Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:
BETHESDA, Md. (AP) — Sam Srisatta, a 20-year-old Florida college student, spent a month living inside a government hospital here last fall, playing video games and allowing scientists to document every morsel of food that went into his mouth.
From big bowls of salad to platters of meatballs and spaghetti sauce, Srisatta noshed his way through a nutrition study aimed at understanding the health effects of ultraprocessed foods, the controversial fare that now accounts for more than 70% of the U.S. food supply. He allowed The Associated Press to tag along for a day.
“Today my lunch was chicken nuggets, some chips, some ketchup,” said Srisatta, one of three dozen participants paid $5,000 each to devote 28 days of their lives to science. “It was pretty fulfilling.”
Examining exactly what made those nuggets so satisfying is the goal of the widely anticipated research led by National Institutes of Health nutrition researcher Kevin Hall.
“What we hope to do is figure out what those mechanisms are so that we can better understand that process,” Hall said.
New inoculation based on Ebola VSV vaccine concept
A National Institutes of Health research group with extensive experience studying ebolavirus countermeasures has successfully developed a vaccine against Sudan virus (SUDV) based on the licensed Ebola virus (EBOV) vaccine. SUDV, identified in 1976, is one of the four viruses known to cause human Ebolavirus disease. The new vaccine, VSV-SUDV, completely protected cynomolgus macaques against a lethal SUDV challenge. The findings were published in the journal The Lancet Microbe.
SUDV is distinct from and less common than EBOV, but similarly deadly. A recent four-month SUDV outbreak in Uganda that ended on Jan. 11, 2023, caused 142 confirmed cases and 55 deaths. No treatment or vaccine for SUDV disease is licensed, although candidates are in clinical and preclinical trials. One of these candidates is VSV-SUDV, developed and tested by scientists at NIH’s National Institute of Allergy and Infectious Diseases in Hamilton, Montana.
The live-attenuated vaccine uses genetically engineered vesicular stomatitis virus (VSV), an animal virus that primarily affects cattle, to express a SUDV protein as a single-dose vaccine. The researchers developed VSV-SUDV using techniques that led to Ervebo, the VSV-EBOV vaccine that the European Medicines Agency and the U.S. Food and Drug Administration approved in 2019 as the first vaccine for the prevention of Ebola virus disease. In the current studies, the investigators replaced the key EBOV protein in Ervebo with the comparable protein from SUDV.
Colorized scanning electron micrograph of filamentous Ebola virus particles (green) attached to and budding from a chronically infected VERO E6 cell (blue).
New research offers clues about the biology of cells in the spinal cord that die off in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. A team of researchers supported by the National Institutes of Health found evidence linking motor neurons’ large cell size and supporting structure with the genes that underlie their vulnerability to degeneration in ALS. Findings appeared in Neuron.
The study resulted in a catalog or 'atlas' characterizing the diverse community of cell types within the human spinal cord. By examining gene expression at the single-cell level, the researchers identified dozens of cell types in the spinal cord and analyzed their molecular profiles. They demonstrated the usefulness of the atlas by looking closely at motor neurons, which provide voluntary movement and motor control. Motor neurons, which degenerate and die in ALS, are large cells with one long extension called an axon ― up to a meter long ― that conducts signals from the spinal cord to the muscle fiber.
The team found that motor neurons are distinguished by a set of genes that may enable the large size of the motor neuron cell body and lengthy axon, but also underlie their vulnerability to degeneration. Their molecular profile was defined by genes involved in cytoskeletal structure, which gives the cell shape and organizes the structures within; neurofilament genes related to cell size; and genes linked to the onset of ALS. Additional experiments showed that ALS-related genes are also enriched in motor neurons in mice. Taken together, the study gives insight into ALS and demonstrates the utility of the spinal cell atlas to study disease and possible interventions.
A newly published paper in The Lancet shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small, first-in-human clinical trial. The vaccine, developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, could someday be an important tool to respond to Marburg virus outbreaks.
This first-in-human, Phase 1 study tested an experimental MARV vaccine candidate, known as cAd3-Marburg, which was developed at NIAID’s Vaccine Research Center (VRC). This vaccine uses a modified chimpanzee adenovirus called cAd3, which can no longer replicate or infect cells, and displays a glycoprotein found on the surface of MARV to induce immune responses against the virus. The cAd3 vaccine platform demonstrated a good safety profile in prior clinical trials when used in investigational Ebola virus and Sudan virus vaccines developed by the VRC.
Colorized scanning electron micrograph of Marburg virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (orange).
NIH-wide resource will champion diversity, equity, inclusion and accessibility
The National Institute of Biomedical Imaging and Bioengineering (NIBIB) has established the Center for Biomedical Engineering Technology Acceleration (BETA Center), a new intramural research program to solve a range of medicine’s most pressing problems. The BETA Center will serve the wider NIH intramural research program as a biotechnology resource and catalyst for NIH research discoveries.
The center will incorporate a focused engineering approach to accelerate the development, validation and dissemination of cutting-edge technologies. Areas of emphasis will include biomedical imaging, biosensing, engineered and synthetic biology, nanomaterials and biomaterials, artificial intelligence, modeling, computation and informatics. A unique feature of the center will be its ability to rapidly assemble expert teams for purpose-driven technology development to address urgent national and global health needs.
“The BETA Center will be a catalyst for innovation and collaboration,” said NIBIB Director Bruce J. Tromberg, Ph.D. “Engineering and technology development are central to everything that NIH does. New tech drives new biomedical discoveries, and new discoveries are transformed into cutting-edge methods, devices and knowledge that can be widely disseminated.”
A fundamental objective of the BETA Center is to expand diversity, equity, inclusion and accessibility (DEIA) at NIBIB, building on the inherent interdisciplinary nature of biomedical engineering.
Large NIH-supported study showed that rural-dwelling Black men are at greatest risk
Adults living in rural areas of the United States have a 19% higher risk of developing heart failure compared to their urban counterparts, and Black men living in rural areas have an especially higher risk — 34%, according to a large observational study supported by the National Institutes of Health.
The study, one of the first to look at the link between living in rural America and first-time cases of heart failure, underscores the importance of developing more customized approaches to heart failure prevention among rural residents, particularly Black men. The study was largely funded by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, and the findings, produced in collaboration with Vanderbilt University Medical Center, Nashville, Tennessee, publish today in JAMA Cardiology.
“We did not expect to find a difference of this magnitude in heart failure among rural communities compared to urban communities, especially among rural-dwelling Black men,” said Véronique L. Roger, M.D., M.P.H., the study’s corresponding author and a senior investigator with the Epidemiology and Community Health Branch in NHLBI’s Division of Intramural Research. “This study makes it clear that we need tools or interventions specifically designed to prevent heart failure in rural populations, particularly among Black men living in these areas.”
Study co-author Sarah Turecamo, a fourth-year medical student at New York University Grossman School of Medicine, New York City, and part of the NIH Medical Research Scholars Program, agreed. “It is much easier to prevent heart failure than to reduce its mortality once you have it,” Turecamo said.
The proportion of opioid overdose deaths involving buprenorphine, a medication used to treat opioid use disorder, did not increase in the months after prescribing flexibilities were put in place during the COVID-19 pandemic, according to a new study. These data provide evidence that may help to inform buprenorphine prescribing policies. Published today in JAMA Network Open,this study was a collaborative effort between researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the Centers for Disease Control and Prevention (CDC).
These data are consistent with a recent study reporting that COVID-era expansion of methadone access for the treatment of opioid use disorder was not associated with an increase in methadone-involved overdose deaths.
In 2021, nearly 107,000 people died of a drug overdose, with 75 percent of those deaths involving an opioid. The overall rise in overdose deaths is largely attributable to the proliferation in the drug supply of illicit fentanyl, a highly potent synthetic opioid. Though the benefits of providing medication for opioid use disorder are well-known, only 22 percent of people with opioid use disorder receive medications. Buprenorphine, one of these medications, helps reduce opioid misuse, decrease risk for injection-related infectious diseases, and decrease risk for fatal and non-fatal overdoses.
“Research has shown beyond a doubt that medications for opioid use disorder are overwhelmingly beneficial and can be lifesaving, yet they continue to be vastly underused,” said NIDA Director and senior author, Nora Volkow, M.D. “Expanding more equitable access to these medications for people with substance use disorders is a critical part of our nation’s response to the overdose crisis. The findings from this study strengthen existing evidence suggesting that greater flexibility in prescribing may be one safe method for working toward this goal.”
NIH study provides new insights on role of gut in staph colonization
A promising approach to control Staphylococcus aureus bacterial colonization in people — using a probiotic instead of antibiotics — was safe and highly effective in a Phase 2 clinical trial. The new study, reported in The Lancet Microbe, found that the probiotic Bacillus subtilis markedly reduced S. aureus colonization in trial participants without harming the gut microbiota, which includes bacteria that can benefit people. The research was conducted by researchers at the National Institutes of Health led by Michael Otto, Ph.D., an NIH senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID).
Methicillin-resistant S. aureus, or MRSA, is familiar to many people as a cause of serious disease. Less well known is that S. aureus often lives in the nose, on the body and in the gut without causing any harm. However, if the skin barrier is broken, or the immune system compromised, these colonizing bacteria can cause serious skin, bone, lung, and blood infections.
The prevention of S. aureus infections using approaches to 'decolonize' the body has gained increased attention as the spread of antibiotic resistance limits treatment options. Some decolonization strategies are controversial because they also require large amounts of antibiotics, raising concerns about damage to the microbiota and the development of antibiotic resistance. So far, it appears that only nasal S. aureus colonization can be targeted with topical antibiotics without doing too much harm, but bacteria quickly can recolonize in the nose from the gut.
MRSA (yellow) being ingested by neutrophil (purplish blue).
NIH study shows genotype-first approach uncovers new links to genetic conditions
National Institutes of Health researchers have published an assessment of 13 studies that took a genotype-first approach to patient care. This approach contrasts with the typical phenotype-first approach to clinical research, which starts with clinical findings. A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms; this finding uncovered new relationships between genes and clinical conditions, broadened the traits and symptoms associated with known disorders, and offered insights into newly described disorders. The study was published in the American Journal of Human Genetics.
“We demonstrated that genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention,” says Caralynn Wilczewski, Ph.D., a genetic counselor at the National Human Genome Research Institute’s (NHGRI) Reverse Phenotyping Core and first author of the paper.
Typically, to treat genetic conditions, researchers first identify patients who are experiencing symptoms, then they look for variants in the patients’ genomes that might explain those findings. However, this can lead to bias because the researchers are studying clinical findings based on their understanding of the disorder. The phenotype-first approach limits researchers from understanding the full spectrum of symptoms of the disorders and the associated genomic variants.
“Genomics has the potential to change reactive medicine into preventative medicine,” said Leslie Biesecker, M.D., NIH distinguished investigator, director of NHGRI’s Center for Precision Health Research and a senior author of the article. “Studying how taking a genotype-first approach to research can help us learn how to model predictive and precision medicine in the future.”
NIH findings may provide early clues about increased risks for advanced biological aging and premature death
Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine.
Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels — which go up when fluid intake goes down — and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age.
“The results suggest that proper hydration may slow down aging and prolong a disease-free life,” said Natalia Dmitrieva, Ph.D., a study author and researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.
A clinical trial led by the National Cancer Institute (NCI), part of the National Institutes of Health, has resulted in the first approval of a treatment for advanced alveolar soft part sarcoma (ASPS). The immunotherapy drug atezolizumab (Tecentriq) was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children 2 years and older with ASPS that has spread to other parts of the body or cannot be removed by surgery.
ASPS is an extremely rare cancer that affects mostly adolescents and young adults. The approval was based on data from a non-randomized phase 2 trial funded by NCI and led by Dr. Alice Chen, M.D., of the Developmental Therapeutics Clinic in NCI’s Division of Cancer Treatment and Diagnosis (DCTD). Genentech, a member of the Roche Group and the manufacturer of atezolizumab, provided the drug to NCI through a cooperative research and development agreement. The results of the study are being prepared for publication.
“Forty percent of the patients were treated at the NIH Clinical Center in Bethesda," said James H. Doroshow, M.D., director of DCTD. “Our ability to bring patients in from all over the world was a key factor in the ability to do the study.”
“This approval will make a huge impact in terms of a rare disease that has been particularly challenging to treat,” Dr. Chen noted.
Left frame: Normally, tumor cells (purple) evade the immune system’s T cells (pink) by expressing a checkpoint protein known as PD-L1. Right frame: Atezolizumab (Tecentriq) binds to PD-L1 and blocks it from binding to another checkpoint protein, PD-1. This helps T cells regain their ability to kill tumor cells.
