Syndicate content

Defects in “Swiss-Army Knife” of Gene Expression May Contribute to Neuronal Diseases Like Alzheimer's & Parkinson’s; Ccr-Not Complex Critical to Controlling Ribosome's Rate of Translating mRNA to Protein

The growth, death, and diseases of complex organisms rely on the flow of information -- from genes in DNA, through their transcription into RNA, and then translation of that transcript into proteins, which in turn build much of the living organism. Proteins that control this whole process are themselves subject to this overarching information flow for survival. Researchers have now discovered a previously unknown function of a group of proteins, called the Ccr4-Not complex (https://www.ncbi.nlm.nih.gov/pubmed/26821858), that may shed light on the development of diseases like Alzheimer's. The findings were published in the April 17, 2020 issue of Science. The article is titled “The Ccr4-Not Complex Monitors the Translating Ribosome for Codon Optimality.” "The Ccr4-Not complex is involved in so many aspects of gene expression that we might as well call it the 'Swiss Army Knife' of protein production," says Toshifumi Inada, PhD, a professor from the Graduate School of Pharmaceutical Sciences at Japan’s Tohoku University, who led the research. The best understood aspect of Ccr4-Not's role is its involvement in the destruction of the messenger RNA (mRNA). The mRNA molecules are like instruction manuals that tell the ribosomes, the cell's protein-making machinery, how to construct proteins. The amount of proteins produced by the ribosomes is crucial, and so is the speed of that production. You don't want too many or too few, too fast or too slow. In turn, these protein levels depend on the amount of mRNA. Thus control of mRNA destruction--especially when these instruction manuals have mistakes in them--is critical in controlling protein production."But, until now, how Ccr4-Not did this has remained elusive," Dr. Inada adds.

“Cytokine Storms” & T-Cell Counts May Offer Clues on How to Treat COVID-19; Study Carried Out on Patients Hospitalized in Wuhan, China

So-called “cytokine storms” may affect the severity of COVID-19 cases by lowering T-cell counts, according to a new study published online on May 1, 2020 in Frontiers in Immunology. The open-access article is titled “Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19).” Researchers studying coronavirus cases in China found that sick patients had a significantly low number of T cells, a type of white blood cell that plays a crucial role in immune response, and that T-cell counts were negatively correlated with case severity. Interestingly, these scientists also found a high concentration of cytokines, a class of proteins that normally helps fight off infection. Too many cytokines can trigger an excessive inflammatory response known as a “cytokine storm,” which causes attacks on healthy cells. The study suggests that coronavirus does not attack T cells directly, but rather triggers the cytokine release, which then drives the depletion and exhaustion of T cells. The findings offer clues on how to target treatment for COVID-19, which has become a worldwide pandemic and a widespread threat to human health in the past few months. "We should pay more attention to T-cell counts and their function, rather than respiratory function of patients," says author Dr. Yongwen Chen of Third Military Medical University in China, adding that "more urgent, early intervention may be required in patients with low T-lymphocyte counts.” Dr. Chen says he and his co-authors became interested in examining T cells when they noticed that many of the patients they treated for COVID-19 had abnormally low numbers of lymphocytes, a type of white blood cell that includes T cells.

CytoDyn Describes Stunning Results for COVID-19 Treatment with Leronlimab; Drug Ends “Cytokine Storms,” Restores Lung Function, & Reduces Plasma Viral Load; Ventilated Patients Achieve Rapid Improvement & Some Can Be Ex-Tubated 48 Hours After Treatment


--Results described in CytoDyn Investor Community Conference Call on Monday, April 27, 2020.
--CytoDyn scientists believe their studies show that powerful immune modulator RANTES drives the pathogenic process of COVID-19.
--RANTES is chemoactive chemokine, expressed by many hematopoietic and non-hematopoietic cell types, that plays key role in controlling homing and migration of effector and memory T-cells during acute infections.
--RANTES receptor (CCR5) is co-receptor for HIV and a major target of anti-HIV drugs based on blocking viral entry.
--RANTES levels are highly elevated in COVID-19 patients and RANTES fundamentally drives the COVID-19 pathogenic process via binding of RANTES to CCR5.
--CytoDyn’s drug, a humanized monoclonal antibody called leronlimab, blocks CCR5, denying binding access to RANTES.
--Levels of RANTES return to normal very quickly after single sub-cutaneous injection of leronlimab
--Disease-associated high levels of interleukin-6, and of other chemokines, are quickly reduced to normal.
--Lung function is restored.
--Plasma viral load is reduced.
--Drug delivered by one subcutaneous injection.

CytoDyn Reports Strong Results from eIND COVID-19 Patients Treated with Leronlimab; Majority of Patients Have Demonstrated Remarkable Recoveries

On Thursday, April 30, 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 updates on 49 COVID-19 patients who have received leronlimab under the U.S. Food and Drug Administration’s (FDA) emergency Investigational New Drug (eIND) program: Eleven (11) Patients in NY hospital: All treated patients were in Intensive Care Units (ICU) because of acute respiratory failure, eight of whom were intubated (placed on mechanical ventilation). One patient was not intubated because of poor baseline pulmonary status (history of lung cancer and had undergone bilateral upper lobectomy). Seven patients were organ-transplant recipients (six patients were renal-transplant recipients and one patient had a history of heart transplant) and were on immunosuppressive regimen. Ten patients were on dialysis and nine were on vasopressors during hospitalization. Despite their pre-existing and severe conditions, we believe we were able to save the lives of four patients. All patient blood samples were evaluated and important, powerful results from the effect of leronlimab were demonstrated in almost all of these patients. This data has been submitted to a prestigious journal and we expect the publication on Friday, May 1; Twenty-three (23) Patients in Southern California Hospital: Six patients were in critical condition (intubated) and 17 patients were severely ill, needing oxygen support. No death was reported. Out of 6 critical patients, all were intubated patients, 3 were extubated (taken off ventilator), 2 patients remain relatively stable and still breathing with the assistance of a ventilator and one patient has shown deterioration in respiratory parameters.

Gilead Announces Results from Phase 3 Trial of Investigational Antiviral Remdesivir in Patients with Severe COVID-19--Study Demonstrates Similar Efficacy with 5- and 10-Day Dosing Durations of Remdesivir

On April 29, Gilead Sciences, Inc. (Nasdaq: GILD) announced topline results from the open-label, Phase 3 SIMPLE trial evaluating 5-day and 10-day dosing durations of the investigational antiviral remdesivir in hospitalized patients with severe manifestations of COVID-19 disease. The study demonstrated that patients receiving a 10-day treatment course of remdesivir achieved similar improvement in clinical status compared with those taking a 5-day treatment course (Odds Ratio: 0.75 [95% CI 0.51 – 1.12] on Day 14). No new safety signals were identified with remdesivir across either treatment group. Gilead plans to submit the full data for publication in a peer-reviewed journal in the coming weeks. “Unlike traditional drug development, we are attempting to evaluate an investigational agent alongside an evolving global pandemic. Multiple concurrent studies are helping inform whether remdesivir is a safe and effective treatment for COVID-19 and how to best utilize the drug,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “These study results complement data from the placebo-controlled study of remdesivir conducted by the National Institute for Allergy and Infectious Diseases (NIAID) and help to determine the optimal duration of treatment with remdesivir. The study demonstrates the potential for some patients to be treated with a 5-day regimen, which could significantly expand the number of patients who could be treated with our current supply of remdesivir. This is particularly important in the setting of a pandemic, to help hospitals and healthcare workers treat more patients in urgent need of care.” Remdesivir is not yet licensed or approved anywhere globally and has not yet been demonstrated to be safe or effective for the treatment of COVID-19.

CytoDyn Submits Completed BLA* to FDA for Leronlimab As Combination Therapy, with HAART, for Highly-Treatment-Experienced HIV Patients; In FDA Review Period, Cytodyn Will Dedicate All Resources to Ensure Availability of Leronlimab for COVID-19 Patients

On Monday, April 27, 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 the Company has submitted the clinical, and the CMC (chemistry, manufacturing and controls) portions of its BLA (*biologics license application) to the FDA for leronlimab as a combination therapy, with HAART (highly active antiretroviral therapy),** for highly-treatment-experienced HIV patients. The FDA previously granted both Fast-Track designation for leronlimab and rolling review for the Company’s BLA in HIV indication. “The submission of the final two parts of the BLA is a significant milestone for the Company, and initiates its transition from a development-stage company to a commercial organization. We are excited about the opportunity to introduce a novel therapeutic to HIV patients. In addition to the BLA submission, once the ongoing investigative trial for leronlimab as a once-weekly monotherapy for HIV-infected patients has reached its objectives, we plan to initiate a registration-directed study. Leronlimab’s strong safety profile demonstrated in eleven clinical trials with over 800 people supports its long-term potential,” said Nader Pourhassan, PhD, President and Chief Executive Officer of CytoDyn. “With the BLA filing for a combination therapy now complete, we are continuing our efforts on commercialization-readiness, as well as advancing leronlimab in the other important therapeutic areas of COVID-19, cancer, and immunology. The BLA filing is a monumental achievement for our Company, and was made possible through the sheer determination and commitment of CytoDyn’s team and the Amarex Clinical Research (https://www.amarexcro.com/services.html) team led by Dr.

Corona Viruses and Bats Have Been Evolving Together for Millions of Years

Different groups of bats have their own unique strains of corona virus. Bats do a lot of good for the world--they pollinate plants, they eat disease-carrying insects, and they help disperse seeds that help with the regeneration of tropical forest trees. Bats and a range of other mammal groups are also natural carriers of corona viruses. To better understand this very diverse family of viruses, which includes the specific corona virus behind COVID-19, scientists compared the different kinds of corona viruses living in 36 bat species from the western Indian Ocean and nearby areas of Africa. They found that different groups of bats at the genus, and in some cases family, level had their own unique strains of corona virus, revealing that bats and corona viruses have been evolving together for millions of years. "We found that there's a deep evolutionary history between bats and corona viruses," says Steve Goodman, PhD, MacArthur Field Biologist at Chicago's Field Museum and an author of a paper just published in Scientific Reports detailing the discovery. "Developing a better understanding of how corona viruses evolved can help us build public health programs in the future." The study was led by Université de La Réunion scientists Léa Joffrin, PhD, and Camille Lebarbenchon, PhD, who conducted the genetic analyses in the laboratory of "Processus Infectieux en Milieu Insulaire Tropical (PIMIT)" on Réunion Island, focusing on emerging infectious diseases on islands in the western Indian Ocean. The open-access Scientific Reports article was published online on April 23, 2020, and is titled “Bat Coronavirus Phylogeography in the Western Indian Ocean.” Many people use "corona virus" as a synonym for "COVID-19," the kind of corona virus causing the current pandemic.

Exosomes Are “Sensational Biological Discovery” with Fantastic Therapeutic Potential, Eminent Yale Immunologist Says in New Review

--Tiny Sub-Cellular Extracellular Vesicles Called Exosomes “Seem to Be Involved in Nearly All Biological & Clinical Processes"
--Huge Medical Potential Is Described
--Author Says Breast Milk Exosomes Are Strongly Resistant to Noxious Environment of Neonatal Stomach & Survive There for Subsequent Intestinal Absorption to Enable Genetic-Based Altering of Developing Functions in Neonates
--Data Demonstrating Successful Allergy Treatment Using Antigen-Specific, Antibody-Enabled Targeting of Acceptor Cells, Coupled with Delivery of Selected Genetic-Function-Altering MicroRNA, Is Presented

The review article describes exosomes (tiny, lipid-membrane-bounded sacs of molecular cargo) as “a sensational biologic discovery” and suggests their huge potential for enabling a wide range of major new applications, including the treatment of many different diseases, and was published online today (April 27, 2020) in Research Open—Microbiology, Immunology, and Pathology (Volume 2, Issue 1) (https://researchopenworld.com/exosome-extracellular-vesicles-a-vehicle-f...). Microbiology, Immunology and Pathology (MIP) is an open access, peer-reviewed journal with broad scope, covering all zones of Microbiology, Immunology, and Pathology.

The new open-access short review article is titled “Exosome Extracellular Vesicles: A Vehicle for Simultaneous Immune and Genetic Therapy,” and was authored by Philip Askenase (photo), MD, Professor of Medicine (Clinical Immunology) at the Yale University School of Medicine in the Section of Rheumatology and Clinical Immunology, and former Chief of Allergy & Clinical Immunology at the Yale University School of Medicine.

The Most Promising Strategies for Defeating Corona Viruses: A Review Study

In an unprecedented effort, hundreds of thousands of researchers and clinicians worldwide are locked in a race against time to develop cures, vaccines, and better diagnostic tests for COVID-19, the illness caused by the virus SARS-CoV-2. Over 1,650 articles on COVID-19 are already listed in databases such as Google Scholar, while dozens more are added daily. The register (htttp://www.ClinicalTrials.gov) lists over 460 ongoing clinical trials on COVID-19, although the majority are still in the earliest stages. Given the diversity of experimental approaches among these studies, a systematic review of possible clinical strategies is timely and welcome. In a new study, aimed at the research community but also comprehensible for non-specialists, experts from the University of North Carolina at Chapel Hill (UNC-Chapel Hill) review possible strategies against dangerous coronaviruses--not only SARS-CoV-2 and its relatives such as SARS-Cov (causing Severe Acute Respiratory Syndrome, SARS) and MERS-Cov (causing Middle East Respiratory Syndrome, MERS), but also as yet unknown strains that will inevitably emerge in the future. The open-accessreview was published online on April 24, 2020 in Frontiers in Microbiology and is titled “The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses.” The authors propose that the most promising approaches for fast progress are selected antivirals such as remdesivir, and gene therapy. "Coronaviruses represent a true threat to human health and the global economy. We must first consider novel counter-measures to control the SARS-Cov-2 pandemic virus and then the vast array of high-threat zoonotic viruses that are poised for human emergence in the future," says Dr. Ralph Baric, William R. Kenan, Jr.

Convalescent Plasma Treatment for COVID-19 Shows Early Promising Results in U Wisconsin (UW) Hospital Study; Asthma & Respiratory Allergies Associated with Reduced Expression of COVID-19 Cell Receptor (ACE2), According to Results of Second UW-Led Study

Two weeks after the first Madison, Wisconsin-area donor contributed convalescent plasma (https://madison.com/wsj/news/local/health-med-fit/first-uw-hospital-covi...) to treat COVID-19 patients at University of Wisconsin (UW) Hospital, 14 patients have been treated, with some showing significant improvement, a doctor said Friday. Plasma from patients who have recovered from COVID-19 that presumably contains anti-COVID-14 antibodies, are being transfused into patients struggling with complications of the disease at UW Hospital and some 40 centers around the country (https://ccpp19.org/). The treatment is experimental, but the approach is hardly new, with so-called convalescent plasma used for more than a century to combat ailments such as the 1918 influenza epidemic, the Ebola virus outbreak, and diseases such as MERS (Middle East Respiratory Syndrome) and SARS (Severe Acute Respiratory Syndrome) caused by other coronaviruses. Approximately 45 recovered patients from Dane County (in which the state capital of Madison is located) have donated plasma, the liquid portion of blood that contains antibodies to fight infections, and others have begun the process to donate, said Dr. William Hartman, a UW Health anesthesiologist heading up UW Hospital’s study. Each donor can help treat two or three patients, and plasma donated locally may be used at UW Hospital or other centers, Dr. Hartman said. People who would like to donate their plasma can learn more by calling 608-262-8300 or emailing uwcovid19project@hslc.wisc.edu.

Syndicate content