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:
Among those aged 35 to 44, overdose mortality more than tripled during this period, NIH study reports
Drug overdose deaths rose markedly between January to June 2018 and July to December 2021 among 10- to 44-year-old girls and women who were pregnant or pregnant within the previous 12 months, according to a new study by researchers at National Institute on Drug Abuse (NIDA) at the National Institutes of Health. Overdose mortality more than tripled among those aged 35 to 44 during the study period, from 4.9 deaths per 100,000 mothers aged 35 to 44 with a live birth in the 2018 period to 15.8 in the 2021 period. Over 60% of these pregnancy-associated overdose deaths occurred outside healthcare settings, though often in counties with available healthcare resources, such as emergency and obstetric care. Published today in JAMA Psychiatry, the findings suggest that, while treatment is available to pregnant women with substance use disorders, significant barriers — such as penalization, stigma, discrimination, and limited socioeconomic resources — may obstruct the path to care, the authors note.
“The stigma and punitive policies that burden pregnant women with substance use disorder increase overdose risk by making it harder to access life-saving treatment and resources,” said Nora Volkow, M.D., NIDA Director and senior author on the study. “Reducing barriers and the stigma that surrounds addiction can open the door for pregnant individuals to seek and receive evidence-based treatment and social support to sustain their health as well as their child’s health.”
Monica M. Bertagnolli, M.D., started today as the 17th director of the National Institutes of Health, the nation’s biomedical research agency and largest public funder of biomedical research in the world. She is the first surgeon and the second woman to hold the position. Nominated by President Biden, Dr. Bertagnolli was confirmed on a bipartisan basis by the U.S. Senate on November 7. She transitioned from her role as the 16th director of the National Cancer Institute, a position she has held since October 2022. NCI Principal Deputy Director Douglas R. Lowy, M.D., will serve as the NCI acting director until President Biden appoints a new director.
In his nomination announcement earlier this year, President Biden stated: “Dr. Bertagnolli has spent her career pioneering scientific discovery and pushing the boundaries of what is possible to improve cancer prevention and treatment for patients and ensuring that patients in every community have access to quality care. Dr. Bertagnolli is a world-class physician-scientist whose vision and leadership will ensure NIH continues to be an engine of innovation to improve the health of the American people.”
Growing up in rural Wyoming, Dr. Bertagnolli experienced and saw firsthand the challenges faced by rural communities to access medical care and participate in medical research. Due to that lived experience, equity is a core value that drives all her efforts, which includes ensuring NIH research is equitable and accessible to all people from all walks of life regardless of income or zip code.
“As a physician-scientist for more than 30 years, I have seen the transformative power of NIH research to produce results that save lives, including my own treatment for breast cancer,” said Dr. Bertagnolli. “As NIH director, I look forward to ensuring that NIH continues to be the steward of our nation’s medical research while engaging all people and communities in the research effort that includes informing medical practice that drives equitable access to health care for all.”
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.
