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:
Whether you’re shedding pounds with the help of effective new medicines, slimming down after weight loss surgery or cutting calories and adding exercise, there will come a day when the numbers on the scale stop going down, and you hit the dreaded weight loss plateau.
In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, looked at when weight loss typically stops depending on the method people were using todrop pounds. He broke down the plateau into mathematical models using data from high-quality clinical trials of different ways to lose weight to understand why people stop losing when they do. The study published Monday in the journal Obesity.
NIH study suggests the brain’s 'salience network' is important for understanding substance use disorder, could be a future therapeutic target
Results from a new clinical trial suggest that a group of brain regions known as the 'salience network' is activated after a drug is taken intravenously, but not when that same drug is taken orally. When drugs enter the brain quickly, such as through injection or smoking, they are more addictive than when they enter the brain more slowly, such as when they are taken orally. However, the brain circuits underlying these differences are not well understood. This study offers new information that helps explain what may be causing this difference.
“We’ve known for a long time that the faster a drug enters the brain, the more addictive it is – but we haven’t known exactly why. Now, using one of the newest and most sophisticated imaging technologies, we have some insight,” said Nora Volkow, M.D., NIDA Director, chief of the NIAAA Laboratory of Neuroimaging, and senior author on the study. “Understanding the brain mechanisms that underlie addiction is crucial for informing prevention interventions, developing new therapies for substance use disorders, and addressing the overdose crisis.”
A biomarker of norepinephrine deficiency in the heart may help to detect Lewy body diseases before symptoms appear
In a small study, researchers at the National Institutes of Health have found that positron emission tomography (PET) scans of the heart may identify people who will go on to develop Parkinson’s disease or Lewy body dementia among those at-risk for these diseases. The findings, published in the Journal of Clinical Investigation and led by scientists at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH, may advance efforts to detect the earliest changes that years later lead to Parkinson’s disease and Lewy body dementia.
In 34 people with Parkinson’s disease risk factors, researchers conducted PET scans of the heart to gain insight into levels of the neurotransmitter norepinephrine. They found that the scans could distinguish individuals who would later be diagnosed with Parkinson’s or Lewy body dementia — both are brain diseases caused by abnormal deposits of the protein alpha-synuclein that form clumps known as Lewy bodies. The research was conducted at the NIH Clinical Center, currently the only location for 18F-dopamine PET scanning.
Norepinephrine is derived from dopamine, which is deficient in the brains of people with Parkinson’s disease. Earlier work from David S. Goldstein, M.D., Ph.D., NINDS Principal Investigator, demonstrated that people with Lewy body diseases had severe depletion of cardiac norepinephrine, which is normally released by the nerves that supply the heart.
In the present study, the research team led by Dr. Goldstein found that at-risk individuals with low 18F-dopamine-derived radioactivity in the heart were highly likely to develop Parkinson’s or Lewy body dementia during long-term follow-up, compared to individuals with the same risk factors but with normal radioactivity. PET scans work by using a radioactive tracer to visualize metabolic or biochemical processes in body organs.
Heart and brain PET scans from a study participant who developed Parkinson’s disease support a 'body first' progression. The top pair of PET scans image show low 18F-dopamine-derived radioactivity in the heart (right, with 13N-ammonia PET scan on left). Later, brain scans showed a loss of dopamine-producing neurons and the individual developed symptoms of the disease.
NIH study finds that failing to account for mixed genetic lineages could lead to inaccuracies
Researchers have found that previous studies analyzing the genomes of people with European ancestry may have reported inaccurate results by not fully accounting for population structure. By considering mixed genetic lineages, researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, demonstrated that previously inferred links between a genomic variant that helps digest lactose and traits such as a person’s height and cholesterol level may not be valid.
The study, published in Nature Communications, shows that people with European ancestry, who were previously treated as a genetically homogenous group in large-scale genetic studies, have clear evidence of mixed genetic lineages, known as admixture. As such, the results from previous genome-wide association studies that do not account for admixture in their examinations of people with European ancestry should be re-evaluated.
“By reading population genetics papers, we realized that the pattern of genetic makeup in Europe is too detailed to be viewed on a continental level,” said Daniel Shriner, Ph.D., staff scientist in the NIH Center for Research on Genomics and Global Health and senior author of the study. “What is clear based on our analysis, is when data from genetic association studies of people of European ancestry are evaluated, researchers should adjust for admixture in the population to uncover true links between genomic variants and traits.”
Early research in animal models shows potential against cervical cancer and neuroblastoma
Researchers at the National Institutes of Health have developed a way to potentially increase the effectiveness of T cell–based immunotherapy treatments, such as CAR T-cell therapy, against solid tumors. T cells are specialized white blood cells of the immune system that eliminate infected or abnormal cells. In animal studies, the enhanced T-cell therapies were effective against cervical cancer and neuroblastoma, a common solid tumor in children. The findings, by scientists at the National Cancer Institute (NCI), part of NIH, appear Nov. 1, 2023, in Clinical Cancer Research.
CAR T-cell therapy is a form of cellular immunotherapy that involves engineering T cells in the laboratory so they can specifically target and kill tumors. CAR T-cell therapy has been successful in treating blood cancers, but it hasn’t worked well for solid tumors. To improve the effectiveness of T-cell therapy against solid tumors, researchers at NCI’s Center for Cancer Research engineered T cells (CAR T cells and another form of cellular immunotherapy called TCR T cells) to carry cytokines, which are proteins that can boost T-cell function.
In laboratory studies, CAR and TCR T cells modified to express the cytokines IL-15 and IL-21 on their surface killed far more cancer cells than T cells carrying just one of these cytokines or neither of them. Previous research has found that treating patients with large amounts of cytokines caused severe, potentially fatal, side effects. The new approach aims to deliver this cytokine boost in a much more targeted way.
Colorized scanning electron micrograph of a T lymphocyte, also known as a T cell (blue).
Awarded by the President of the United States, the National Medal of Technology and Innovation recognizes outstanding contributions to America’s economic, environmental, and social well-being. Dr. Rosenberg will receive his medal from President Biden at a White House ceremony on October 24, 2023. The distinguished oncologist is among nine individuals and a team of three receiving the award this year.
Dr. Rosenberg helped pioneer the development of immunotherapy, a form of treatment that helps a person’s own immune system fight cancer. He identified the anti-cancer properties of a hormone, interleukin-2, that became the first cancer immunotherapy approved by the U.S. Food and Drug Administration.
NIH study suggests a small reduction in daily calories is beneficial for wellness
Reducing overall calorie intake may rejuvenate your muscles and activate biological pathways important for good health, according to researchers at the National Institutes of Health and their colleagues. Decreasing calories without depriving the body of essential vitamins and minerals, known as calorie restriction, has long been known to delay the progression of age-related diseases in animal models. This new study, published in Aging Cell, suggests the same biological mechanisms may also apply to humans.
Researchers analyzed data from participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), a study supported by the National Institute on Aging (NIA) that examined whether moderate calorie restriction conveys the same health benefits seen in animal studies. They found that during a two-year span, the goal for participants was to reduce their daily caloric intake by 25%, but the highest the group was able to reach was a 12% reduction. Even so, this slight reduction in calories was enough to activate most of the biological pathways that are important in healthy aging.
"A 12% reduction in calorie intake is very modest," said corresponding author and NIA Scientific Director Luigi Ferrucci, M.D., Ph.D. "This kind of small reduction in calorie intake is doable and may make a big difference in your health."
Blood calcium levels normalized in clinical trial participants
An investigational drug, encaleret, restored calcium levels in people with autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic disorder marked by an imbalance of calcium in the blood and urine, as well as abnormally low levels of parathyroid hormone, which regulates blood calcium levels. Led by clinician-scientists from the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health’s Clinical Center, results from the clinical trial are published in the New England Journal of Medicine.
In the mid-phase clinical trial, 13 participants with ADH1 received oral doses of the investigational drug for about 24 weeks. By the end of the trial, the treatment restored every participant’s blood calcium level to normal, and urine calcium approached normal levels. Levels of parathyroid hormone also normalized.
“It was amazing to see that every participant responded to the treatment. In literally minutes after taking the medication orally, the levels of parathyroid hormone increased dramatically,” said senior author and NIDCR endocrinologist Michael Collins, M.D.
NIDCR Senior Research Physician, Rachel I. Gafni, M.D., examines a clinical trial participant with ADH1, a rare genetic disorder marked by abnormally low levels of calcium in the blood.
Novel conditioning agent shows promise in animal models of sickle cell disease
Researchers at the National Institutes of Health have created a novel gene therapy procedure that could preserve fertility in people with sickle cell disease and other genetic blood conditions. Infertility is a high-risk and long-term side effect associated with current bone marrow transplantation and gene therapy approaches to treat sickle cell disease. It is a common reason people of reproductive age give for not pursuing these therapies.
The study, which appears in Nature Communications, describes the successful testing in animals of an antibody-drug conjugate, or conditioning agent, that exclusively targets blood-forming stem cells in the bone marrow. Conditioning agents are used in gene therapy to remove diseased stem cells and allow healthy stem cells to form. This new agent, called CD117-ADC, does not appear to damage other organs during the conditioning process. It is less toxic than the conventional agent now used for gene therapy in humans, called busulfan, which may cause ovarian failure in women and may stop sperm production in men, resulting in infertility.
NIH study reviews 25 years of data and finds AI/ML can detect common hormone disorder
Artificial intelligence (AI) and machine learning (ML) can effectively detect and diagnose Polycystic Ovary Syndrome (PCOS), which is the most common hormone disorder among women, typically between ages 15 and 45, according to a new study by the National Institutes of Health. Researchers systematically reviewed published scientific studies that used AI/ML to analyze data to diagnose and classify PCOS and found that AI/ML based programs were able to successfully detect PCOS.
“Given the large burden of under- and mis-diagnosed PCOS in the community and its potentially serious outcomes, we wanted to identify the utility of AI/ML in the identification of patients that may be at risk for PCOS,” said Janet Hall, M.D., senior investigator and endocrinologist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and a study co-author. “The effectiveness of AI and machine learning in detecting PCOS was even more impressive than we had thought.”
PCOS occurs when the ovaries do not work properly, and in many cases, is accompanied by elevated levels of testosterone. The disorder can cause irregular periods, acne, extra facial hair, or hair loss from the head. Women with PCOS are often at an increased risk for developing type 2 diabetes, as well as sleep, psychological, cardiovascular, and other reproductive disorders such as uterine cancer and infertility.
“PCOS can be challenging to diagnose given its overlap with other conditions,” said Skand Shekhar, M.D., senior author of the study and assistant research physician and endocrinologist at the NIEHS. “These data reflect the untapped potential of incorporating AI/ML in electronic health records and other clinical settings to improve the diagnosis and care of women with PCOS.”
NIH researchers combined historical air quality data with breast cancer data from large U.S. study
Researchers at the National Institutes of Health found that living in an area with high levels of particulate air pollution was associated with an increased incidence of breast cancer. The study, published in the Journal of the National Cancer Institute, is one of the largest studies to date looking at the relationship between outdoor air pollution, specifically fine particulate matter, and breast cancer incidence. The research was done by scientists at the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), both part of NIH.
The researchers saw that the largest increases in breast cancer incidence was among women who on average had higher particulate matter levels (PM2.5) near their home prior to enrolling in the study, compared to those who lived in areas with lower levels of PM2.5. Particulate matter is a mixture of solid particles and liquid droplets found in the air. It comes from numerous sources, such as motor vehicle exhaust, combustion processes (e.g., oil, coal), wood smoke/vegetation burning, and industrial emissions. The particulate matter pollution measured in this study was 2.5 microns in diameter or smaller (PM2.5), meaning the particles are small enough to be inhaled deep into the lungs. The Environmental Protection Agency has a website known as Air Now where residents can enter their zip code and get the air quality information, including PM2.5 levels, for their area.
“We observed an 8 percent increase in breast cancer incidence for living in areas with higher PM2.5 exposure. Although this is a relatively modest increase, these findings are significant given that air pollution is a ubiquitous exposure that impacts almost everyone,” said Alexandra White, Ph.D., lead author and head of the Environment and Cancer Epidemiology Group at NIEHS. “These findings add to a growing body of literature suggesting that air pollution is related to breast cancer.”
