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April 19th, 2020

First COVID-19 Patient Treated with Inhaled Nitric Oxide Therapy; Prior Studies Have Shown NO May Prevent Viral Replication, Improve Arterial Oxygenation, Reduce Need for Ventilation Support, & Prevent Proliferation of Lung Infiltrates

On March 30, 2020, Bellerophon Therapeutics, Inc. (Nasdaq: BLPH), a clinical-stage biotherapeutics company focused on developing treatments for cardiopulmonary diseases, announced that emergency expanded access treatment with its INOpulse(R) inhaled nitric oxide (iNO) system (iNO) was initiated for the first time in a patient with a diagnosis of the novel coronavirus disease COVID-19 at the University of Miami School of Medicine. The treatment follows the recent decision by the U.S. Food and Drug Administration (FDA) to grant emergency expanded access that allows INOpulse to be used immediately for the treatment of COVID-19 under the care and supervision of the patient’s physician. "Based on previous studies that demonstrate the benefits of iNO in oxygenation and immune response, INOpulse has the potential to be used as a viable treatment option for COVID-19," said the treating physician, Roger Alvarez, DO, MPH, Assistant Professor, University of Miami School of Medicine. "The cardiopulmonary benefit demonstrated by INOpulse in various indications provides the potential to prevent deterioration in patients with COVID-19, allowing ventilators to be preserved for the most critically ill. INOpulse's ease of administration could significantly decrease the burden on therapists and nurses as they combat this pandemic with constrained resources." NO is a molecule naturally produced in the endothelial lining of blood vessels that plays a significant role in vasodilation, or opening of the arteries, including arteries in the lung.

April 19th

Rockefeller University Launches Broad Range of Studies on COVID-19

Rockefeller University experts in infectious disease, immunology, biochemistry, structural biology, and genetics have begun over a dozen projects in recent weeks aimed at better understanding the biology of the SARS-CoV-2 virus, which is responsible for the current global COVID-19 pandemic. The research, which involves 18 laboratories and over 130 scientists, has the goal of discovering or developing new, urgently needed approaches to prevent and treat the disease. Although most Rockefeller laboratories have ceased on-campus operations to reduce the spread of the illness, exceptions have been made for those researchers working on essential COVID-19-related projects. Because the development, scale-up, and deployment of a safe and effective vaccine for the virus are still well over the horizon, the researchers are focusing on parallel approaches to provide alternative means of prevention and therapy, attacking the problem from many angles. Projects include the development of antibodies and other protein therapeutics capable of preventing or treating the infection; development of small molecules that inhibit the activity of viral or human proteins that are required for viral replication; improved animal models for testing potential treatments; and identification of new vulnerabilities of the virus via both genomic studies of humans with unusual sensitivity or resistance to infection, and cell-based screens using CRISPR gene-editing technology. “These projects directly relate to pathophysiology, prevention, and treatment of COVID-19, as well as the basic biology of the SARS-CoV-2 virus itself,” says Richard P. Lifton, MD, PhD, the university’s president.

MIT Scientists Design Water-Soluble, Modified Cytokine Receptors That Can Bind Cytokines; New Molecules May Prove Useful in Treating “Cytokine Storms” Associated with COVID-19 and Other Infections

One of the defining features of Covid-19 is the excessive immune response that can occur in severe cases. This burst of immune over-reaction, also called a cytokine storm, damages the lungs and can be fatal. A team of MIT researchers has developed specialized proteins, similar in structure to antibodies, that they believe could soak up these excess cytokines. “The idea is that they can be injected into the body and bind to the excessive cytokines as generated by the cytokine storm, removing the excessive cytokines and alleviating the symptoms from the infection,” says Rui Qing, PhD, an MIT research scientist who is one of the senior authors of the study. The researchers have reported their initial findings in Quarterly Review of Biophysics (QRB) Discovery, and they now hope to begin testing their proteins in human cells and in animal models of cytokine release and coronavirus infection. The article is titled “QTY Code-Designed Water-Soluble Fc-Fusion Cytokine Receptors Bind to Their Respective Ligands.” Shuguang Zhang, PhD, a principal research scientist in the MIT Media Lab’s Laboratory of Molecular Architecture, is also a senior author of the paper. Shilei Hao, PhD, a visiting scientist at MIT, is the lead author of the study, and David Jin, MD, PhD, CEO and President of Avalon GloboCare, is also an author. The researchers’ work on blocking cytokine storms grew out of a project that Dr. Zhang began ten years ago to develop modified versions of membrane-embedded proteins. These proteins are usually difficult to study because once they are extracted from the cell membrane, they only maintain their structure if they are suspended in special types of detergents. After working on the problem for several years, Dr. Zhang and Dr.

Princeton Researchers Design Shorter Promoters for Gene Delivery of Larger or Multiple Genes in Gene Therapy for Neurological Diseases; New Promoters Can Keep Transferred Genes Active for Long Periods of Time

A recently developed system for switching on the activity of genes could improve treatments for a broad range of neurological diseases. Esteban Engel, PhD, a researcher in viral neuroengineering in the Princeton Neuroscience Institute at Princeton University and Director of the Institute’s Viral Core Facility, and his team have developed new gene promoters, which act like switches to turn on gene expression, that promise to broaden the ability to deliver large genes and keep them active for long periods of time. The research was published online on April 14, 2020 in Molecular Therapy: Methods & Clinical Development. The open-access article is titled “Small Alphaherpesvirus Latency-Associated Promoters Drive Efficient and Long-Term Transgene Expression in the Central Nervous System.” [Please see video describing this work in press release at (https://www.eurekalert.org/pub_releases/2020-04/pu-nta041720.php)]. The team is developing these genetic switches for use in gene therapy, the practice of delivering new genes to replace or assist ones that are faulty. Gene therapy is a promising strategy for many diseases, including disorders that involve the brain, such as Parkinson's disease and Alzheimer's disease. To carry genes into cells, scientists take advantage of the fact that viruses come equipped with the machinery to gain entry to cells. Over the years, scientists have engineered viruses to deliver genes in ways that are safe and don't cause disease. One of the viruses commonly used for this is the relatively harmless adeno-associated virus (AAV). Dr. Engel and his team created new gene promoters that turn on genes after they have been transported into neurons, the cells of the brain and nervous system.

April 18th

ReNeuron Announces Exosome Research Collaboration; Agrees to Produce Exosomes for the Delivery of Gene-Silencing Sequences

On April 7, 2020, ReNeuron Group plc (AIM: RENE), a UK-based global leader in the development of cell-based therapeutics, announced that it has signed a research agreement with an unnamed major pharmaceutical company to explore the potential use of the Company's proprietary exosomes to deliver novel therapeutics. The agreement follows the Company's strategy of collaborating with pharmaceutical and biotechnology companies to use its exosome technology as a novel delivery vehicle. ReNeuron's exosomes are derived from its CTX neural stem cell line and have the ability to cross the blood brain barrier and to be manufactured at scale. The research collaboration will focus on the use of the Company's exosomes for the delivery of gene silencing sequences created by the pharmaceutical company. ReNeuron will be responsible for manufacturing exosomes and then loading them with the gene silencing sequences after which the pharmaceutical company will evaluate the loaded exosomes. ReNeuron will be paid by the pharmaceutical company for manufacturing and loading the exosomes in the initial phase of the collaboration. This is ReNeuron's second research collaboration following the signing of an ongoing agreement with a U.S. pharmaceutical company in January 2019. "We are delighted to have signed this latest exosome research collaboration agreement with an experienced leader in the discovery and development of novel gene silencing-based therapeutics," commented Olav Hellebø, MBA, Chief Executive Officer of ReNeuron.

Capricor Initiates Compassionate Use Program for Severe COVID-19 Patients Using CAP-1002, Its Novel Cell Therapy Based on Cardiosphere-Derived Cells; CDCs Release Exosomes That May Mitigate Severe Inflammatory Response Associated with COVID-19

On April 3, 2020, Capricor Therapeutics (NASDAQ: CAPR) a clinical-stage biotechnology company focused on the development of first-in-class biological therapeutics for the treatment or prevention of serious diseases, announced it is providing CAP-1002, its novel cell therapy to patients with advanced COVID-19 under the compassionate use pathway. Two patients were treated in the previous week at a leading healthcare center in Los Angeles, California with additional patients planned in the coming weeks. Infusions of CAP-1002 were administered safely and patients are currently clinically stable. “Physicians leading the fight against COVID-19 patients approached Capricor to discuss the use of CAP-1002 due to its strong immunomodulatory capabilities. They believe that the use of CAP-1002 for the treatment or attenuation of ARDS (acute respiratory distress syndrome) pneumonia in COVID-19 patients is based on solid scientific rationale and pre-clinical data. We know from previously published pre-clinical data that CAP-1002 mitigates the release of anti-inflammatory cytokines, as well as macrophage activation in a number of models of inflammation, including sepsis and autoimmune diseases. It is believed that COVID-19-induced ARDS pneumonia is a response to an exaggerated and sustained cytokine storm. As such, we are hopeful that CAP-1002 will be of value to patients with respect to the treatment of COVID-19,” said Linda Marbán, PhD, Capricor’s President and Chief Executive Officer. The compassionate use act allows the FDA to immediately collect information on experimental treatments and then make the appropriate decisions about the safety and efficacy of those treatments.

Orgenesis & Excella-Bio Announce Breakthrough Manufacturing Process for Bioxomes™ (Proprietary Synthetic Exosomes/Extracellular Vesicles); Patented Process Results in Uniform, Scalable Production & Ability to Deliver Specific Cargo to Targeted Cells

On March 31, 2020, Orgenesis Inc. (NASDAQ: ORGS) (“Orgenesis” or the “Company”), a pioneering, global biotech company committed to lowering costs, accelerating commercialization, and transforming the delivery of cell and gene therapies (CGTs), announced that it has developed a breakthrough and patented manufacturing process for Bioxomes™ (synthetic exosomes/extracellular vesicles), through its collaboration and licensing agreement with Excella-Bio Ltd. Exosomes, or extracellular vesicles (EVs), are small vesicles that can transfer DNA, RNA, and proteins from the cell of origin to other, often targeted cells, thereby enabling alteration of the function of the targeted cells. It is belieed that exosomes can provide the same therapeutic benefit of whole cells, without the risks and difficulties of administering entire cells to patients. Together, Orgenesis and Excella-Bio have developed Bioxomes, which are synthetic exosomes/EVs. Until now, exosome/EV production has been based on conventional ultracentrifugation or ultrafiltration. These are both complex and costly techniques. Bioxomes are engineered and produced through a patented method as membrane nanoparticles isolated from cell cultures of various sources. Orgenesis and ExcellaBio have now demonstrated the optimization and scale-up of Bioxomes™, while generating consistent and repeatable results, including uniform particles sizes. These Bioxomes have demonstrated the ability to fuse with cell membranes and deliver an intracellular cargo, in a similar manner to that of natural exosomes. Bioxomes can be sourced effectively from various cell cultures. These include mesenchymal stem cells, immortalized cells, immune cells, and epithelial cells.

Mysterious Tuft Cells Found to Play Role in Pancreatitis

Persistent inflammation of the pancreas (chronic pancreatitis) is a known risk factor for developing pancreatic cancer, the third-deadliest cancer in the United States. Tuft cells (cells sensitive to chemical (chemosensory) changes typically found in the intestines and respiratory tract) had previously been discovered in the pancreas, but their function has largely remained a mystery. Now, a team of Salk Institute scientists, led by Professor Geoffrey Wahl, PhD, and Staff Scientist Kathleen DelGiorno, PhD, has uncovered the formation of tuft cells during pancreatitis and the surprising role of tuft cells in immunity, using mouse models of pancreatitis. The findings, published online in Frontiers in Physiology on February 14, 2020, could lead to the development of new biomarkers to test for pancreatitis and pancreatic cancer. The open-access article is titled “Tuft Cell Formation Reflects Epithelial Plasticity in Pancreatic Injury: Implications for Modeling Human Pancreatitis.” "By understanding these early stages of pancreas disease, we hope our work will lead to the development of new strategies to diagnose and treat pancreatitis and pancreatic cancer early on," says Dr. Wahl, co-corresponding author and holder of the Daniel and Martina Lewis Chair in Salk's Gene Expression Laboratory. The pancreas is an abdominal organ that plays a role in digestion and blood sugar regulation. Yet, scientists know little about how the pancreas recovers from injuries, such as pancreatitis, or fights off pancreatic cancer. Most of the pancreas is composed of acinar cells, which produce and secrete digestive enzymes. Acinar cells also have the ability to transform into another type of cell called a tuft cell.

Male Ring-Tailed Lemurs Exude Fruity-Smelling Odorants from Their Wrists to Attract Mates

In an article published online in Current Biology on April 16, 2020, scientists reported that male ring-tailed lemurs (Lemur catta) become more attractive to females by secreting a fruity and floral aroma from their wrists. Using detailed chemical analysis, the researchers identified three compounds responsible for this sweet scent, marking the first time that pheromones have been identified in a primate. The open-access article is titled “Key Male Glandular Odorants Attracting Female Ring-Tailed Lemurs.” "During the yearly breeding season, male lemurs rub the glands on their wrists against their fluffy tails and then wave them at females in a behavior called 'stink flirting,'" says senior author Kazushige Touhara, PhD, Professor and biochemist at the University of Tokyo. Ring-tailed lemurs have well-developed scent glands on their shoulders and wrists. These glands are typically used to designate social rank, territory, and reproductive status. However, behavioral observations show they also use their scent glands to catch the attention of females. "Because only ring-tailed lemurs have these wrist glands and exhibit 'stink flirting' behavior, we reasoned that specific odorants for sexual communication must be involved," Dr. Touhara says. At the Japanese Monkey Center (JMC) in Aichi and The Research Institute of Evolutionary Biology in Tokyo, Japan, Dr. Touhara and his team tracked the behavior of a conspiracy of ring-tailed lemurs. They observed that female lemurs sniffed the scent markings left by males more often and for longer periods of time during the breeding season--when females are sexually receptive.

April 17th

Individual Genetic Variation in Immune System Genes (HLA) May Affect Differences in Severity of COVID-19 Infection and Susceptibility

Genetic variability in the human immune system may affect susceptibility to, and severity of infection by, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease (COVID-19). The research was published online on April 17, 2020 in the Journal of Virology, a publication of the American Society for Microbiology. The open-access article is titled “Human Leukocyte Antigen Susceptibility Map for SARS-CoV-2.” Individual genetic variation may explain differences in the strength of immune responses. Certain immune system genes, called human leukocyte antigen (HLA) genes that are involved in recognizing pathogens, vary from person to person. Variations can influence how well the immune system recognizes a given pathogen. Poor recognition of SARS-CoV-2 could cause a person to be more vulnerable to the virus. "In particular, understanding how variation in HLA [a component of the immune system containing multiple genes] may affect the course of COVID-19 could help identify individuals at higher risk from the disease," according to the authors of the new study, who are from Oregon Health & Science University, Portland, Oregon, and the Portland VA Research Foundation. The first author is PhD candidate Austin Nguyen, and the senior author is Reid F. Thompson, MD, PhD, both from the Oregon Health & Science University. The authors show that individual HLA, haplotype, and full genotype variability likely influence the capacity to respond to SARS-CoV-2 infection, and note that certain alleles in particular could be associated with more severe infection, as has previously been shown with SARS-CoV (the SARS virus).