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Archive - Oct 2020

October 13th

Simple Sugar (N-Acetylglucosamine) May Be Possible Therapy for Repairing Myelin in Multiple Sclerosis, Study in JBC Suggests

N-acetylglucosamine (image), a simple sugar found in human breast milk and sold as an over-the-counter dietary supplement in the United States, promotes myelin repair in mouse models and correlates with myelination levels in multiple sclerosis patients according to a new University of California, Irvine (UCI)-led study. Published online on September25, 2020 in the Journal of Biological Chemistry, the study also demonstrates that in mice, delivering N-acetylglucosamine orally to lactating mothers drove primary myelination in their nursing offspring. N-acetylglucosamine is a simple sugar that is metabolically attached to proteins at the cell surface to control cellular function. "We found that N-acetylglucosamine activates myelin stem cells to promote primary myelination and myelin repair," said Michael Demetriou, MD, PhD, FRCP(C), Professor of Neurology, Microbiology and Molecular Genetics at the UCI School of Medicine and leader of the study. "Our data raises the intriguing possibility that N-acetylglucosamine may be a simple therapy to promote myelin repair in multiple sclerosis patients". Formal human studies will be required to test this theory. The open-access JBC article is titled “N-Acetylglucosamine Drives Myelination by Triggering Oligodendrocyte Precursor Cell Differentiation.” The failure of robust re-myelination following inflammatory demyelination in multiple sclerosis leads to chronic disability and neurodegeneration. Myelin insulates the long, cable-like nerve cell branches called axons, and serves to increase the speed of electrical signal conduction between neurons. Myelination in the central nervous system also plays an important role in cognitive development during childhood.

October 12th

Genomic Study Reveals Evolutionary Secrets of Banyan Fig Tree’s Aerial Roots and Specific Wasp Pollinator

The banyan fig tree Ficus microcarpa (photo) is famous for its aerial roots, which sprout from branches and eventually reach the soil. The tree also has a unique relationship with a wasp that has coevolved with it and is the only insect that can pollinate it. In a new study, researchers identify regions in the banyan fig's genome that promote the development of its unusual aerial roots and enhance its ability to signal its wasp pollinator. The study, published online on October 8, 2020 in the journal Cell, also identifies a sex-determining region in a related fig tree, Ficus hispida. Unlike F. microcarpa, which produces aerial roots and bears male and female flowers on the same tree, F. hispida produces distinct male and female trees and no aerial roots. The Cell article is titled “Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution.” Understanding the evolutionary history of Ficus species and their wasp pollinators is important because their ability to produce large fruits in a variety of habitats makes them a keystone species in most tropical forests, said Ray Ming, PhD, a Plant Biology Professor at the University of Illinois, Urbana-Champaign who led the study with Jin Chen, PhD, of the Chinese Academy of Sciences. Figs are known to sustain at least 1,200 bird and mammal species. Fig trees were among the earliest domesticated crops and appear as sacred symbols in Hinduism, Buddhism, and other spiritual traditions. The relationship between figs and wasps also presents an intriguing scientific challenge. The body shapes and sizes of the wasps correspond exactly to those of the fig fruits, and each species of fig produces a unique perfume to attract its specific wasp pollinator. To better understand these evolutionary developments, Dr.

Blocking Alternative Complement Pathway with Factor D Inhibitor May Halt COVID-19 Infection & Prevent Severe Organ Damage, Johns Hopkins Study Suggests

While the world waits eagerly for a safe and effective vaccine to prevent infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing the COVID-19 pandemic, researchers also are focusing on better understanding how SARS-CoV-2 attacks the body in the search for other means of stopping its devastating impact. The key to one possibility--blocking a protein that enables the virus to turn the immune system against healthy cells--has been identified in a recent study by a team of Johns Hopkins Medicine researchers. Based on their findings, the researchers believe that inhibiting the protein, known as factor D (image), also will curtail the potentially deadly inflammatory reactions that many patients have to the virus. Making the discovery even more exciting is the fact that there may already be drugs in development and testing for other diseases that can do the required blocking. The study was published online on September 2, 2020, in Blood. The open-access article is titled “Direct Activation of the Alternative Complement Pathway by SARS-CoV-2 Spike Proteins Is Blocked by Factor D Inhibition.” Scientists already know that spike proteins on the surface of the SARS-CoV-2 virus are the means by which it attaches to cells targeted for infection. To do this, the spikes first grab hold of heparan sulfate, a large, complex sugar molecule found on the surfaces of cells in the lungs, blood vessels, and smooth muscle making up most organs. Facilitated by its initial binding with heparan sulfate, SARS-CoV-2 then uses another cell-surface component, the protein known as angiotensin-converting enzyme 2 (ACE2), as its doorway into the attacked cell. The Johns Hopkins Medicine team discovered that when SARS-CoV-2 ties up heparan sulfate, it prevents factor H from using the sugar molecule to bind with cells.

October 7th

Nobel Prize in Chemistry 2020 Awarded for Monumental Discovery of CRISPR/Cas9 Genome Editing by Emmanuelle Charpentier and Jennifer Doudna

On October 7, 2020, it was announced that The Royal Swedish Academy of Sciences has awarded the Nobel Prize in Chemistry 2020 jointly to Emmanuelle Charpentier, PhD, Max Planck Unit for the Science of Pathogens, Berlin, Germany and Jennifer A. Doudna, PhD, University of California, Berkeley, USA “for the development of a method for genome editing.” Dr. Charpentier (at right in photo) and Dr. Doudna (at left in photo) discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants, and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies, and may make the dream of curing inherited diseases come true. Researchers need to modify genes in cells if they are to find out about life’s inner workings. This used to be time-consuming, difficult, and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks. “There is enormous power in this genetic tool, which affects us all. It has not only revolutionized basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, MD, PhD, Chair of the Nobel Committee for Chemistry. As so often in science, the discovery of these genetic scissors was unexpected. During Dr. Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

October 5th

ASU’s Dr. Carl Yamashiro's Innovative Teaching Approach Gives Diagnostics Students Real-World Experience; His Outstanding Efforts Have Been Recognized by 2020 Arizona Bioscience Educator of the Year Award

Carl Yamashiro (https://chs.asu.edu/carl-yamashiro)(photos--here and at end), PhD, an Associate Clinical Professor at the College of Health Solutions at Arizona State University(ASU), has been named the 2020 Michael A. Cusanovich Arizona Bioscience Educator of the Year by the Arizona Bioindustry Association (AZ Bio) for his innovation and creativity in preparing the next generation of biomedical diagnostics professionals. In 2014, Dr. Yamashiro joined the International School of Biomedical Diagnostics, a partnership created by ASU President Michael Crow, PhD, and College of Health Solutions Professor of Practice Mara Aspinall, MBA, with Dublin City University in Ireland to offer the first Master of Science in Biomedical Diagnostics degree. This degree is designed to provide a more holistic understanding of biomedical diagnostics by joining the technology and science of diagnostics with a business and application approach. Dr. Yamashiro’s extensive experience in the diagnostics industry-- combined with his academic expertise--has been instrumental in developing an innovative degree program where students apply their diagnostics knowledge to real-world health challenges. Part of that industry-academia connection is the Applied Projects course (https://webapp4.asu.edu/catalog/course?s=BMD&n=593), the degree’s culminating experience Dr. Yamashiro created that has partnered with 40 companies, organizations, and institutions from Arizona, the U.S., and around the world to offer teams of students hands-on experience and the opportunity to build relationships with industry leaders. The students work to solve issues within these companies and organizations, putting into practice all the skills and knowledge they have gained from their biomedical diagnostics courses.

October 5th

Caltech Researcher Unveils Low-Cost Device That Detects SARS-CoV-2 Virus, Anti-Virus Antibodies, and Inflammatory Molecules in Under 10 Minutes; Device Designed for Home Use & Detects Virus in Infected, But Still Pre-Symptomatic Individuals

One feature of the COVID-19 virus that makes it so difficult to contain is that it can be easily spread to others by a person who has yet to show any signs of infection. The carrier of the virus might feel perfectly well and go about his/her daily business--taking the virus with him/her to work, to the home of a family member, or to public gatherings. A crucial part of the global effort to stem the spread of the pandemic, therefore, is the development of tests that can rapidly identify infections in people who are not yet symptomatic. Now, Caltech researchers have developed a new type of multiplexed test (a test that combines multiple kinds of data) with a low-cost sensor that may enable the at-home diagnosis of a COVID infection through rapid analysis of small volumes of saliva or blood, without the involvement of a medical professional, in less than 10 minutes. The research was conducted in the lab of Wei Gao, PhD, Assistant Professor in the Andrew and Peggy Cherng Department of Medical Engineering at Caltech. Previously, Dr. Gao and his team have previously developed wireless sensors that can monitor conditions such as gout, as well as stress levels, through the detection of extremely low levels of specific compounds in blood, saliva, or sweat. Dr. Gao's sensors are made of graphene, a sheet-like form of carbon. A plastic sheet etched with a laser generates a 3D graphene structure with tiny pores. Those pores create a large amount of surface area on the sensor, which makes it sensitive enough to detect, with high accuracy, compounds that are only present in very small amounts. In this sensor, the graphene structures are coupled with antibodies, immune system molecules that are sensitive to specific proteins, like those on the surface of a COVID virus, for example.

2020 Nobel Prize for Physiology or Medicine Awarded Jointly to Three Scientists for Discovery of Hepatitis C Virus

On October 5, 2020, it was announced that this year’s Nobel Prize in Physiology or Medicine has been awarded jointly to three scientists who have made a decisive contribution to the fight against blood-borne hepatitis, a major global health problem that causes cirrhosis and liver cancer in people around the world. Harvey J. Alter, MD, Michael Houghton, PhD, and Charles M. Rice, PhD, made seminal discoveries that led to the identification of a novel virus, Hepatitis C. Prior to their work, the discovery of the Hepatitis A and B viruses had been critical steps forward, but the majority of blood-borne hepatitis cases remained unexplained. The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives. Liver inflammation, or hepatitis, a combination of the Greek words for liver and inflammation, is mainly caused by viral infections, although alcohol abuse, environmental toxins, and autoimmune disease are also important causes. In the 1940’s, it became clear that there are two main types of infectious hepatitis. The first, named hepatitis A, is transmitted by polluted water or food and generally has little long-term impact on the patient. The second type is transmitted through blood and bodily fluids and represents a much more serious threat because it can lead to a chronic condition, with the development of cirrhosis and liver cancer. This form of hepatitis is insidious, as otherwise healthy individuals can be silently infected for many years before serious complications arise. Blood-borne hepatitis is associated with significant morbidity and mortality, and causes more than a million deaths per year world-wide, thus making it a global health concern on a scale comparable to HIV-infection and tuberculosis.

Researchers Discover Rare Genetic Form of Dementia; Mutation in VCP Gene Associated with Pathologic Buildup of Tau Proteins; Results Suggest That Restoring VCP Function Might Be Helpful in Neurological Protein Aggregation Diseases Like Alzheimer’s

A new, rare genetic form of dementia has been discovered by a team of University of Pennsylvania School of Medicine (Penn Medicine) researchers. This discovery also sheds light on a new pathway that leads to protein buildup in the brain--which causes this newly discovered disease, as well as related neurodegenerative diseases like Alzheimer's Disease--that could be targeted for new therapies. The study was published online on October 1, 2020 in Science. The article is titled “Autosomal Dominant VCP Hypomorph Mutation Impairs Disaggregation of PHF-tau.” Alzheimer's disease (AD) is a neurodegenerative disease characterized by a buildup of proteins, called tau proteins, in certain parts of the brain. Following an examination of human brain tissue samples from a deceased donor with an unknown neurodegenerative disease, researchers discovered a novel mutation in the valosin-containing protein (VCP) (image) ene in the brain, a buildup of tau proteins in areas that were degenerating, and neurons with empty holes in them, called vacuoles. The team named the newly discovered disease “vacuolar tauopathy” (VT)--a neurodegenerative disease now characterized by the accumulation of neuronal vacuoles and tau protein aggregates. "Within a cell, you have proteins coming together, and you need a process to also be able to pull them apart, because otherwise everything kind of gets gummed up and doesn't work. VCP is often involved in those cases where it finds proteins in an aggregate and pulls them apart," said Edward Lee, MD, PhD, an Assistant Professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. "We think that the mutation impairs the proteins' normal ability to break aggregates apart."

October 4th

Neural Stem Cell Exosomes Can Carry Protein Cargo Across Blood-Brain Barrier in Model System; Results Suggest Exosomes May Be Effective Vehicle for Moving Drugs from Blood into Brain

Researchers have shown that certain natural nanovesicles, namely exosomes derived from c17.2 neural stem cells (NSCs), can efficiently carry a protein cargo across an in vitro model of the blood-brain barrier (BBB) [the model BBB was made up of human brain microvascular endothelial cells (hCMEC/D3)]. This is particularly significant because drug delivery to the brain has, thus far, been greatly limited by the BBB, which tightly regulates the passage of molecules from blood to the brain and vice versa. The new results were published online on September 16, 2020 in the European Journal of Neuroscience (https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.14974). The article is titled “Heparan Sulfate Proteoglycan‐Mediated Dynamin‐Dependent Transport of Neural Stem Cell Exosomes in an In Vitro Blood–Brain Barrier Model.” The researchers showed that the exosomes are primarily taken up in brain microvascular endothelial cells via dynamin-dependent endocytosis, while heparan sulfate proteoglycans (HSPGs) on these endothelial cells act as receptors for the exosomes. The authors suggest that their data support the development of exosomes as delivery vehicles for the treatment of brain disorders via intravenous administration, obviating the need for invasive intracerebral or intracerebroventricular administration routes. Moreover, active HSPG targeting of nanoparticles, including exosomes, may be exploited for effective crossing of the BBB. The authors of the article are Bhagyashree S. Joshi (photo), PhD candidate, and her advisor Inge S. Zuhorn, PhD, Associate Professor, from the Department of Biomedical Engineering, University of Groningen, University Medical Center Groningen, The Netherlands.

[European Journal of Neuroscience article]

October 2nd

Codiak Initiates Patient Dosing in Phase 1/2 Clinical Trial of exoSTING™ Exosomes for Treatment of Solid Tumors; These Exosomes Contain Proprietary Stimulator of Interferon Genes (STING) Agonist to Activate Innate Immunity in Tumor Microenvironment

On October 1, 2020, Codiak BioSciences, Inc., a clinical-stage company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, announced the initiation of patient dosing in its Phase 1/2 clinical trial of exoSTING. exoSTING is a novel exosome therapeutic candidate engineered with the company’s engEx Platform and designed to deliver Codiak’s proprietary STING (stimulator of interferon genes) agonist specifically to tumor-resident antigen-presenting cells (APCs) to locally activate the innate immune response. The trial, which will study exoSTING in solid tumors, is Codiak’s second human clinical trial and the second clinical development program the Company has initiated in the past month. “We are enormously proud to now have both of our lead candidates in the clinic, the result of years of engineering and manufacturing innovation and a significant step forward towards fulfilling our goal of pioneering the development of engineered exosomes as a new class of medicines for diseases with high unmet medical needs,” said Douglas E. Williams, PhD, CEO, Codiak. “With exoSTING, the data from our in vitro and in vivo preclinical studies support our desired product profile, demonstrating that we can achieve targeted engagement of the STING pathway to potentially overcome the lack of cell specificity, tolerability, and limited single-agent antitumor activity associated with previous STING agonists.” exoSTING is an exosome therapeutic candidate engineered with Codiak’s engEx Platform to incorporate its proprietary STING agonist inside the lumen of the exosome, while expressing high levels of the exosomal protein, PTGFRN (prostaglandin F2 receptor inhibitor) (https://en.wikipedia.org/wiki/PTGFRN), on the surface.