Friday, October 23, 2020
The plant compound apigenin improved the cognitive and memory deficits usually seen in a mouse model of Down syndrome, according to a study by researchers at the National Institutes of Health and other institutions. Apigenin is found in chamomile flowers, parsley, celery, peppermint and citrus fruits. The researchers fed the compound to pregnant mice carrying fetuses with Down syndrome characteristics and then to the animals after they were born and as they matured. The findings raise the possibility that a treatment to lessen the cognitive deficits seen in Down syndrome could one day be offered to pregnant women whose fetuses have been diagnosed with Down syndrome through prenatal testing. The study appears in the American Journal of Human Genetics.
Down syndrome is a set of symptoms resulting from an extra copy or piece of chromosome 21. The intellectual and developmental disabilities accompanying the condition are believed to result from decreased brain growth caused by increased inflammation in the fetal brain. Apigenin is not known to have any toxic effects, and previous studies have indicated that it is an antioxidant that reduces inflammation. Unlike many compounds, it is absorbed through the placenta and the blood brain barrier, the cellular layer that prevents potentially harmful substances from entering the brain. Compared to mice with Down symptoms whose mothers were not fed apigenin, those exposed to the compound showed improvements in tests of developmental milestones and had improvements in spatial and olfactory memory. Tests of gene activity and protein levels showed the apigenin-treated mice had less inflammation and increased blood vessel and nervous system growth.
Monday, October 19, 2020
In a National Institutes of Health-funded study involving both mice and patients who are part of an NIH Clinical Center trial, researchers discovered that a gene, called PIEZO2, may be responsible for the powerful urge to urinate that we normally feel several times a day. The results, published in Nature, suggest that the gene helps at least two different types of cells in the body sense when our bladders are full and need to be emptied. These results also expand the growing list of newly discovered senses under the gene’s control.
Urine is produced when the kidneys extract waste and excess water from the blood and send it to the bladder. Over time, it fills up and expands like a balloon, putting tension on the bladder muscles. Then, at a certain point, the body senses that it is reaching a limit, which triggers the urge to urinate.
The PIEZO2 gene contains instructions for making proteins that are activated when cells are stretched or squeezed. In this study, the researchers found that patients who are born with a genetic deficiency in PIEZO2 have trouble sensing bladder filling while experiments in mice suggested the gene plays two critical roles in this process. It may help certain bladder cells gauge expansion while also sparking neurons to relay tension signals to the rest of the nervous system.
Researchers discovered that a gene called PIEZO2 may help us sense when our bladders are full, and it is time to urinate. Above is an example of a mouse bladder used in the study.
Tuesday, October 13, 2020
As genome-editing trials become more common, informed consent is changing
As public interest and expanded research in human genome editing grows, many questions remain about ethical, legal and social implications of the technology. People who are seriously ill may overestimate the benefits of early clinical trials while underestimating the risks. This makes properly understanding informed consent, the full knowledge of risks and benefits of treatments, especially important.
In response to this emerging need, researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, asked patients, parents and physicians in the sickle cell disease community what they wanted and needed to know about genome editing to make informed decisions about participating in genome-editing clinical trials. Gene-editing treatments, which appear to provide a potential for sickle cell, are among the most widely publicized medical advances in recent years. The results were published this week in the journal AJOB Empirical Bioethics.
“An important goal of informed consent is to facilitate decisions that are consistent with a person’s values,” said Sara Hull, Ph.D., director of the Bioethics Core at NHGRI. “By talking to sickle cell disease stakeholders ahead of time, we can learn more about their values and hopefully do a better job of pinpointing what kinds of information will be most useful to potential research participants as they make very a difficult decision.”
Monday, October 5, 2020
Results suggest retrieval of cellular powerplants via an energy feedback loop sustains communication
Our thoughts, feelings, and movements are controlled by billions of neurons talking to each other at trillions of specialized communication points called synapses. In an in-depth study of neurons grown in laboratory petri dishes, National Institutes of Health researchers discovered how the chattiest of some synapses find the energy to support intense conversations thought to underlie learning and memory. Their results, published in Nature Metabolism, suggest that a series of chemical reactions control a feedback loop that senses the need for more energy and replenishes it by recruiting cellular powerplants, called mitochondria, to the synapses. The experiments were performed by researchers in a lab led by Zu-Hang Sheng, Ph.D., at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).
The team studied synapses that use the neurotransmitter glutamate to communicate. Communication happens when a packet of glutamate is released from presynaptic boutons which are tiny protrusions that stick out, like beads on a string, of long, wiry parts of neurons called axons. Previously, Dr. Sheng’s team showed that synaptic communication is an energy-demanding process and that mitochondria traveling along axons can control signals sent by boutons. Boutons that had mitochondria sent stronger and more consistent signals than those that were missing powerplants. The difference was due to higher energy levels produced by the mitochondria in the form of ATP.
In this study, led by Sunan Li, Ph.D., a post-doctoral fellow at NINDS, the team investigated what happens when boutons undergo intense communication thought to underlie learning and memory. They found that this type of signaling quickly dropped energy levels at boutons. These changes triggered a series of chemical reactions controlled by an energy sensor called AMP-activated protein kinases (AMPK) that ultimately led to the rapid recruitment of mitochondria to the boutons. Genetically blocking or chemically interfering with this feedback loop prevented the delivery of mitochondria to boutons and lowered energy levels. This, in turn, reduced synaptic responses during intense communication more than seen in control cells and slowed the recovery of the responses after the bursts ended. The researchers concluded that this feedback loop may normally play a critical role in providing the energy needed to sustain synaptic communication throughout a healthy nervous system. For example, they cite studies which implied that problems with this system may occur in some cases of Alzheimer’s disease and other neurological disorders.
Intense neural conversations thought to underlie learning and memory may be fueled by an energy-sensing feedback loop. Scientist monitored energy levels in the form of ATP as neurons talked to each other.
Monday, October 5, 2020
National Institutes of Health intramural researcher Harvey J. Alter, M.D., has won the 2020 Nobel Prize in Physiology or Medicine for his contributions to the discovery of the hepatitis C virus. Dr. Alter is a Senior Scholar at the NIH Clinical Center’s Department of Transfusion Medicine and shares the award with Michael Houghton, Ph.D., University of Alberta, Canada, and Charles M. Rice, Ph.D., Rockefeller University, New York City.
The Royal Swedish Academy of Sciences said, “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.”
“I am overwhelmed at the moment, but so pleased that this originally obscure virus has proven to have such a large global impact,” said Dr. Alter. “There are so many persons at NIH who advanced my research, but for now I can only thank NIH, itself, for creating the permissive and collaborative environment that supported these studies over the course of decades. I don’t believe my contributions could have occurred anywhere else.”
Dr. Harvey J. Alter
Tuesday, September 29, 2020
A Phase 1 trial of an investigational mRNA vaccine to prevent SARS-CoV-2 infection has shown that the vaccine is well-tolerated and generates a strong immune response in older adults. A report published today in the New England Journal of Medicine describes the findings from the study, which was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. SARS-CoV-2 is the virus that causes COVID-19 disease.
The experimental vaccine, mRNA-1273, was co-developed by researchers at NIAID and Moderna, Inc. of Cambridge, Massachusetts. The Phase 1 trial began on March 16, 2020, and was expanded to enroll older adults about one month later. Older adults are more vulnerable to complications of COVID-19 and are an important population for vaccination. Understanding how the vaccine affects older adults is a critical part of measuring its safety and efficacy.
The trial was conducted at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle, Emory University in Atlanta, and NIAID’s Vaccine Research Center (VRC) clinic at the NIH Clinical Center in Bethesda, Maryland. Julie Ledgerwood, D.O., deputy director and chief medical officer at the VRC, oversaw the study at the NIH site. The Coalition for Epidemic Preparedness Innovations (CEPI) supported the manufacturing of the vaccine candidate for this trial. This trial is supported by the Infectious Diseases Clinical Research Consortium (IDCRC) through NIAID.
Colorized scanning electron micrograph of an apoptotic cell (gray) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample.
Thursday, September 24, 2020
New findings by scientists at the National Institutes of Health and their collaborators help explain why some people with COVID-19 develop severe disease. The findings also may provide the first molecular explanation for why more men than women die from COVID-19.
The researchers found that more than 10% of people who develop severe COVID-19 have misguided antibodies―autoantibodies―that attack the immune system rather than the virus that causes the disease. Another 3.5% or more of people who develop severe COVID-19 carry a specific kind of genetic mutation that impacts immunity. Consequently, both groups lack effective immune responses that depend on type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses. Whether these proteins have been neutralized by autoantibodies or―because of a faulty gene―were produced in insufficient amounts or induced an inadequate antiviral response, their absence appears to be a commonality among a subgroup of people who suffer from life-threatening COVID-19 pneumonia.
These findings are the first published results from the COVID Human Genetic Effort, an international project spanning more than 50 genetic sequencing hubs and hundreds of hospitals. The effort is co-led by Helen Su, M.D., Ph.D., a senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH; and Jean-Laurent Casanova, M.D., Ph.D., head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University in New York. Major contributions were made by Luigi Notarangelo, M.D., chief of the NIAID Laboratory of Clinical Immunology and Microbiology (LCIM); Steven Holland, M.D., director of the NIAID Division of Intramural Research and senior investigator in the NIAID LCIM; clinicians and investigators in hospitals in the Italian cities of Brescia, Monza and Pavia, which were heavily hit by COVID-19; and researchers at the Uniformed Services University of the Health Sciences in Bethesda, Maryland.
Colorized scanning electron micrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample.
Monday, September 21, 2020
First publication from NIH ME/CFS study takes deep dive into key feature of the disease
One of the major symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM), the worsening of symptoms after physical or mental activities. Using their own words and experiences, people with ME/CFS described how debilitating PEM can be in a study in Frontiers in Neurology. This is the first publication to come out of the National Institutes of Health’s intramural post-infectious ME/CFS study.
“Post-exertional malaise following normal activities is unique to ME/CFS and we do not understand the biology underlying this severe and harmful feature of the disease,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “In-depth conversations with people who experienced post-exertional malaise and listening to them describe their individual experiences can provide a perspective not achieved through surveys. This study provides a window into just how much post-exertional malaise can affect a person’s quality of life.”
Researchers led by Avindra Nath, M.D., clinical director of NINDS, recruited 43 individuals with ME/CFS to participate in nine focus groups discussing their experiences with post-exertional malaise, including activities that led to it, how long it lasted, and techniques they used to help decrease their symptoms. Five out of the nine focus groups included participants who experienced PEM following a cardiopulmonary exercise test (CPET), which can measure how the body reacts to exercise and is often conducted using a stationary bike.
Monday, September 14, 2020
A National Institutes of Health-funded study found that people with substance use disorders (SUDs) are more susceptible to COVID-19 and its complications. The research, published today in Molecular Psychiatry, was co-authored by Nora D. Volkow, M.D., director of the National Institute on Drug Abuse (NIDA). The findings suggest that health care providers should closely monitor patients with SUDs and develop action plans to help shield them from infection and severe outcomes.
By analyzing the non-identifiable electronic health records (EHR) of millions of patients in the United States, the team of investigators revealed that while individuals with an SUD constituted 10.3% of the total study population, they represented 15.6% of the COVID-19 cases. The analysis revealed that those with a recent SUD diagnosis on record were more likely than those without to develop COVID-19, an effect that was strongest for opioid use disorder, followed by tobacco use disorder. Individuals with an SUD diagnosis were also more likely to experience worse COVID-19 outcomes (hospitalization, death), than people without an SUD.
“The lungs and cardiovascular system are often compromised in people with SUD, which may partially explain their heightened susceptibility to COVID-19,” said Dr. Volkow. “Another contributing factor is the marginalization of people with addiction, which makes it harder for them to access health care services. It is incumbent upon clinicians to meet the unique challenges of caring for this vulnerable population, just as they would any other high-risk group.”
Colorized scanning electron micrograph of an apoptotic cell (blue) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample.
Wednesday, September 9, 2020
NIH observational study suggests that the drug may decrease risk of pneumonia and death in this population
The drug miglustat appears to stabilize the swallowing problems that occur in children and adolescents with Niemann-Pick type C1 (NPC1), a rare and ultimately fatal neurological disease, according to a study by researchers at the National Institutes of Health. The authors conclude that the drug could slow the deterioration of swallowing function in NPC1 cases and decrease the risk of pneumonia resulting from aspiration, or inhaling food or drink. Aspiration pneumonia accounts for roughly 2 out of 3 deaths in people with NPC1.
The study was conducted by Forbes D. Porter, M.D., Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development and colleague in the NIH Clinical Center. It appears in the JAMA Neurology.
NPC1 is a rare genetic disorder that causes a progressive decline in neurological and cognitive functions. Although miglustat is not approved by the Food and Drug Administration to treat NPC1, the drug is thought to stabilize the neurological deterioration seen in the disease and is frequently prescribed to treat it. Previous studies have suggested that by slowing this neurological deterioration, miglustat can stabilize swallowing ability. However, these studies have not documented any specific swallowing improvements for patients.