraham Institute, in collaboration with scientists at the Wellcome Sanger Institute, has uncovered how variations in a non-protein-coding “dark matter” region of the genome could make patients susceptible to complex autoimmune and allergic diseases such as inflammatory bowel disease. The study in mice and human cells reveals a key genetic switch that helps immune responses remain in check. Published on May 13, 2020 in Nature, the research, involving collaborations with research institutions in the UK and worldwide, identifies a new potential therapeutic target for the treatment of inflammatory diseases. The Nature article is titled “A Distal Enhancer At Risk Locus 11q13.5 Promotes Suppression of Colitis By Treg Cells.” Over the last twenty years, the genetic basis of susceptibility to complex autoimmune and allergic diseases, such as Crohn's disease, ulcerative colitis, type 1 diabetes, and asthma, has been narrowed down to a particular region of chromosome 11. This work has involved large-scale genome-wide association studies (GWAS), a genome-wide “spot-the-difference” comparison between the genomes of individuals with or without a disease, to highlight regions of variation in the DNA code. This can identify potential genetic causes, and reveal possible drug targets. However, most of the genetic variations responsible for the susceptibility to complex immune and allergic diseases are concentrated within regions of the genome that don't encode proteins - the genome's so-called “dark matter.” This means there is not always a clear gene target for further investigation and the development of treatments.

ENHANCERS

May 13th

Cats Can Infect Other Cats with Virus That Causes COVID-19: Cats In Lab Study Showed No Symptoms; Still No Evidence of Pets Spreading COVID-19 to Humans; Guidelines for Safe Pet Care Noted; UW-Madison and U of Tokyo Involved in NEJM-Published Study

Three cats infected with the virus that causes COVID-19 spread the virus to three other cats in a lab study reported in The New England Journal of Medicine (NEJM) (https://www.nejm.org/doi/full/10.1056/NEJMc2013400) by a research team working in Tokyo, Japan, and Madison, Wisconsin, USA. The open-access article was published on May 13, 2020, and is titled “Transmission of SARS-CoV-2 in Domestic Cats.” The authors included Peter J. Halfnmann, PhD, Masato Hatta, DVM, PhD, Shiho Chib, PhD, Tadashi Maemura, DVM, PhD, and Shufang Fan, PhD, at the University of Wisconsin-Madison; Makoto Takeda, MD, PhD, at the National Institutes of Infectious Diseases, Tokyo, Japan; Noriko Kinoshita, MD, and Shin-ichiro Hattori, PhD, at the National Center for Global Health and Medicine,Tokyo, Japan; and Yuko Sakai-Tagawa, PhD, Kiyoko Iwatsuki-Horimoto, DVM, PhD, Masaki Imai, DVM, PhD, and Yoshihiro Kawaoka, DVM, PhD, at the University of Tokyo, Japan. The research team emphasized that there is no evidence of the COVID-19 virus transmitting from cats to humans. The researchers stated that it is much more likely that humans are giving the virus to their pets, rather than pets causing humans to become sick. The research team infected three cats with large doses of the virus (SARS-CoV-2) that causes COVID-19, directly into both eyes, both nostrils, the mouth, and the trachea (windpipe). The infected cats were housed in pairs with uninfected cats, sharing the same space, food, water, and air. Within five days, the uninfected cats tested positive for SARS-CoV-2 in nasal swabs.

Pregnant Women Are Not at Greater Risk of Severe COVID-19 Than Other Women, According to Results Reported in Pre-Print from University of Oxford & Collaborating Institutions

Researchers from the University of Oxford, in collaboration with the Royal College of Obstetricians and Gynecologists, the Universities of Leeds and Birmingham, and Kings and Imperial Colleges London, have published new research that suggests that pregnant women are no more likely to become ill with severe COVID-19 than non-pregnant woman. However, the majority of women who did become severely ill were in their third trimester of pregnancy, emphasizing the importance of social distancing for this group. The study, published on May 12, 2020 as a pre-print, looked at 427 pregnant women admitted to hospitals in the UK between March 1, 2020 and April 14, 2020 with confirmed COVID-19 (4.9 women out of every 1,000 pregnant women, suggesting pregnant women are not at a higher risk of experiencing severe illness). Information for the study was collected from all 194 hospitals in the UK with a consultant-led maternity unit. Pregnant women from black and ethnic minority backgrounds were more likely to be admitted to hospital for COVID-19. This inequality persisted even when women from London, the West Midlands, and the North West were excluded from the analysis, meaning the difference cannot be explained by higher rates of COVID-19 infection in those areas. The analysis also showed that older pregnant women, those who were overweight or obese, and pregnant women who had pre-existing medical problems, such as high blood pressure and diabetes, were more likely to be admitted to hospital with the infection. Women who were admitted to hospital with COVID-19 in pregnancy were less likely to smoke than a group of comparison pregnant women. Other important findings from the study includethe following.

CytoDyn Completes Submission of All Remaining Parts of Biologics License Application (BLA) for Lernlimab As Part of Combination Therapy for HIV on May 11, 2020

On May 13, 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, confirmed that it had submitted all remaining parts of the Company’s Biologics License Application (“BLA”) for leronlimab as a combination therapy with HAART for highly treatment-experienced HIV patients to the U.S. Food and Drug Administration (FDA) on May 11, 2020. Pursuant to FDA guidelines, CytoDyn informed the FDA it had submitted a complete BLA for rolling review. As a next step, the FDA will start reviewing the BLA for completeness and will make a filing decision. After the BLA submission is deemed completed, the FDA assigns a Prescription Drug User Fee Act (PDUFA) goal date. CytoDyn has Fast Track designation for leronlimab and a rolling review for its BLA, as previously assigned by the FDA, and the company plans to request a priority review for the BLA. A priority review designation, if granted, means the FDA’s goal is to take action on the application within six months of receipt (compared with 10 months under standard review).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. COVID-19 typically transmits person to person through respiratory droplets, commonly resulting from coughing, sneezing, and close personal contact.

May 12th

Tiny RNAs That Should Attack Coronavirus Diminish with Age & Co-Morbidities; Age- and Disease-Associated Decline in Virus-Fighting MicroRNAs May Play Key Role in Increased Disease Presentation and Mortality Rate in Elderly COVID-19 Patients

A group of tiny RNAs that should attack the virus causing COVID-19 when it tries to infect the body are diminished with age and chronic health problems, a decrease that likely helps explain why older individuals and those with preexisting medical conditions are vulnerable populations, investigators report. MicroRNAs (miRNAs) play a big role in our body in controlling gene expression, and also are a front line when viruses invade, latching onto and cutting the RNA, the genetic material of the virus, says Sadanand Fulzele, PhD, Aging Researcher in the Department of Medicine and Center for Healthy Aging at the Medical College of Georgia (MCG) at Augusta University. But with age and some chronic medical conditions, the attacking microRNA numbers dwindle, reducing our ability to respond to viruses, says Dr. Carlos M. Isales, MD, Co-Director of the MCG Center for Healthy Aging and Chief of the MCG Division of Endocrinology, Diabetes, and Metabolism. Much like not having enough troops on the ground in an actual war, the coronavirus is then better able to do what it does naturally, which is hijack our cell machinery so it can replicate, say the researchers who report, with collaborators, in an article published online for the June 2020 issue of Aging and Disease what appear to be key microRNAs involved in responding to this virus. They have a longer-term goal of identifying the biggest hitters and replenishing those troops.

Moderna Receives FDA "Fast Track" Designation for mRNA Vaccine (mRNA-1273) Against COVID-19; Company Finalizing Protocol for Phase 3 Study of mRNA-1273, Expected to Begin in Early Summer of 2020

On May 12, 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 that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the company’s mRNA vaccine candidate (mRNA-1273) against the novel coronavirus (SARS-CoV-2). “Fast Track designation underscores the urgent need for a vaccine against the novel coronavirus,” said Tal Zaks, MD, PhD, Chief Medical Officer at Moderna. “As we await the full set of clinical data from the NIAID-led Phase 1 study, we are actively preparing for our Phase 2 and Phase 3 clinical studies to continue learning about the potential of mRNA-1273 to protect against SARS-CoV-2.” Fast Track is designed to facilitate the development and expedite the review of therapies and vaccines for serious conditions and fill an unmet medical need. Programs with Fast Track designation may benefit from early and frequent communication with the FDA, in addition to a rolling submission of the marketing application. Moderna previously received Fast Track designation for its investigational Zika vaccine (mRNA-1893) and its methylmalonic acidemia (MMA; mRNA-3704) and propionic acidemia (PA; mRNA-3927) programs. On May 6, the U.S. Food and Drug Administration (FDA) completed its review of the Moderna’s Investigational New Drug (IND) application for mRNA-1273, allowing it to proceed to a Phase 2 study, which is expected to begin shortly. Moderna is finalizing the protocol for a Phase 3 study, expected to begin in early summer of 2020. Funding from the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S.