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.
Studies in cell and animal models reveal insights into cancer cells’ vulnerability that could lead to new strategies against brain cancers
Researchers have devised a new plan of attack against a group of deadly childhood brain cancers collectively called diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), thalamic glioma and spinal cord glioma. Scientists at the National Institutes of Health, Stanford University, California, and Dana-Farber Cancer Institute, Boston, identified a drug pair that worked together to both kill cancer cells and counter the effects of a genetic mutation that causes the diseases.
The researchers showed that combining the two drugs – panobinostat and marizomib – was more effective than either drug by itself in killing DMG patient cells grown in the laboratory and in animal models. Their studies also uncovered a previously unrecognized vulnerability in the cancer cells that scientists may be able to exploit to develop new strategies against the cancer and related diseases. The results were published Nov. 20 in Science Translational Medicine.
DIPG is a rare, deadly childhood brain cancer. Here, a confocal micrograph shows DIPG cells, grown from patient cells, in culture.
Safety data analyzed from five NIH inpatient clinical trials
National Institutes of Health researchers found that a single, low-dose ketamine infusion was relatively free of side effects for patients with treatment-resistant depression. Elia Acevedo-Diaz, M.D., Carlos Zarate, M.D., and colleagues at the NIH’s National Institute of Mental Health (NIMH) report their findings in the Journal of Affective Disorders.
Studies have shown that a single, subanesthetic-dose (a lower dose than would cause anesthesia) ketamine infusion can often rapidly relieve depressive symptoms within hours in people who have not responded to conventional antidepressants, which typically take weeks or months to work. However, widespread off-label use of intravenous subanesthetic-dose ketamine for treatment-resistant depression has raised concerns about side effects, especially given its history as a drug of abuse.
“The most common short-term side effect was feeling strange or loopy,” said Acevedo-Diaz, of the Section on the Neurobiology and Treatment of Mood Disorders, part of the NIMH Intramural Research Program (IRP) in Bethesda, Maryland. “Most side effects peaked within an hour of ketamine administration and were gone within two hours. We did not see any serious, drug-related adverse events or increased ketamine cravings with a single-administration.”
Technique key to scale up manufacturing of therapies from induced pluripotent stem cells
Researchers used artificial intelligence (AI) to evaluate stem cell-derived “patches” of retinal pigment epithelium (RPE) tissue for implanting into the eyes of patients with age-related macular degeneration (AMD), a leading cause of blindness.
The proof-of-principle study helps pave the way for AI-based quality control of therapeutic cells and tissues. The method was developed by researchers at the National Eye Institute (NEI) and the National Institute of Standards and Technology (NIST) and is described in a report appearing online today in the Journal of Clinical Investigation. NEI is part of the National Institutes of Health.
“This AI-based method of validating stem cell-derived tissues is a significant improvement over conventional assays, which are low-yield, expensive, and require a trained user,” said Kapil Bharti, Ph.D., a senior investigator in the NEI Ocular and Stem Cell Translational Research Section.
“Our approach will help scale up manufacturing and will speed delivery of tissues to the clinic,” added Bharti, who led the research along with Carl Simon Jr., Ph.D., and Peter Bajcsy, Ph.D., of NIST.
Scanning electron micrograph showing iPS cell-derived RPE tissue (gray) cultured on a fiber-based scaffold (blue).
Exceptional early stage scientists mark NIH’s commitment to build the next generation of biomedical researchers
The National Institutes of Health has selected five scientists as Lasker Clinical Research Scholars, part of a joint initiative with the Albert and Mary Lasker Foundation, to continue building a pipeline of exemplary clinical scientists. This highly competitive program provides talented, early stage researchers the opportunity to carry out independent clinical and translational research for five to seven years at NIH. The researchers also have the possibility of additional years of financial support, at NIH or an NIH-funded research institution, upon project review. The new researchers join 23 Lasker Scholars hired since 2012.
“The addition of these five creative minds to the Lasker Clinical Research Scholars program builds upon a remarkable foundation of clinician-scientists who will lead the NIH in producing innovative biomedical discoveries,” said NIH Director Francis S. Collins, M.D., Ph.D.
Lasker Scholars have access to the NIH Clinical Center, the largest hospital in the world devoted to clinical research. The Lasker Foundation will provide additional developmental support to the scholars while they are working at NIH by funding travel to scientific meetings and providing the opportunity to participate in selected foundation activities, including the Lasker Award ceremonies.
Investigators at the National Institutes of Health have found that sesame allergy is common among children with other food allergies, occurring in an estimated 17% of this population. In addition, the scientists have found that sesame antibody testing — whose utility has been controversial — accurately predicts whether a child with food allergy is allergic to sesame. The research was published on Oct. 28 in the journal Pediatric Allergy and Immunology.
“It has been a challenge for clinicians and parents to determine if a child is truly allergic to sesame,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “Given how frequently sesame allergy occurs among children who are allergic to other foods, it is important to use caution to the extent possible when exposing these children to sesame.”
Sesame is among the 10 most common childhood food allergies. Only an estimated 20% to 30% of children with sesame allergy outgrow it. Severe reactions to sesame are common among sesame-allergic children. About 1.1 million people in the United States, or an estimated 0.23% of the U.S. population, have sesame allergy, according to a recently published study funded by NIAID. These factors underscore the need to optimize recognition and diagnosis of this allergy. The Food and Drug Administration is currently considering whether to include sesame in the list of allergens that must be disclosed on food labels.
Scientists hope findings mean vaccine supplies could stretch farther
A single dose of a highly diluted VSV-Ebola virus (EBOV) vaccine — approximately one-millionth of what is in the vaccine being used to help control the ongoing Ebola outbreak in the Democratic Republic of the Congo (DRC) — remains fully protective against disease in experimentally infected monkeys, according to National Institutes of Health scientists. The NIH investigators completed the vaccine dosage study using cynomolgus macaques and an updated vaccine component to match the EBOV Makona strain that circulated in West Africa from 2014-16. The study appears in Lancet’s EBioMedicine.
Nearly 250,000 people have received the investigational VSV-EBOV vaccine since August 2018 as part of a “ring vaccination” program to help stem the outbreak. The vaccine appears to be safe and highly effective. The manufacturer has announced that it has submitted a biologics license application to the U.S. Food and Drug Administration. VSV-EBOV is based on a live-attenuated vesicular stomatitis virus and delivers an EBOV protein to elicit protective immune responses. With the continued need to vaccinate individuals in the DRC and surrounding countries, a potential shortage of VSV-EBOV vaccine is a concern and further dose adjustment is a possible solution.
Scientists from NIH’s Rocky Mountain Laboratories (RML), part of the National Institute of Allergy and Infectious Diseases, tested several dosage strengths, including one with 10 million plaque-forming units (PFU). They determined that a vaccine with 10 PFUs was just as effective as the highest dose tested (a dose which was still lower than the one currently in use in the DRC). They vaccinated macaques 28 days prior to infecting them with a lethal dose of EBOV and then monitored the animals for 42 days after infection. Even the macaques given the lowest dose appeared completely protected from disease due to EBOV.
Samples of cerebrospinal fluid used to detect tauopathies
National Institutes of Health scientists have developed an ultrasensitive new test to detect abnormal forms of the protein tau associated with uncommon types of neurodegenerative diseases called tauopathies. As they describe in Acta Neuropathologica, this advance gives them hope of using cerebrospinal fluid, or CSF — an accessible patient sample — to diagnose these and perhaps other, more common neurological diseases, such as Alzheimer’s disease.
Scientists have linked the abnormal deposition of tau in the brain to at least 25 different neurodegenerative diseases. However, to accurately diagnose these diseases, brain tissue often must be analyzed after the patient has died.
For their study, the researchers used the same test concept they developed when using post-mortem brain tissue samples to detect the abnormal tau types associated with Pick disease, Alzheimer’s disease and chronic traumatic encephalopathy (CTE). They adapted the test to use CSF for the detection of abnormal tau of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and other less common tauopathies.
Representative negative-stained transmission electron microscopy images of 4R RT-QuIC products seeded with brain homogenates from individuals with the designated diseases –frontotemporal dementia and Parkinsonism linked to chromosome 17; corticobasal degeneration; and progressive supranuclear palsy.
Tesamorelin prevented progression to liver fibrosis in NIH study
Researchers at the National Institutes of Health and their colleagues at Massachusetts General Hospital (MGH) in Boston report that the injectable hormone tesamorelin reduces liver fat and prevents liver fibrosis (scarring) in people living with HIV. The study was conducted by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute, both parts of NIH. The findings were published online today in The Lancet HIV.
“Many people living with HIV have overcome significant obstacles to live longer, healthier lives, though many still experience liver disease,” said NIAID Director Anthony S. Fauci, M.D. “It is encouraging that tesamorelin, a drug already approved to treat other complications of HIV, may be effective in addressing non-alcoholic fatty liver disease.”
Non-alcoholic fatty liver disease, or NAFLD, frequently occurs alongside HIV, affecting as many as 25% of people living with HIV in the developed world. However, no effective treatments currently exist to treat the condition, which is a risk factor for progressive liver disease and liver cancer. Investigators led by Colleen M. Hadigan, M.D., senior research physician in NIAID’s Laboratory of Immunoregulation, and Steven K. Grinspoon, M.D., Chief of the Metabolism Unit at MGH, tested whether tesamorelin could decrease liver fat in men and women living with both HIV and NAFLD. Among the participants enrolled, 43% had at least mild fibrosis, and 33% met the diagnostic criteria for a more severe subset of NAFLD called nonalcoholic steatohepatitis (NASH). Thirty-one participants were randomized to receive daily 2-mg injections of tesamorelin, and 30 were randomized to receive identical-looking injections containing a placebo. Researchers provided nutritional counseling to all participants, as well as training in self-administering the daily injections. Researchers then compared measures of liver health in both groups at baseline and 12 months.
A microscopic image of liver tissue affected by non-alcoholic fatty liver disease (NAFLD). The large and small white spots are excess fat droplets filling liver cells (hepatocytes).
Research explores dual role of amygdala in regulating pain
A new study in mice uncovered a previously unknown role that the central amygdala can play in upgrading or downgrading pain signals in the brain’s circuitry. The study, published in Cell Reports, was conducted by researchers at the Division of Intramural Research at the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health.
"We know that pain is not static and that it can be modulated by several factors. Early research showed that the central amygdala, long known for its role in processing fear, can dial up pain signals. Yet, other studies have pointed to the central amygdala’s role in suppressing pain, or prompting an analgesic response,” said Yarimar Carrasquillo, Ph.D., senior author of the study and lead scientist for the Behavioral Neurocircuitry and Cellular Plasticity Section in the NCCIH Intramural Division. “This study unravels what seemed to be a contradiction in early research and reveals a previously hidden ‘switch’ in the central amygdala that can turn up or turn down pain signals.”
The “switch” acts more like a “pain rheostat,” similar to a home thermostat that modulates temperature — the pain rheostat reacts to pain signals to modulate pain sensations. In the mice, researchers found that activity in neurons that express protein kinase C-delta (CeA-PKCδ) turned up the pain rheostat and demonstrated an increase in pain-related responses. Conversely, researchers found that activity in neurons that express somatostatin (CeA-Som) turned down the pain rheostat, inhibiting nociception or the chain of activity in the nerves required to communicate pain.
Nerve-Injury-Induced ERK Activation and c-Fos Expression Is Preferentially Localized to CeA-PKCδ Neurons.
NIH study examines effects of blood vessel damage following brain injury
Using advanced imaging, researchers have uncovered new information regarding traumatic microbleeds, which appear as small, dark lesions on MRI scans after head injury but are typically too small to be detected on CT scans. The findings published in Brain suggest that traumatic microbleeds are a form of injury to brain blood vessels and may predict worse outcomes. The study was conducted in part by scientists at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“Traumatic microbleeds may represent injury to blood vessels that occur following even minor head injury,” said Lawrence Latour, Ph.D., NINDS researcher and senior author of the study. “While we know that damage to brain cells can be devastating, the exact impact of this vascular injury following head trauma is uncertain and requires further study.”
This study, which involved researchers from Cold Spring Harbor Laboratory in New York and the Uniformed Services University of the Health Sciences in Bethesda, Maryland, included 439 adults who experienced head injury and were treated in the emergency department. The subjects underwent MRI scans within 48 hours of injury, and again during four subsequent visits. Participants also completed behavioral and outcome questionnaires.
The results showed that 31% of all study participants had evidence of microbleeds on their brain scans. More than half (58%) of participants with severe head injury showed microbleeds as did 27% of mild cases. The microbleeds appeared as either linear streaks or dotted, also referred to as punctate, lesions. The majority of patients who exhibited microbleeds had both types. The findings also revealed that the frontal lobes were the brain region most likely to show microbleeds.
Traumatic microbleeds appear as dark lesions on MRI scans and suggest damage to brain blood vessels after head injury.
