VPS39

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones. More Data on Underlying Conditions and COVID-19 Severity A study out of RCSI University of Medicine and Health Sciences and the HSE Health Protection Surveillance Centre (HPSC) in Ireland has further defined the association between comorbidities and poor outcomes with COVID-19. The study took place between March and July 2020 and collected national data in Ireland from both hospital and community settings. It collected data for almost 20,000 confirmed cases of COVID-19. The results were published in The Lancet Regional Health – Europe. Of the patients studied, there were 1,476 deaths, 2,811 hospitalizations, and 438 ICU admissions. The conditions that carried the most risk were chronic heart disease, a chronic neurological condition, chronic kidney disease and cancer. Morbid obesity was also identified as being associated with severe outcomes. “Previous studies conducted have suggested that specific underlying conditions influence adverse health outcomes among those with a confirmed diagnosis of COVID-19,” said Kathleen Bennett, associate professor in Biostatistics, RCSI. “However, the majority of these studies have focused on hospital-based or local populations only. This study is the first population-based research to capture data across all settings in Ireland, including both community and hospital settings and so it gives us a better picture of the impact of the disease on patients at the population level.” Gilead’s Remdesivir Plus Hep C Drugs Effective Against COVID-19 Researchers with Mount Sinai Hospital and Mount Sinai School of Medicine tested a combination of Gilead’s remdesivir, an antiviral drug, with repurposed drugs for hepatitis C virus (HCV). The combinations, they found, were 10-times more effective at inhibiting SARS-CoV-2, the virus behind COVID-19. Four HCV drugs in combination with remdesivir improved the efficacy of remdesivir. They were simeprevir, vaniprevir, paritaprevir, and grazoprevir. The research group tested 10 HCV drugs, some already approved by the U.S. Food and Drug Administration (FDA). They utilized a supercomputer to model how drugs bind to viral proteins and predicted that those 10 would bind tightly to the SARS-CoV-2 Main protease (Mpro). They also found that seven of the drugs inhibited the SARS-CoV-2 protease. They then tested the seven drugs in monkey and human cells in culture. Four of the HCV drugs inhibited a different SARS-CoV-2 protease called PLpro. It was the four drugs that targeted PLpro that increased the efficacy of remdesivir by as much as 10-fold. While remdesivir must be dosed intravenously, the four HCV drugs are oral. Type 2 Diabetes Associated with Muscle Gene Researchers at Lund University found that in type 2 diabetes, a specific gene related to muscle cells is less active than it is in other people. The gene, VPS39, is important for when muscle cells absorb sugar from blood and build new muscle. In type 2 diabetes, the body’s ability to generate insulin is impaired, resulting in chronically increased blood sugar. The muscles are generally worse at absorbing sugar from food, and this muscle function and strength are typically impaired in type 2 diabetic patients. Their study, which was on muscle stem cells in type 2 diabetes patients compared to healthy controls, found that there were more than twice as many epigenetic changes in the type 2 diabetes group during the differentiation from muscle stem cell to mature muscle cells. Muscle-specific genes were not regulated normally, and epigenetics did not appear to function in the same way in cells from people with type 2 diabetes did. How Brain Cells in Alzheimer’s Patients Lose Their Identity Investigators with the Salk Institute grew neurons that resemble better than ever before the brain cells in older patients. It appears to have given them insight into how the brain cells go off-track in Alzheimer’s patients, losing their cellular identity. The brain cells were characterized by markers of stress in addition to changes where the cells become less specialized. This is similar to what has been observed in cancer cells. The researchers collected skin cells from 13 sporadic, age-related Alzheimer’s patients, as well as cells from three people with the rarer, inherited form of Alzheimer’s. Their controls were skin cells from 19 people age-matched but without Alzheimer’s. Using fibroblasts, they induced neurons, then compared the molecular differences in the cells. They found that the cells from people with Alzheimer’s had specific characteristics different from the healthy control cells. The Alzheimer’s cells lacked synaptic structures, which are vital to sending signals to each other. There were also changes in signaling pathways, which control cell function, an indication the cells were under stress. They also found that the induced Alzheimer’s neurons had similar molecular signatures to immature nerve cells found in the developing brain. What this was interpreted to mean was the Alzheimer’s-based cells had lost their mature identity. A New Anti-Aging Compound Scientists at Washington University School of Medicine found a natural compound, nicotinamide mononucleotide (NMN), that in earlier studies seemed to counteract aging and improved metabolic health in mice, also had positive clinical effects in people. They conducted a clinical trial of postmenopausal women with prediabetes. They demonstrated that NMN improved the ability of insulin to increase glucose uptake in skeletal muscle. This ability is often abnormal in obese, prediabetic or type 2 diabetics. NMN improved expression of genes involved in muscle structure are remodeling. However, it did not lower blood sugar levels, blood pressure, improve blood lipids, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as was observed in mice. “Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study,” said Samuel Klein, senior investigator and the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. “Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvement in other markers of metabolic health, which we did not detect in our study participants.”