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June 30th, 2020

Researchers Develop Novel Vaccine That Removes Senescent T-Cells from the Body to Improve Obesity-Induced Metabolic Disorders; “Striking Results” Obtained in Mouse Study

Aging is a multifaceted process that affects our bodies in many ways. In a new study, researchers from Osaka University in Japan developed a novel vaccine that removes aged immune cells and then demonstrated an improvement of diabetes-associated metabolic derangements by vaccinating obese mice. Aged, or senescent, cells are known to harm their surrounding younger cells by creating an inflammatory environment. A specific type of immune cell, called a T-cell (image), can accumulate in fat tissues in obese individuals in senescence, causing chronic inflammation, metabolic disorders, and heart disease. To reduce the negative effects of senescent cells on the body, senotherapy was developed to target and eliminate these rogue cells. However, as this approach does not discriminate between different types of senescent cells, it has remained unknown whether specific depletion of senescent T-cells can improve their adverse effects on organ physiology. “The idea that eliminating senescent cells improves the organ dysfunction that we experience during aging is fairly new,” says corresponding author of the study Hironori Nakagami, PhD,of the Department of Health Development and Medicine, Osaka University Graduate School of Medicine. “Because senescent T-cells can facilitate metabolic derangements similar to diabetes, we wanted to come up with a new approach to reduce the number of senescent T-cells to then reverse the negative effects they have on glucose metabolism.” To achieve their goal, the researchers developed a novel vaccine targeting the surface protein CD153 that is present on senescent T-cells populating fat tissues, thereby ensuring that normal T-cells are not affected.

American Chemical Society Names Paul Alivisatos 2021 Priestley Medalist, Society’s Highest Honor; Award Recognizes Alivisatos’ Foundational Contributions to the Chemistry of Nanoscience, Including Development of Nanocrystals As Nanotech Building Blocks

On June 30, 2020, the American Chemical Society (ACS) announced that it has selected Paul Alivisatos (photo), PhD, of the University of California (UC), Berkeley as the recipient of the 2021 Priestley Medal, the Society’s highest honor. Dr. Alivisatos (https://en.wikipedia.org/wiki/Paul_Alivisatos), the Samsung Distinguished Professor in Nanoscience and Nanotechnology Research and Professor of Chemistry and Materials Science and Engineering at the University of California (UC) Berkeley, is being recognized for “foundational contributions to the chemistry of nanoscience, development of nanocrystals as nanotechnology building blocks and leadership in the chemistry and nanoscience communities.” “Dr. Alivisatos is a true innovator in the field of nanoscience and chemistry as a whole,” says ACS CEO Thomas Connelly Jr., PhD. “His groundbreaking contributions to the fundamental physical chemistry of nanocrystals, as well as laying the foundation for the development of colloidal quantum dots, have led to significant advances in technology, medicine and renewable energy. That tremendous scientific legacy is now cemented, and I offer my heartfelt congratulations.” Dr. Alivisatos has spent the majority of his career studying nanocrystals, including their behavior and synthesis. In one of his first major breakthroughs as a pioneer in a then-emerging field, he demonstrated a method for growing quantum dots--semiconductor nanocrystals smaller than 10 nanometers--into two-dimensional shapes. This ability to create nanomaterials with precision and complexity is used by scientists and companies worldwide to create new biomedical imaging technology, high-resolution electronic displays, and energy-efficient technologies, all of which utilize quantum dots.

Particular Bacterium in Gut Microbiome Confers Resistance to Cholera; Blautia obeum Degrades Bile Salts That Normally Act As Signals for Cholera to Turn On Dormant Virulence Genes; Individuals with B. obeum in Their Gut Microbiome Are Resistant to Cholera

Many parts of the world are in the midst of a deadly pandemic of cholera, an extreme form of watery diarrhea. University of California (UC) at Riverside (UCR) scientists have discovered specific gut bacteria make some people resistant to cholera, a finding that could save lives. Cholera can kill within hours if left untreated, and it sickens as many as 4 million people a year. In a new article, published in the June 25, 2020 issue of Cell, researchers describe how gut bacteria help people resist the disease (https://www.cell.com/cell/fulltext/S0092-8674(20)30631-0) (see graphic abstract of Cell article at left and in a larger view at the bottom of this story). The article is titled “Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection.” Bacteria live everywhere on the planet--including inside the human body. UCR microbiologist Ansel Hsiao, PhD, studies whether the bacteria living in our bodies, collectively known as the human microbiome, can protect people from diseases caused by external bacteria such as Vibrio cholerae, which lives in waterways and causes cholera. Dr. Hsiao’s team examined the gut microbiomes from people in Bangladesh, where many suffer from cholera as a result of contaminated food, water, and poor sanitation infrastructure. “When people get sick, the diarrhea gets flushed into water systems that people drink from, and it’s a negative cycle,” Dr. Hsiao explained. His team wanted to determine whether prior infections or other stresses, like malnutrition, make people more vulnerable, as compared to Americans who don’t face these same pressures. The findings surprised the group, which expected stressed Bangladeshi microbiomes would allow for higher rates of infection.

Possibly Revolutionary New Treatment Alternative to Corneal Transplantation Developed in Montreal; “LiQD Cornea” Is Liquid Hydrogel That Promotes Tissue Regeneration, Thus Treating Corneal Perforations Without Need for Transplantation

A research team co-led by May Griffith (photo), PhD, a scientist at Maisonneuve-Rosemont Hospital Research Centre, which is affiliated with Université de Montréal and is part of the CIUSSS de l'Est-de-l'Île-de-Montréal, has reported results suggesting that a novel liquid hydrogel may be used to effectively treat corneal perforations and offers an alternative to corneal transplant. The results of this multinational project were published on June 17, 2020 in Science Advances. The open-access article is titled “LiQD Cornea: Pro-Regeneration Collagen Mimetics As Patches and Alternatives to Corneal Transplantation.” "Our work has led to an effective and accessible solution called LiQD Cornea to treat corneal perforations without the need for transplantation," said Dr. Griffith, who is also a full professor in the Department of Ophthalmology at Université de Montréal. "This is good news for the many patients who are unable to undergo this operation due to a severe worldwide shortage of donor corneas," she said. "Until now, patients on the waiting list have had their perforated corneas sealed with a medical-grade super glue, but this is only a short-term solution because it is often poorly tolerated in the eye, making transplantation necessary." A synthetic, biocompatible, and adhesive liquid hydrogel, LiQD Cornea, is applied as a liquid, but quickly adheres and gels within the corneal tissue. The LiQD Cornea promotes tissue regeneration, thus treating corneal perforations without the need for transplantation. Dr. Griffith praised the work of her trainees, Christopher McTiernan and Fiona Simpson, and her collaborators from around the world who have helped create a potentially revolutionary treatment to help people with vision loss avoid going blind.

June 29th

Bobwhites Listen to Each Other When Picking Habitat; University of Illinois Researchers Used Taped Calls to Lure Birds to Suitable Habitats; Hope to Increase Currently Declining Bobwhite Populations

[This article was written by Ananya Sen, a graduate student in Microbiology at the University of Illinois at Urbana-Champaign. Ms. Sen is also a science writer and her articles can be found at http://ananyasen.web.illinois.edu/. This article was originally published as a Research News article by the University of Illinois News Bureau (https://news.illinois.edu/view/6367).] Northern bobwhites are attracted to a habitat based on whether other bobwhites are present there, researchers at the University of Illinois at Urbana-Champaign report. This phenomenon, called con-specific attraction, could aid conservation efforts. Bobwhites, Colinus virginianus, are resident birds--they decide where to live and stick to that decision for the rest of their lives, said Michael Ward (https://nres.illinois.edu/directory/mpward), PhD, a Professor of Natural Resources And Environmental Sciences (https://nres.illinois.edu/), who led the research. “It’s an important decision,” he said. “It’s like sampling food at different restaurants before you decide where to eat.” The researchers played recordings of bobwhite songs to see whether they could attract the birds to unoccupied sites in the Cold Springs area of Fort Polk, Louisiana. “We played their calls on an MP3 player that was attached to a battery,” Dr. Ward said. “We tried to mimic their natural singing behavior by playing the recordings more often in the morning and less in the afternoon.” The researchers studied the sites for three years. They did not play any recordings in the first year. The next year they divided the sites into those with and without recordings. The sites were flipped the third year.

FDA Approves Merck’s KEYTRUDA® (Pembrolizumab) for First-Line Treatment of Patients with Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer, First Single-Agent, Anti-PD-1 Therapy Approved for the First-Line Treatment of These Patients

On June 29, 2020, Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA (https://en.wikipedia.org/wiki/Pembrolizumab), Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. The approval is based on results from the Phase 3 KEYNOTE-177 trial, in which KEYTRUDA significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0004]) compared with chemotherapy, the current standard of care. In the study, treatment with KEYTRUDA also more than doubled median progression-free survival (PFS) compared with chemotherapy (16.5 months [95% CI, 5.4-32.4] versus 8.2 months [95% CI, 6.1-10.2]). “Today’s approval has the potential to change the treatment paradigm for the first-line treatment of patients with MSI-H colorectal cancer, based on the important findings from KEYNOTE-177 that showed KEYTRUDA monotherapy demonstrated superior progression-free survival compared to standard of care chemotherapy,” said Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. “Our commitment to pursuing biomarker research continues to help us bring new treatments to patients, particularly for those who have few available options.” Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, and these include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT).

ReNeuron Signs Collaboration to Produce Human Neural Stem Cell (hNSC)-Derived Exosomes & to Load Them with Novel Gene-Silencing Therapeutics from Un-Named Collaborating US Biotech Company; ReNeuron Will Provide Loaded Exosomes to Collaborator

On June 25, 2020, ReNeuron Group plc (AIM: RENE), a UK-based global leader in the development of cell-based therapeutics, announced that it has signed a new research evaluation agreement with a major US biotechnology company in connection with the use of the ReNeuron’s proprietary exosomes for the delivery of novel gene-silencing therapeutics. This latest research collaboration will focus on the use of ReNeuron’s human neural stem cell (hNSC)-derived exosomes for the delivery of the US biotechnology company’s neuroscience therapeutic candidates. ReNeuron will be responsible for manufacturing exosomes and then loading them with the gene-silencing sequences after which the US biotechnology company will evaluate the loaded exosomes. Assuming positive results, the parties will jointly own the novel therapeutic candidate created for future development. The research evaluation agreement is in line with ReNeuron’s strategy of partnering its exosome technology as a novel delivery vehicle. This new agreement follows an exosome research collaboration with a major pharmaceutical company announced by ReNeuron on April 7, 2020 (http://www.reneuron.com/wp-content/uploads/RENE-Exosome-research-collabo...), reflecting the increasing level of industry interest in exosomes. ReNeuron has developed exosomes derived from hNSCs that have a natural ability to cross the blood-brain barrier and can thus be used to deliver therapeutics for diseases of the brain. The hNSC-derived exosomes can be produced through a fully-qualified, xeno-free, scalable process and the clinical-grade hNSC source cell-line ensures consistent exosome product.

37,000 Attendees Finish Up 3-Day American Association for Cancer Research (AACR) Virtual Annual MeetingII (June 22-24); All Meeting Presentations, Abstracts, and Other Materials Available Online Until September 23

[What follows is a brief report by BioQuick News Editor & Publisher Mike O’Neill on his experience virtually attending the live portion of the American Association for Cancer Research (AACR) 2020 Virtual Meeting II, with live sessions taking place July 22-24.] I just finished virtually attending much of the AACR Virtual Annual Mtg II (Mon-Wed, June 22-24). I even got in a few questions, including one on exosomes (see question at end of this note). The meeting had 37,000 registered attendees from 127 countries. Virtual attendees were rewarded with an incredible conference that included an opening day address by Nobel Prize winner Phillip Sharp and a closing day talk by a possible future Nobelist, NIH Director and former Genome Project leader Francis Collins. In his talk, Sharp mentioned that early in his career he had been recruited from Cold Spring Harbor Laboratory to MIT by Salvador Luria and David Baltimore. That put three future Nobelists in one lab. Not too bad. Collins described a number of COVID-19 efforts that are being undertaken currently by the NIH. His address from his NIH office was given in one of three COVID-19 sessions the AACR offered during this exceptional meeting. In his closing remarks, new AACR President Antoni Ribas noted that this fantastic meeting featured over 600 speakers, 125 sessions, 14 concurrent channels, and over 4,000 abstracts. All the meeting material will be available online to current and future registrants (registration is free) until September 23. Outgoing AACR President Elaine Mardis expressed her profound gratitude to everyone involved in the conference, including the major sponsor Daiichi-Sankyo, which had made it possible to offer the conference for free to registrants.

Unlike ApoE3, ApoE4 Disrupts the Neuroprotective Action of Sortilin In Neuronal Lipid Metabolism and Endocannabinoid Signaling; Results May Point to New Avenue for Development of Therapeutics for Alzheimer’s

Apolipoprotein E (ApoE) is like a delivery service for the human brain. It supplies neurons with important nutrients, including polyunsaturated fatty acids, which are building blocks of the membranes surrounding the neurons. In addition, certain unsaturated fatty acids are converted into so-called endocannabinoids. These are endogenous signaling molecules that regulate numerous functions of the nervous system, such as memory, but also the control of immune response, thereby protecting the brain from inflammation. The ApoE cargo reaches the neurons via a membrane receptor called sortilin. In a process known as endocytosis, sortilin binds ApoE and transports it into the interior of the neuron through invaginations of the cell membrane. The interaction of ApoE and sortilin has a major impact on our brain health: If not enough polyunsaturated fatty acids reach our gray cells, they begin to waste away and become susceptible to inflammatory responses. But not all ApoE is the same. There are three gene variants in humans: ApoE2, ApoE3, and ApoE4. They do not differ in their function of transporting lipids. The ability to bind to sortilin is also the same in all variants. However, people who carry the E4 variant have a twelve times greater risk of developing Alzheimer's than those with the E3 form. About 15 percent of people carry ApoE4. "Why ApoE4 significantly increases the risk of Alzheimer's is one of the central questions in Alzheimer's research," says Professor Thomas Willnow, PhD, Head of the Molecular Cardiovascular Research Lab at Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) in Germany, who for many years has been studying the development of neurodegenerative diseases.

CytoDyn and NIH of Mexico Complete Memorandum of Understanding (MOU) to Conduct Small COVID-19 Phase 3 Trial for Severe and Critically Ill Patients

On June 29, 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 today that the company and the Coordinating Commission of the National Institutes of Health and High Specialty Hospitals of Mexico (NIH) have entered into a Memorandum of Understanding (MOU) to conduct a COVID-19 clinical trial with leronlimab for severe and critically ill patients, with the potential to collaborate on additional COVID-19 trials. The NIH of Mexico is an organization that coordinates the main institutions of medical care and public research in the country. The MOU provides that CytoDyn will supply leronlimab at its expense to the NIH and both parties are proceeding forward expeditiously to complete the mutually agreed protocol for this clinical trial. Nader Pourhassan, PhD, President and Chief Executive Officer of CytoDyn, commented: “We are very pleased with the confidence demonstrated by the NIH of Mexico in our drug, leronlimab, and we are both very motivated to initiate this trial quickly to help mitigate the devastation of the COVID-19 pandemic on the citizens of Mexico. The anecdotal data received by CytoDyn (from over 70 COVID-19 critical patients who were treated under EIND in the U.S.) has impressed the NIH of Mexico and we believe with a small Phase 3 trial of only 25 patients, leronlimab could receive approval in Mexico very quickly. This Phase 3 trial is similar to our Phase 3 trial protocol in the U.S., with the exception of the number of patients.” CytoDyn has met its 75-patient enrollment target in its Phase 2 clinical trial for COVID-19, a randomized clinical trial for mild-to-moderate COVID-19 population in the U.S.