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Archive - 2021

Date

March 9th

Exosome-Mediated mRNA Delivery for SARS-CoV-2 Vaccination—Preclinical Advances Published in PrePrint by Capricor Therapeutics; Data Demonstrates Enhanced Expression & Lower Toxicity Compared to Lipid Nanoparticles; Webcast Thursday

On March 9, 2021, Capricor Therapeutics, Inc. (NASDAQ: CAPR) (https://capricor.com/), a biotechnology company focused on the development of transformative cell- and exosome-based therapeutics for the treatment and prevention of a broad spectrum of diseases, in collaboration with researchers, announced that new advances from its positive preclinical study for a multi-valent exosome-based mRNA vaccine for COVID-19 have been posted on the bioRxiv preprint server (https://www.biorxiv.org/content/10.1101/2020.11.06.371419v2) and the article been submitted for publication. The title of the preprint is “Exosome-Mediated mRNA Delivery for SARS-CoV-2 Vaccination.” “Capricor previously demonstrated that our exosome-based multivalent RNA delivery platform can induce long-lasting immune responses to multiple SARS-CoV-2 proteins, and potentially elicit a broad-based, cellular and humoral immunity. We decided to explore further the expression of RNAs with our exosome-based delivery system and compare exosomes with lipid nanoparticles specifically focused on short-term toxicity,” said Linda Marbán, PhD, CEO of Capricor. “The data demonstrated functional RNA expression in vivo, further showing the power of our exosome platform to potentially expand into areas beyond SARS-CoV-2. This strengthens my belief that our exosome platform can deliver RNA effectively into cells and drive the expression of functional proteins. The opportunities for pipeline expansion are very exciting, both in vaccines and in the delivery of therapeutic RNAs.”

March 8th

New CAR T-Cell Therapy Extends Remission in Heavily Relapsed Multiple Myeloma Patients

A new type of CAR T-cell therapy more than triples the expected length of remission for multiple myeloma patients who have relapsed several times, according to an international clinical trial with the University of Texas Southwestern (UTSW) as the lead enrolling site. Results of the trial, published in the February 25, 2021 issue of the New England Journal of Medicine, were significantly better than those seen with other therapies available to heavily relapsed and refractory myeloma patients who had already received the three main classes of treatment. Nearly three-quarters of the patients had at least a partial response to the therapy. About a third achieved a complete remission, with the disappearance of all traces of cancer. Median time without the disease worsening was 8.8 months with this new treatment, but Larry D. Anderson (photo), MD, PhD, Associate Professor of Internal Medicine and co-first author of the journal article, points out that patients who received the trial's maximum dose of engineered T-cells experienced longer remissions, bringing the average to more than 12 months. Previously, similar patients treated with currently available therapies following multiple relapses have only had an average of three to four months of remission before their disease returned. The NEJM article is titled “Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma” (https://www.nejm.org/doi/10.1056/NEJMoa2024850). "We have patients that are over two years out from their single infusion of CAR T-cells and still in remission despite having no other treatment options when they were enrolled in this trial," says Dr. Anderson, a member of the UTSW’s Harold C. Simmons Comprehensive Cancer Center who cares exclusively for patients with plasma cell disorders, mostly myeloma patients.

March 7th

MIT Study Reveals How Egg Cells (Oocytes) Get So Big—“Balloon Effect” Is Key

Egg cells are by far the largest cells produced by most organisms. In humans, they are several times larger than a typical body cell and about 10,000 times larger than sperm cells. There’s a reason why egg cells, or oocytes, are so big: They need to accumulate enough nutrients to support a growing embryo after fertilization, plus mitochondria to power all of that growth. However, biologists don’t yet understand the full picture of how egg cells become so large. A new study in fruit flies, by a team of MIT biologists and mathematicians, reveals that the process through which the oocyte grows significantly and rapidly before fertilization relies on physical phenomena analogous to the exchange of gases between balloons of different sizes. Specifically, the researchers showed that “nurse cells” surrounding the much larger oocyte dump their contents into the larger cell, just as air flows from a smaller balloon into a larger one when they are connected by small tubes in an experimental setup. “The study shows how physics and biology come together, and how nature can use physical processes to create this robust mechanism,” says Jörn Dunkel, PhD, an MIT Associate Professor of Physical Applied Mathematics. “If you want to develop as an embryo, one of the goals is to make things very reproducible, and physics provides a very robust way of achieving certain transport processes.”

Putting a Protein into Overdrive to Heal Spinal Cord Injuries--Scar-Forming Cells (NG2 Glia) Engineered to Overproduce SOX2 Protein Make New Neurons, Improving Recovery in Mouse Model

Using genetic engineering, researchers at the University of Texas Southwestern (UTSW) and Indiana University have reprogrammed scar-forming cells in mouse spinal cords to create new nerve cells, spurring recovery after spinal cord injury. The findings, published online on March 5, 2021 in Cell Stem Cell, could offer hope for the hundreds of thousands of people worldwide who suffer a spinal cord injury each year. The article is titled “In vivo Reprogramming of NG2 Glia Enables Adult Neurogenesis and Functional Recovery Following Spinal Cord Injury” (https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00059-X). Cells in some body tissues proliferate after injury, replacing dead or damaged cells as part of healing. However, explains study leader Chun-Li Zhang, (https://profiles.utsouthwestern.edu/profile/29691/chun-li-zhang.html ), PhD, Professor of Molecular Biology and a W.W. Caruth, Jr. Scholar in Biomedical Research at UTSW, the spinal cord typically does not generate new neurons after injury--a key roadblock to recovery. Because the spinal cord acts as a signal relay between the brain and the rest of the body, he adds, its inability to self-repair permanently halts communication between these two areas, leading to paralysis, loss of sensation, and sometimes life-threatening consequences such as an inability to control breathing or heart rate. Dr. Zhang notes that the brain has some limited capacity to produce new nerve cells, relying on progenitor cells to turn on distinct regenerative pathways. Using this knowledge as inspiration, he and his colleagues looked for cells that might have similar potential for regeneration in the spinal cord.

March 6th

Targeting Viral Protein (Nsp1) That Blocks Export of Host mRNA from Nucleus Could Be Therapeutic Approach to Treating COVID-19

A study that identifies how a coronavirus protein called Nsp1 blocks the activity of genes that promote viral replication provides hope for new COVID-19 treatments. Since the start of the pandemic, scientists have worked endlessly to understand SARS-CoV-2, the coronavirus that causes COVID-19. Even with the arrival of vaccines, the virus is still spreading and there is a need to develop alternative therapies. Scientists hope to achieve this by studying how SARS-CoV-2 infects cells and propagates itself while avoiding the body’s natural immune system. Now, researchers at the University of Texas Southwestern (UTSW) have contributed to unravelling this puzzle with their results published in the February 5, 2021 issue of Science Advances. The open-access article is titled “Nsp1 Protein of SARS-CoV-2 Disrupts the mRNA Export Machinery to Inhibit Host Gene Expression” (https://advances.sciencemag.org/content/7/6/eabe7386). “When a virus infects a cell, the way the host cell reacts is to alter cellular pathways (or networks) in certain ways to counteract the viral infection. Viruses can target many of these pathways to favor their own replication,” says Beatriz Fontoura (photo), PhD, Professor of Cell Biology at UTSW and corresponding author of the paper. Viruses replicate by suppressing the host cell’s genes in favor of their own. One way they do this is by blocking the export of messenger RNA (mRNA) from the nucleus of the cell to another compartment called the cytoplasm. Some of these mRNAs code for proteins that can only be made by the cell in the cytoplasm. So, by blocking their export from the nucleus, viruses prevent some proteins from being made (e.g., antiviral proteins) and simultaneously free up the cell’s machinery for their own replication.

Researchers Use Machine Learning to Identify Nine Biomarkers for Autism Spectrum Disorder (ASD) in Blood; Findings May Permit Earlier Diagnosis and Treatment

Using machine-learning tools to analyze hundreds of proteins, University of Texas Southwestern (UTSW) researchers have identified a group of nine biomarkers in blood that could lead to an earlier diagnosis of children with autism spectrum disorder (ASD) and, in turn, more effective therapies sooner. The identification of nine serum proteins whose levels strongly predict ASD was reported in a study published online on February 24, 2021 by PLOS ONE. The open-access article is titled “Blood Biomarker Discovery for Autism Spectrum Disorder: A Proteomic Analysis” (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246581). Earlier diagnosis, followed by prompt therapeutic support and intervention, could have a significant impact on the 1 in 59 children diagnosed with autism in the United States. Being able to identify children on the autism spectrum when they are toddlers could make a big difference, says Dwight German, PhD, Professor of Psychiatry at UTSW and senior author of the study. Currently, the average age of a child diagnosed with ASD in the U.S. is 4 years old. Diagnosis before the age of 4 means that a child is more likely to get effective, evidence-based treatment, such as therapies directed at core ASD symptoms, including inflexible behaviors and the lack of communication or social skills. Many blood-based biomarker candidates have been investigated, including neurotransmitters, cytokines, and markers of mitochondrial dysfunction, oxidative stress, and impaired methylation. However, given the prevalence of ASD, the use of machine learning to incorporate demographic and clinical data into the analysis could more powerfully examine disease status and symptom severity.

Exosome-Based Urinary Test May Provide Non-Invasive Early Diagnosis of Human Kidney Transplant Rejection; Analysis Reveals Rejection Signature of 15 mRNAs in Urinary Exosomes; Approach May Enable Earlier, More Effective Treatment

Patients can spend up to six years waiting for a kidney transplant. Even when they do receive a transplant, up to 20 percent of patients will experience rejection. Transplant rejection occurs when a recipient's immune cells recognize the newly received kidney as a foreign organ and refuse to accept the donor's antigens. Current methods for testing for kidney rejection include invasive biopsy procedures, causing patients to stay in the hospital for multiple days. A study by investigators from Exosome Diagnostics (https://www.exosomedx.com/) and Brigham and Women's Hospital proposes a new, noninvasive way to test for transplant rejection using exosomes--tiny vesicles that can contain mRNA--from urine samples. Their findings were published online on March 2, 2021 in the Journal of the American Society of Nephrology. The open-access article Is titled “Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection” (https://jasn.asnjournals.org/content/early/2021/03/03/ASN.2020060850). "Our goal is to develop better tools to monitor patients without performing unnecessary biopsies. We try to detect rejection early, so we can treat it before scarring develops," said Jamil Azzi (photo), MD, Associate Physician in the Division of Renal Transplant at the Brigham and an Associate Professor of Medicine at Harvard Medical School. "If rejection is not treated, it can lead to scarring and complete kidney failure. Because of these problems, recipients can face life-long challenges." Before this study, physicians ordered biopsies or blood tests when they suspected that a transplant recipient was rejecting the donor organ. Biopsy procedures pose risks of complications, and 70-80 percent of biopsies end up being normal.

Monoclonal Antibodies Against Glucagon-Producing Alpha Cells in Pancreas Convert These Cells to Insulin-Producing Beta Cells in Animal Models; Approach May Lead to Treatment for Both Type 1 and Type 2 Diabetes

Blocking cell receptors for glucagon, the counter-hormone to insulin, cured mouse models of diabetes by converting glucagon-producing cells into insulin producers instead, a team led by University of Texas (UT) Southwestern (UTSW) researchers reports in a new study. The findings, published online on March 2, 2021 in PNAS, could offer a new way to treat both Type 1 and Type 2 diabetes in people. The open-access article is titled “Glucagon Blockade Restores Functional β-cell Mass in Type 1 Diabetic Mice and Enhances Function of Human Islets.” More than 34 million Americans have diabetes, a disease characterized by a loss of beta cells in the pancreas. Beta cells produce insulin, a hormone necessary for cells to absorb and use glucose, a type of sugar that circulates in the blood and serves as cellular fuel. In Type 2 diabetes, the body’s tissues develop insulin resistance, prompting beta cells to die from exhaustion from secreting excess insulin to allow cells to take in glucose. In Type 1 diabetes, which affects about 10 percent of the diabetic population, beta cells die from an autoimmune attack. Both kinds of diabetes lead to severely elevated blood sugar levels that eventually can cause a host of possible complications, including loss of limbs and eyesight, kidney damage, diabetic coma, and death. Most treatments for diabetes focus on insulin, but its counterpart--the hormone glucagon that is produced by alpha cells in the pancreas--has received comparatively little attention, says study leader May-Yun Wang (photo) (https://profiles.utsouthwestern.edu/profile/17718/may-yun-wang.html), PhD, Assistant Professor of Internal Medicine at UTSW. Glucagon binds to receptors on cells in the liver, prompting this organ to secrete glucose.

March 5th

CytoDyn’s Phase 3 Trial of Leronlimab (Vyrologix™) Demonstrates 24% Reduction in Mortality and Faster Hospital Discharge for Mechanically Ventilated Critically Ill COVID-19 Patients; Webcast Monday

On March 05, 2021, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing Vyrologix™ (leronlimab-PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, reported that the Phase 3 trial of leronlimab for the treatment of severe-to-critical patients with COVID-19 demonstrated continued safety, substantial improvement in survival rate, and faster hospital discharge in critically ill COVID-19 patients. The trial’s data has been reported to the U.S. Food and Drug Administration (FDA), the U.K.’s Medicines & Healthcare product Regulatory Agency (MHRA) and Health Canada (HC), and the company is in discussions with each to determine the best path forward for approval of leronlimab for treatment of COVID-19 in critically ill populations. A manuscript of the trial’s data is being prepared and will be submitted for publication in one or more major medical journals. Highlights from the trial’s data for this critically ill population include the following:
--Survival Benefit: There was a 24% reduction in all-cause mortality (primary endpoint of the study) in the leronlimab arm versus the placebo arm of the study.
--Shortened Time to Recovery: The average length of hospital stay was reduced by 6 days for patients who received leronlimab with "commonly used COVID-19 treatments,” also referred to as “Standard of Care” or “SoC,” compared to placebo patients who received SoC only, with a statistically significant p-value of 0.005.
--Discharged Alive: In addition, patients who received leronlimab demonstrated an improved probability of "discharged alive" at Day 28 (28% versus 11%), a 166% better rate than in the placebo group.

Advance In “Optical Tweezers” May Boost Biomedical Research

Much like the Jedis in Star Wars use “the force” to control objects from a distance, scientists can use light or “optical force” to move very small particles. The inventors of this ground-breaking laser technology, known as “optical tweezers,” were awarded the 2018 Nobel Prize in Physics. Optical tweezers are used in biology, medicine, and materials science to assemble and manipulate nanoparticles such as gold atoms. However, the technology relies on a difference in the refractive properties of the trapped particle and the surrounding environment. Now scientists have discovered a new technique that allows them to manipulate particles that have the same refractive properties as the background environment, overcoming a fundamental technical challenge. The study “Optical Tweezers Beyond Refractive Index Mismatch Using Highly Doped Upconversion Nanoparticles” was published online on February 18, 2021 in Nature Nanotechnology (https://www.nature.com/articles/s41565-021-00852-0). "This breakthrough has huge potential, particularly in fields such as medicine," says leading co-author Dr. Fan Wang from the University of Technology Sydney (UTS). "The ability to push, pull, and measure the forces of microscopic objects inside cells, such as strands of DNA or intracellular enzymes, could lead to advances in understanding and treating many different diseases such as diabetes or cancer. Traditional mechanical micro-probes used to manipulate cells are invasive, and the positioning resolution is low. They can only measure things like the stiffness of a cell membrane, not the force of molecular motor proteins inside a cell," he says. The research team developed a unique method to control the refractive properties and luminescence of nanoparticles by doping nanocrystals with rare-earth metal ions.