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:
Saxophonist Joey Berkley was living his dream: he was playing jazz in New York City. But about 20 years ago, he noticed his left hand wasn’t cooperating. It got worse and worse.
“As soon as I picked my horn up and touched — literally just touched my horn — my hands would twist into pretzel shapes,” Berkley recalled in a conversation with Morning Edition host A Martinez.
Berkley was experiencing focal dystonia, a movement disorder marked by involuntary muscle contractions.
He said he “muscled through it” as best he could. But that meant he wasn’t just pressing down on the keys of his sax — he was crushing them. “My fingers would literally be bleeding afterwards,” he said. “I had to quit playing.”
Joey Berkley learned of an experimental procedure at the National Institutes of Health in Bethesda, Maryland, that involved placing an electrode directly into his brain.
NIH-supported findings suggest the need to expand definitions of addiction treatment success beyond abstinence
Reducing stimulant use was associated with significant improvement in measures of health and recovery among people with stimulant use disorder, even if they did not achieve total abstinence. This finding is according to an analysis(link is external) of data from 13 randomized clinical trials of treatments for stimulant use disorders involving methamphetamine and cocaine. Historically, total abstinence has been the standard goal of treatment for substance use disorders, however, these findings support the growing recognition that a more nuanced perspective on measuring treatment success may be beneficial.
The study, published in Addiction, was led by scientists at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in collaboration with researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.
Researchers found that transitioning from high use (five or more days a month) to lower use (one to four days a month) was associated with lower levels of drug craving, depression, and other drug-related challenges compared to no change in use. These results suggest that reduction in use of methamphetamine or cocaine, in addition to abstinence, is a meaningful surrogate or intermediate clinical outcome in medication development for stimulant addiction. Unlike other substance use disorders, such as opioid use disorder or alcohol use disorder, there are currently no U.S. Food and Drug Administration-approved pharmacological treatments for stimulant use disorders.
“These findings align with an evolving understanding in the field of addiction, affirming that abstinence should be neither the sole aim nor only valid outcome of treatment,” said NIDA Director Nora Volkow, M.D. “Embracing measures of success in addiction treatment beyond abstinence supports more individualized approaches to recovery, and may lead to the approval of a wider range of medications that can improve the lives of people with substance use disorders.”
Researchers at the National Institutes of Health have published an atlas of zebrafish development, detailing the gene expression programs that are activated within nearly every cell type during the first five days of development, a period in which embryos mature from a single cell into distinct cell types. These diverse cells become tissues and organs that form juvenile fish capable of swimming and looking for food. The findings are published in Developmental Cell.
“Perhaps surprisingly, tiny zebrafish provide us with significant insight into human development and disease. Many of the gene expression programs that direct embryonic growth are similar across fish, people, and other animals,” said Christopher McBain, Ph.D., scientific director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which conducted the work. “Since zebrafish are visibly transparent, fertilize eggs externally, and are easy to study genetically, they represent a unique and effective way to model human disease.”
The process of embryonic development is orchestrated by instructions in DNA that direct different programs of gene expression within individual cells, which give different cell types their unique functional characteristics. To create the atlas, the study team used a method called single-cell RNA sequencing to identify gene expression programs over the course of five days, with samples taken every two to 12 hours. The resulting atlas follows nearly 490,000 cells continuously over 120 hours after fertilization, with an average of 8,621 transcripts and 1,745 genes detected per cell. The study team then sorted these data among known cell types and cell states during development.
BEST4+ cells are labelled red along the zebrafish gastrointestinal tract. These understudied cells are linked to gastrointestinal diseases and cancer in people.
W. Kimryn Rathmell, M.D., Ph.D., began work today as the 17th director of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). A renowned kidney cancer expert and influential leader in cancer research and patient care, Dr. Rathmell was selected by President Biden to succeed Monica M. Bertagnolli, M.D., who left NCI to become the NIH director on November 9.
“I want to officially welcome Dr. Rathmell to the National Cancer Institute on her first day as director,” said Department of Health and Human Services Secretary Xavier Becerra. “Dr. Rathmell begins her new role at an important time. The President and First Lady reignited the Biden Cancer Moonshot℠ to dramatically accelerate progress in the fight against cancer—and NCI is helping to lead the charge. Dr. Rathmell brings decades of experience helping to advance research and drive innovation to improve care for patients. She joins an extraordinary team already doing great work to prevent, detect, and treat cancer to make sure Americans are living longer, healthier lives. I look forward to working closely with Dr. Rathmell in the months and years ahead to help end cancer as we know it.”
“I am thrilled to welcome Dr. Rathmell to NIH, and I know she is the right leader at the right time for NCI,” said Dr. Bertagnolli. “She is a fantastic combination of researcher and clinician who deeply understands the process of translating lab research into effective cancer treatments. NCI is in great hands to actualize the brighter future we all want for people with cancer.”
Study suggests greater CD8+ T-cell activity may increase HIV immunity
An effective HIV vaccine may need to prompt strong responses from immune cells called CD8+ T cells to protect people from acquiring HIV, according to a new study from researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues. The study findings, appearing in Science, draw comparisons between the immune system activity of past HIV vaccine study participants and people with HIV who naturally keep the virus from replicating even in the absence of antiretroviral therapy (ART). The latter individuals are often called “long-term non-progressors” or “elite controllers” (LTNPs/ECs).
When HIV enters the body, the virus begins to damage the immune system by inserting itself into CD4+ T cells, which are white blood cells that help coordinate the immune response to pathogens. In most people, HIV continues to replicate and damage more and more CD4+ T cells unless controlled by ART. Among LTNPs/ECs, the immune system appears to promptly recognize CD4+ cells with HIV and activate other immune cells called CD8+ T cells. CD8+ T cells destroy CD4+ cells with HIV, enabling the suppression of HIV in a person’s blood.
The aim of an effective HIV vaccine is to provide durable protective immunity to HIV, or if initial defenses are bypassed, to help control HIV in the body long term, as happens with LTNPs/ECs. Although several preventive HIV vaccine candidates have been designed to stimulate CD8+ T-cell activity, they did not prevent HIV acquisition or control viral replication in clinical trials. Understanding and addressing this lack of effect is a scientific priority of HIV vaccine research.
Scientists in the HIV-Specific Immunity Section of NIAID’s Laboratory of Immunoregulation and colleagues designed their study to better understand which CD8+ T-cell functions were lacking in previous HIV vaccine recipients. They compared laboratory samples from previous HIV vaccine study participants with samples from LTNPs/ECs. They found that both HIV vaccine recipients and LTNPs/ECs generated large numbers of CD8+ T cells that recognized HIV. However, unlike the CD8+ T cells of LTNPs/ECs, HIV vaccine recipients’ CD8+ T cells failed to deliver the proteins necessary to destroy HIV-infected CD4+ T cells with HIV.
Layout featuring colorized 3D prints of HIV virus particles (pink with teal surface proteins) and a background image that is a colorized transmission electron micrograph of HIV virus particles (pink) budding and replicating from an H9 T cell (purple). Micrograph captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Note: not to scale.
Genome topology map of human retina development lays foundation for understanding diverse clinical phenotypes in simple and complex eye diseases
Researchers at the National Institutes of Health have mapped the 3D organization of genetic material of key developmental stages of human retinal formation, using intricate models of a retina grown in the lab. The findings lay a foundation for understanding clinical traits in many eye diseases, and reveal a highly dynamic process by which the architecture of chromatin, the DNA and proteins that form chromosomes, regulates gene expression. The findings were published in Cell Reports.
“These results provide insights into the heritable genetic landscape of the developing human retina, especially for the most abundant cell types that are commonly associated with vision impairment in retinal diseases,” said the study’s lead investigator, Anand Swaroop, Ph.D., chief of the Neurobiology, Neurodegeneration, and Repair Laboratory at the National Eye Institute (NEI), part of NIH.
Using deep Hi-C sequencing, a tool used for studying 3D genome organization, the researchers created a high-resolution map of chromatin in a human retinal organoid at five key points in development. Organoids are tissue models grown in a lab and engineered to replicate the function and biology of a specific type of tissue in a living body.
This image metaphorically captures the cell differentiation process during retinal organoid development. Loose yarn representing uncompacted DNA is wound by a crochet hook around buttons representing nucleosomes and culminating in a tightly condensed ball of chromatin that forms an eye-like shape.
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.”
