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.
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.
IRP mouse study could prompt scientists to rethink how benzodiazepines work
Between 1999 and 2017, the United States experienced a 10-fold increase in the number of people who died from overdoses of Valium and other benzodiazepines. For years, scientists thought that these powerful sedatives, which are used to treat anxiety, muscle spasms, and sleeping disorders, worked alone to calm nerves. Now, in an article published in Science, researchers from the National Institutes of Health show that this view of the drugs and the neural circuits they affect may have to change. In a study of mice, scientists discovered that both may need the assistance of a ‘sticky’ gene, named after a mythological figure, called Shisa7.
“We found that Shisa7 plays a critical role in the regulation of inhibitory neural circuits and the sedative effects some benzodiazepines have on circuit activity,” said Wei Lu, Ph.D., a Stadtman Investigator at NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We hope the results will help researchers design more effective treatments for a variety of neurological and neuropsychiatric disorders that are caused by problems with these circuits.”
Dr. Lu’s lab studies the genes and molecules used to control synapses; the trillions of communications points made between neurons throughout the nervous system. In this study, his team worked with researchers led by Chris J. McBain, Ph.D., senior investigator at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), to look at synapses that rely on the neurotransmitter gamma-aminobutyric acid (GABA) to calm nerves. Communication at these synapses happens when one neuron fires off packets of GABA molecules that are then quickly detected by proteins called GABA type A (GABAA) receptors on neighboring neurons.
In a study of mice, NIH researchers showed that a protein encoded by a gene called Shisa7 (green) may boost the nerve calming effects of valium and other benzodiazepines by sticking to GABA type A neurotransmitter receptors (red).
Strategy appears feasible for decontaminating hunting, meat processing equipment
A 5-minute soak in a 40% solution of household bleach decontaminated stainless steel wires coated with chronic wasting disease (CWD) prions, according to a new study by National Institutes of Health scientists. The scientists used the wires to model knives and saws that hunters and meat processors use when handling deer, elk and moose — all of which are susceptible to CWD. The research was conducted at Rocky Mountain Laboratories (RML) in Hamilton, Montana. RML is a component of the NIH’s National Institute of Allergy and Infectious Diseases. The findings are published in the open-access journal PLOS One.
CWD is a brain-damaging and fatal prion disease in cervids, members of the deer family. To date CWD has never been found in people. However, other prion diseases can affect people, therefore scientists, wildlife managers and public health agencies have suggested handling CWD cervid tissues with caution. CWD is spreading in North America, increasing the potential for human exposure. The disease has been found in cervids in 26 states and three Canadian provinces, as well as in Norway, Finland and South Korea. Not all animals infected with CWD will show signs of disease, but those that do appear weak and thin.
Infectious prions — types of proteins found in mammals that when misfolded can cause disease — are extremely difficult to inactivate, which led the scientists to seek a practical, low-cost CWD decontamination method. Bleach has been proven as a decontaminant against other types of prions but had never been tested against CWD.
‘Forward-oriented’ design might boost treatment effectiveness and broaden use
Researchers at the National Institutes of Health have developed a new and improved viral vector — a virus-based vehicle that delivers therapeutic genes — for use in gene therapy for sickle cell disease. In advanced lab tests using animal models, the new vector was up to 10 times more efficient at incorporating corrective genes into bone marrow stem cells than the conventional vectors currently used, and it had a carrying capacity of up to six times higher, the researchers report.
The development of the vector could make gene therapy for sickle cell disease much more effective and pave the way for wider use of it as a curative approach for the painful, life-threatening blood disorder. Sickle cell disease affects about 100,000 people in the United States and millions worldwide.
“Our new vector is an important breakthrough in the field of gene therapy for sickle cell disease,” said study senior author John Tisdale, M.D., chief of the Cellular and Molecular Therapeutic Branch at the National Heart, Lung, and Blood Institute (NHLBI). “It’s the new kid on the block and represents a substantial improvement in our ability to produce high capacity, high efficiency vectors for treating this devastating disorder.”
Diagram shows steps involved in conducting gene therapy for sickle cell disease.
A new study published this week online in Emerging Infectious Diseases suggests that transmission of a protozoan parasite from insects may also cause leishmaniasis-like symptoms in people. The parasite, however, does not respond to treatment with standard leishmaniasis drugs. The research was conducted by scientists at the Federal Universities of Sergipe and São Carlos, the University of São Paulo, and the Oswaldo Cruz Foundation, all in Brazil, along with investigators at the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health.
Leishmaniasis is a parasitic disease found in parts of the tropics, subtropics, and southern Europe. It is classified as a neglected tropical disease and is often transmitted by the bite of some sand flies. The most common forms of leishmaniasis are cutaneous, which causes skin sores, and visceral, which affects several internal organs (usually spleen, liver, and bone marrow). According to the World Health Organization, each year between 50,000 and 90,000 people become sick with visceral leishmaniasis (kala-azar), a form of the disease that attacks the internal organs and is fatal in more than 95 percent of cases left untreated. During the last several decades, researchers have described rare cases of patients co-infected with both Leishmania and other groups of protozoan parasites that usually infect insects, including Crithidia. The current study of parasites isolated from a Brazilian patient confirms that Crithidia parasites also can infect people.
A female Anopheles albimanus mosquito taking a blood meal. Some Crithidia parasites are known to parasitize anopheline mosquitoes. Photo credit: CDC/James Gathany.
Redesigned MRI holds promise for the diagnosis and treatment of diseases
National Institutes of Health researchers, along with researchers at Siemens, have developed a high-performance, low magnetic-field MRI system that vastly improves image quality of the lungs and other internal structures of the human body. The new system is more compatible with interventional devices that could greatly enhance image-guided procedures that diagnose and treat disease, and the system makes medical imaging more affordable and accessible for patients.
The low-field MRI system may also be safer for patients with pacemakers or defibrillators, quieter, and easier to maintain and install. The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appears today in the journal Radiology.
The trend in recent years has been to develop MRI systems with higher magnetic field strengths to produce clearer images of the brain. But, researchers calculated that using those same state-of-the-art systems — at a modified strength — might offer high quality imaging of the heart and lungs. They found that metal devices such as interventional cardiology tools that were once at risk of heating with the high-field system were now safe for real-time, image-guided procedures such as heart catherization.
“We continue to explore how MRI can be optimized for diagnostic and therapeutic applications,” said Robert Balaban, Ph.D., scientific director of the Division of Intramural Research and chief of the Laboratory of Cardiac Energetics at NHLBI. “The system reduces the risk of heating — a major barrier to the use of MRI-guided therapeutic approaches that have hampered the imaging field for decades.”
Lung cysts and surrounding tissues in a patient with lymphangioleiomyomatosis (LAM) seen more clearly using high-performance low field MRI compared to standard MRI. Photo credit: Campbell-Washburn A E, Ramasawmy R, Restivo M C, et al. Used by permission.
Pregnant women who are exposed to higher air pollution levels during their second pregnancy, compared to their first one, may be at greater risk of preterm birth, according to researchers at the National Institutes of Health. Their study appears in the International Journal of Environmental Research and Public Health.
Preterm birth, or the birth of a baby before 37 weeks, is one of the leading causes of infant mortality in the United States, according to the Centers for Disease Control and Prevention. Although previous studies have found an association between air pollution exposure and preterm birth risk, the authors believe their study is the first to link this risk to changes in exposure levels between a first and second pregnancy.
“What surprised us was that among low-risk women, including women who had not delivered preterm before, the risk during the second pregnancy increased significantly when air pollution stayed high or increased,” said Pauline Mendola, Ph.D., the study’s lead author and a senior investigator in the Epidemiology Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Two-pronged approach stymies AML escape plan, could have applications to many cancers
Scientists from the National Institutes of Health and Cincinnati Children’s Hospital Medical Center have devised a potential treatment against a common type of leukemia that could have implications for many other types of cancer. The new approach takes aim at a way that cancer cells evade the effects of drugs, a process called adaptive resistance.
The researchers, in a range of studies, identified a cellular pathway that allows a form of acute myeloid leukemia (AML), a deadly blood and bone marrow cancer, to elude the activity of a promising class of drugs. They then engineered a compound that appears to launch a two-pronged attack against the cancer. In several experiments, the compound blocked a mutant protein that causes the AML. At the same time, it halted the cancer cells’ ability to sidestep the compound’s effects. The results, reported Sept. 4 in Science Translational Medicine, could lead to the development of new therapies against AML and cancers that act in similar ways.
Co-corresponding authors Daniel Starczynowski, Ph.D., at Cincinnati Children’s, Craig Thomas, Ph.D., at NIH’s National Center for Advancing Translational Sciences (NCATS) and their colleagues wanted to better understand drug resistance in a form of AML caused by a mutant protein called FLT3. This form of AML accounts for roughly 25% of all newly diagnosed AML cases, and patients often have a poor prognosis. A more thorough understanding of the drug resistance process could help them find ways to improve therapy options.
The chemical structure of a prospective drug sitting inside the protein kinase IRAK4.
