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Archive - Sep 2020

Date

September 30th

HPV Vaccine Proves Effective in Preventing Cervical Cancer; Girls Vaccinated Before Age 17 Show 88% Reduction in Cervical Cancer; “Data Strongly Supports Continuing HPV Vaccinations of Children and Adolescents Through National Vaccination Programs"

Women vaccinated against HPV (human papilloma virus) have a significantly lower risk of developing cervical cancer, and the positive effect is most pronounced for women vaccinated at a young age. That is according to results of a large study by researchers at Karolinska Institutet in Sweden published online on September 30, 2020 in the New England Journal of Medicine. The article is titled “HPV Vaccination and Risk of Invasive Cervical Cancer." “This is the first time that we, on a population level, are able to show that HPV vaccination is protective not only against cellular changes that can be precursors to cervical cancer, but also against actual invasive cervical cancer," says Jiayao Lei (at right in photo), PhD, researcher at the Department of Medical Epidemiology and Biostatistics at Sweden’s Karolinska Institutet and the study's corresponding author. "It is something we have long suspected but that we are now able to show in a large national study linking HPV vaccination and development of cervical cancer at the individual level." HPV is a group of viruses that commonly causes genital warts and different types of cancer, including cervical cancer, a disease that globally kills more than 250,000 women a year. More than 100 countries have implemented national vaccination programs against HPV, and Sweden, as of August 2020, also includes boys in this program. Previous studies have shown that HPV vaccine protects against HVP infection, genital warts, and precancerous cervical lesions that could develop into cancer of the cervix. However, there is lack of large population-based studies that, on an individual level, have studied the link between HPV vaccine and so-called invasive cervical cancer, which is the most severe form of the disease.

Major Genetic Risk Factor for COVID-19 Inherited from Neanderthals, Study Suggests

Since first appearing in late 2019, the novel virus, SARS-CoV-2, has had a range of impacts on those it infects. Some people become severely ill with COVID-19, the disease caused by the virus, and require hospitalization, whereas others have mild symptoms or are even asymptomatic. There are several factors that influence a person's susceptibility to having a severe reaction, such as their age and the existence of other medical conditions. But one's genetics also plays a role, and, over the last few months, research by the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/) has shown that genetic variants in one region on chromosome 3 impose a larger risk. Now, a new study, published online on September 30, 2020 in Nature (https://www.nature.com/articles/s41586-020-2818-3), has revealed that this genetic region is almost identical to that of a 50,000-year old Neanderthal from southern Europe. Further analysis has shown that, through interbreeding, the variants came over to the ancestors of modern humans about 60,000 years ago. The Nature article is titled “The Major Genetic Risk Factor for Severe COVID-19 Is Inherited From Neanderthals.” "It Is Striking That The Genetic Heritage From Neanderthals has such tragic consequences during the current pandemic," said Professor Svante Pääbo, who leads the Human Evolutionary Genomics Unit (https://groups.oist.jp/heg) at the Okinawa Institute of Science and Technology Graduate University (OIST). Chromosomes are tiny structures that are found in the nucleus of cells and carry an organism's genetic material. They come in pairs with one chromosome in each pair inherited from each parent. Humans have 23 of these pairs.

Regeneron's REGN-COV2 Antibody Cocktail Reduced SARS-CoV-2 Viral Levels and Improved Symptoms in Non-Hospitalized COVID-19 Patients, Report States

On September 29, 2020, Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced the first data from a descriptive analysis of a seamless Phase 1/2/3 trial of its investigational antibody cocktail REGN-COV2, showing it reduced viral load and the time to alleviate symptoms in non-hospitalized patients with COVID-19. REGN-COV2 also showed positive trends in reducing medical visits. The ongoing, randomized, double-blind trial measures the effect of adding REGN-COV2 to usual standard-of-care, compared to adding placebo to standard-of-care. This trial is part of a larger program that also includes studies of REGN-COV2 for the treatment of hospitalized patients, and for prevention of infection in people who have been exposed to COVID-19 patients. "After months of incredibly hard work by our talented team, we are extremely gratified to see that Regeneron's antibody cocktail REGN-COV2 rapidly reduced viral load and associated symptoms in infected COVID-19 patients," said George D. Yancopoulos, MD, PhD, President and Chief Scientific Officer of Regeneron. "The greatest treatment benefit was in patients who had not mounted their own effective immune response, suggesting that REGN-COV2 could provide a therapeutic substitute for the naturally-occurring immune response. These patients were less likely to clear the virus on their own, and were at greater risk for prolonged symptoms. We are highly encouraged by the robust and consistent nature of these initial data, as well as the emerging well-tolerated safety profile, and we have begun discussing our findings with regulatory authorities while continuing our ongoing trials. In addition to having positive implications for REGN-COV2 trials and those of other antibody therapies, these data also support the promise of vaccines targeting the SARS-CoV-2 spike protein."

September 29th

Researchers Identify Epigenetic Drivers for Late-Onset Alzheimer's Disease

New findings suggest that late-onset Alzheimer's Disease is driven by epigenetic changes--how and when certain genes are turned on and off--in the brain. The results were published online on September 28, 2020 in Nature Genetics. The article is titled “An Integrated Multi-Omics Approach Identifies Epigenetic Alterations Associated with Alzheimer’s Disease.” Research led by Raffaella Nativio, PhD, a former Research Associate at Epigenetics, Shelley Berger, PhD, a Professor of Genetics, Biology and Cell and Developmental Biology and Director of the Epigenetics Institute, and Nancy Bonini, PhD, a Professor of Biology and Cell and Developmental Biology, all in the Perelman School of Medicine at the University of Pennsylvania, used post-mortem brain tissue to compare healthy younger and older brain cells to those with Alzheimer's Disease. The team found evidence that epigenetic regulators disable protective pathways and enable pro-disease pathways in those with the disease. "The last five years have seen great efforts to develop therapeutics to treat Alzheimer's disease, but, sadly, they have failed in the clinic to treat humans suffering from this horrible disease," Dr. Berger said. "We are trying a completely different approach to reveal the critical changes in brain cells, and our findings show epigenetic changes are driving disease." Epigenetic changes alter gene expression without DNA mutation, but rather by virtue of marking proteins that package and protect DNA, called histones. Dr. Berger added, "the activity of epigenetic regulators can be inhibited by drugs, and hence we are excited that this may be an Achilles' heel of Alzheimer's that can be attacked by new therapeutics."

VirScan Tool Offers New Insights into COVID-19 Antibody Response; Test Reveals 800 Antigenic Sites (Epitopes) in SARS-CoV-2; Results May Inform COVID-19 Vaccine Refinement and Treatment

A tool designed to detect viral history in a drop of blood has gotten an upgrade in the age of COVID-19. VirScan, a technology that can determine which of more than 1,000 different viruses have infected a person, can now also detect evidence of infection from coronaviruses, including SARS-CoV-2. In a paper published online on September 29, 2020 in Science (https://science.sciencemag.org/content/early/2020/09/28/science.abd4250), investigators from Brigham and Women's Hospital and Harvard Medical School (HMS) offer up a treasure trove of details about the antibody response to SARS-CoV-2 and how this response may differ in individuals who go on to have a more severe case of COVID-19. The article is titled “"Viral Epitope Profiling of COVID-19 Patients Reveals Cross-Reactivity and Correlates of Severity." This may be the deepest serological analysis of any virus in terms of resolution," said corresponding author Stephen Elledge, PhD, the Gregor Mendel Professor of Genetics at the Brigham and HMS. "We now understand much, much more about the antibodies generated in response to SARS-CoV-2 and how frequently they are made. The next question is, what do those antibodies do? We need to identify which antibodies have an inhibitory capacity or which, if any, may promote the virus and actually help it enter into immune cells." In their analysis, Dr. Elledge and colleagues looked in depth at antibody responses to SARS CoV-2 by using VirScan to analyze blood samples from 232 COVID-19 patients and 190 pre-COVID-19 era controls. The team identified 800 sites of the virus that the immune system can recognize, known as epitopes. Not all epitopes are created equal; some may be recognized by neutralizing antibodies, which can elicit a response that eliminates the infection.

ILIAS Biologics, Closes $20.6 Million Series B Financing; ILIAS Is Exosome-Based Therapeutics Company in South Korea; Company Has Technology for Loading Protein into Lumen of Exosomes

On September 28, 2020, ILIAS Biologics Inc., a leading exosome-based therapeutics company in Daejeon, South Korea, announced today that the Company has completed a Series B financing round of $20.6 million in South Korea. The initial investors from the Series A round, HB Investment, Timefolio Asset Management, and Daedeok Venture Partners joined this round with follow-on investment. The new institutional investors, including Asset One, Devsisters Ventures, Meritz Securities, Kiwoom Securities, Daishin Securities, Hanyang Securities/Yeolim Partners, and Genie Asset Management joined this round along with a small number of private investors. ILIAS has raised a total of $40.2 million of capital since its foundation in November 2015. This financing will support the continued development of ILIAS's proprietary EXPLOR® (Exosome engineering for Protein Loading via Optically Reversible protein–protein interaction) platform technology and the advancement of exosome-based therapeutics pipeline. ILIAS recently published promising preclinical data on its lead therapeutic candidate, ILB-202, in Science Advances, and secured a key exosome engineering patent from the United States Patent and Trademark Office (USPTO) in July. While the Company plans to submit the IND application to U.S. FDA and initiate the first-in-human clinical trial by the second half of 2021 targeting an undisclosed acute inflammatory disease, it is also in active discussion with multiple pharmaceutical companies for potential research collaborations.

Sarepta Therapeutics Announces That Its Investigational Gene Therapy SRP-9003 for the Treatment of Limb-Girdle Muscular Dystrophy Type 2E (LGMD2E) Shows Sustained Functional Improvements 18-Months After Administration

On September 28, 2020, Sarepta Therapeutics, Inc. (NASDAQ:SRPT) (http://www.sarepta.com), a leader in precision genetic medicine for rare diseases, announced positive results from the ongoing study of SRP-9003 (rAAVrh74.MHCK7.hSGCB), the Company’s investigational gene therapy for limb-girdle muscular dystrophy Type 2E (LGMD2E). Results included 18-month functional data from three clinical trial participants in the low-dose cohort and 6-month functional data from three participants in the high-dose cohort. SRP-9003 is in development for the treatment of LGMD2E (also known as beta-sarcoglycanopathy and LGMDR4), a devastating monogenic neuromuscular disease caused by a lack of beta-sarcoglycan proteins. SRP-9003 is a gene construct that transduces skeletal and cardiac muscle, delivering a gene that codes for the full-length beta-sarcoglycan protein (https://en.wikipedia.org/wiki/Sarcoglycan), the absence of which is the sole cause of the progressive degeneration and a shortened lifespan characterized by the disease. “There are currently no approved treatments for people with LGMD2E--a disease that causes significant disability in children and often leads to early mortality. It’s very encouraging that we continue to see consistent, positive data from our investigational gene therapy SRP-9003 across several measures, as we know the community needs more options,” said Louise Rodino-Klapac, PhD, Senior Vice President of Gene Therapy, Sarepta Therapeutics. “The improvements in functional measures at 18-months and 6- months in participants from both cohorts who received SRP-9003 are distinctly different from what an age-matched, natural history group would predict with LGMD2E.

September 28th

Fine-Tuning Metabolism of Hair Follicle Stem Cells May Prevent Hair Loss

A team of researchers from Cologne and Helsinki has discovered a mechanism that prevents hair loss: hair follicle stem cells, essential for hair to regrow, can prolong their life by switching their metabolic state in response to low oxygen concentration in the tissue. The research team was led by Associate Professor Sara Wickström (University of Helsinki and Max Planck Institute for the Biology of Ageing) and the dermatologist Professor Sabine Eming (University of Cologne), and included scientists from the University of Cologne's Cluster of Excellence in Aging Research CECAD, the Max Planck Institute for the Biology of Ageing, Collaborative Research Centre 829 “Molecular Mechanisms Regulating Skin Homeostasis,” the Center for Molecular Medicine (CMMC) (all in Cologne), and the University of Helsinki. The paper “Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle” was published online on September 8, 2020 in Cell Metabolism (https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30424-1). Every day, tissues such as the skin and its hair follicles are exposed to environmental damage like ultraviolet radiation. Damaged material is continuously removed and renewed. On average, 500 million cells and 100 hairs are shed every day, amounting to 1.5 grams of material. The dead material is replaced by stem cells, which are specialized, highly proliferative, and long-lived. Tissue function relies on the activity and health of these stem cells; compromised function or reduced number leads to aging. “Although the critical role of stem cells in aging is established, little is known about the mechanisms that regulate the long-term maintenance of these important cells.

Scientists ID Gene Family Key to Unlocking Vertebrate Evolution

New University of Colorado Boulder (CU-Boulder)-led research finds that the traits that make vertebrates distinct from invertebrates were made possible by the emergence of a new set of genes 500 million years ago, documenting an important episode in evolution when new genes played a significant role in the evolution of novel traits in vertebrates. The findings, published online on September 16, 2020 in Nature, show that a gene family only found in vertebrates is critical for forming the head skeleton and other traits unique to vertebrates during embryonic development. The article is titled “Evolution of the Endothelin Pathway Drove Neural Crest Cell Diversification.” "Every animal essentially has the same basic core set of Lego pieces to make them. What this paper shows is that vertebrates have a few special pieces in addition to that, and we identify those special pieces," said Daniel Medeiros, PhD, senior author of the paper and Associate Professor of Ecology and Evolutionary Biology. These special pieces in vertebrates are known as the “endothelin signaling pathway,” a set of genes that influence how cells talk to each other. The researchers found this gene family is responsible for allowing neural crest cells--cells that develop into unique vertebrate traits like skeletal parts, pigment cells, and our peripheral nervous system--to proliferate and specialize into different roles throughout the body. Evolutionary theories have given weight to the role of genome duplication in the evolution of new traits, and for good reason. When a genome duplicates, new copies of existing genes can take on new roles in an organism. But because previous ideas were based mostly on observation, Dr.

Ensign Wasp Has Likely Been Killing Cockroaches for at Least 25 Million Years

An Oregon State University (OSU) study has identified four new species of parasitic, cockroach-killing ensign wasps that became encased in tree resin 25 million years ago and were preserved as the resin fossilized into amber. "Some species of ensign wasps have even been used to control cockroaches in buildings," OSU researcher George Poinar Jr., PhD, said. "The wasps sometimes are called the harbingers of cockroaches--if you see ensign wasps you know there are at least a few cockroaches around. Our study shows these wasps were around some 20 or 30 million years ago, with probably the same behavioral patterns regarding cockroaches." Ensign wasps, of the Hymenoptera order and scientifically known as Evaniidae, earned their common name because their abdomen resembles a flag; an ensign is a large flag on a ship, usually flown at the stern or rear of the vessel, that indicates the ship's nationality. "As the wasps move about, their 'ensign' is constantly moving up and down as if they are flag-waving," said Dr. Poinar, Professor Emeritus in the OSU College of Science and an international expert in using plant and animal life forms trapped in amber to learn more about the biology and ecology of the distant past. About 400 species of ensign wasps exist today, distributed across 20 genera. The wasps live everywhere except polar regions. They typically measure 5 to 7 millimeters in length and don't sting, or bite but are lethal for unhatched cockroaches. A female ensign wasp will look for cockroach egg cases, known as ootheca, and lay an egg on or in one of the cockroach eggs inside the case. When the wasp egg hatches, the larva eats the cockroach egg where it was laid.