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.
AAAS is the world’s largest general scientific society and publisher of the Science family of journals. Newly elected fellows are recognized for scientific and socially notable achievements spanning their careers. Election is one of the most distinguished honors in the scientific community.
AAAS fellows have been recognized for their achievements across disciplines —from research, teaching and technology, to administration in academia, industry and government, to excellence in communicating and interpreting science to the public.
AAAS first launched this lifetime recognition in 1874. Individuals are elected annually by the AAAS council. New fellows are recognized at a ceremonial forum during the AAAS annual meeting, where they are presented with a certificate and blue and gold rosette.
Clockwise from top-left: Dr. Jürgen Wess, Dr. Stephen Chanock, Dr. Erin Lavik, Dr. Julie Segre, Dr. Daniel Reich, and Dr. Gisela Storz
NIH researchers suggest conducting nail evaluation of affected patients and at-risk family members
Scientists at the National Institutes of Health (NIH) have discovered that the presence of a benign nail abnormality may lead to the diagnosis of a rare inherited disorder that increases the risk of developing cancerous tumors of the skin, eyes, kidneys and the tissue that lines the chest and abdomen (e.g., the mesothelium). The condition, known as BAP1 tumor predisposition syndrome, is caused by mutations in the BAP1 gene, which normally acts as a tumor suppressor, among other functions. The findings are published in JAMA Dermatology and will be presented today at the Society for Investigative Dermatology Annual Meeting in Dallas.
Scientists happened upon the discovery while studying participants who were enrolled in a screening for BAP 1 variants at the NIH Clinical Center. As part of the study, a dermatology screening was performed at enrollment and annually for participants aged 2 and older. The cohort in the current study included 47 individuals with BAP1 tumor predisposition syndrome from 35 families.
“When asked about nail health during a baseline genetic assessment, a very astute patient reported that he had noticed subtle changes in his nails,” said co-lead author and genetic counselor Alexandra Lebensohn, M.S., of NIH’s National Cancer Institute (NCI). “His comment prompted us to systematically evaluate other participants for nail changes and uncover this new finding.”
Study of cerebral organoids reinforces evidence for substantial species barrier
A new study of prion diseases, using a human cerebral organoid model, suggests there is a substantial species barrier preventing transmission of chronic wasting disease (CWD) from cervids — deer, elk and moose — to people. The findings, from National Institutes of Health scientists and published in Emerging Infectious Diseases, are consistent with decades of similar research in animal models at the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
Prion diseases are degenerative diseases found in some mammals. These diseases primarily involve deterioration of the brain but also can affect the eyes and other organs. Disease and death occur when abnormal proteins fold, clump together, recruit other prion proteins to do the same, and eventually destroy the central nervous system. Currently, there are no preventive or therapeutic treatments for prion diseases.
CWD is a type of prion disease found in cervids, which are popular game animals. While CWD has never been found in people, a question about its transmission potential has lingered for decades: Can people who eat meat from CWD-infected cervids develop prion disease? The question is important because during the mid-1980s and mid-1990s a different prion disease – bovine spongiform encephalopathy (BSE), or mad cow disease – emerged in cattle in the United Kingdom (U.K.) and cases also were detected in cattle in other countries, including the United States. Over the next decade, 178 people in the U.K. who were thought to have eaten BSE-infected beef developed a new form of a human prion disease, variant Creutzfeldt-Jakob Disease, and died. Researchers later determined that the disease had spread among cattle through feed tainted with infectious prion protein. The disease transmission path from feed to cattle to people terrified U.K. residents and put the world on alert for other prion diseases transmitted from animals to people, including CWD. CWD is the most transmissible of the prion disease family, showing highly efficient transmission between cervids.
A researcher holds a flask containing human cerebral organoids similar to those used in the CWD study.
NIH-led findings point to a biomarker for rare disorders associated with the gene PNPLA6
Led by researchers at the National Institutes of Health (NIH), a team of scientists has uncovered the complex molecular mechanisms underlying neurodegenerative disorders linked to the gene PNPLA6, which encompass a range of conditions affecting mobility, vision, and hormonal regulation. Published in the journal BRAIN, the research offers a deeper understanding of PNPLA6-related conditions at clinical, genetic, and molecular levels, paving the way for tailored diagnostic and therapeutic approaches.
PNPLA6-related disorders arise due to mutations that impair the function of an enzyme involved in the regulation of lipid metabolism and membrane stability within neurons, known as neuropathy target esterase (NTE). Inhibition of NTE activity has been linked to neurological disorders such as organophosphate-induced delayed neuropathy, hereditary spastic paraplegia, Boucher-Neuhäuser syndrome and Oliver-McFarlane syndrome.
Robert Hufnagel, M.D., Ph.D., and colleagues at the NIH’s National Eye Institute (NEI) Ophthalmic and Visual Function Branch, conducted a systematic review and analysis of data from more than 100 patients with PNPLA6 mutations. Using neuroimaging, electrophysiological studies (where neurons’ electrical signals are measured and analyzed to understand their function and properties), and genetic testing information, the researchers meticulously evaluated mobility, vision, and hormone expression.
NTE helps regulate lipid metabolism and membrane stability within neurons. Mutations in the PNPLA6 gene inhibit NTE activity, leading to neurological disorders.
Federal study shows lives lost from overdose crisis are felt across generations, emphasizing need to include children and families in support
An estimated 321,566 children in the United States lost a parent to drug overdose from 2011 to 2021, according to a study(link is external) published in JAMA Psychiatry. The rate of children who experienced this loss more than doubled during this period, from approximately 27 to 63 children per 100,000. The highest number of affected children were those with non-Hispanic white parents, but communities of color and tribal communities were disproportionately affected. The study was a collaborative effort led by researchers at the National Institutes of Health’s (NIH) National Institute on Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), and the Centers for Disease Control and Prevention (CDC).
Children with non-Hispanic American Indian/Alaska Native parents consistently experienced the highest rate of loss of a parent from overdose from 2011 to 2021 — with 187 per 100,000 children affected in this group in 2021, more than double the rate among non-Hispanic white children (76.5 per 100,000) and among non-Hispanic Black children (73 per 100,000). While the number of affected children increased from 2011 to 2021 across all racial and ethnic populations, children with young non-Hispanic Black parents (18 to 25 years old) experienced the highest — roughly 24% — increase in rate of loss every year. Overall, children lost more fathers than mothers (192,459 compared to 129,107 children) during this period.
“It is devastating to see that almost half of the people who died of a drug overdose had a child. No family should lose their loved one to an overdose, and each of these deaths represents a tragic loss that could have been prevented,” said Nora Volkow, M.D., NIDA director. “These findings emphasize the need to better support parents in accessing prevention, treatment, and recovery services. In addition, any child who loses a parent to overdose must receive the care and support they need to navigate this painful and traumatic experience.”
NIH-led study finds genetic markers that explain up to 12 percent of the differences between two people’s blood pressure
National Institutes of Health researchers and collaborators have discovered over 100 new regions of the human genome, also known as genomic loci, that appear to influence a person’s blood pressure. Results of the study also point to several specific genomic loci that may be relevant to iron metabolism and a type of cellular receptor known as adrenergic receptors.
The study, published in Nature Genetics, is one of the largest such genomic studies of blood pressure to date, including data from over 1 million participants and laying the groundwork for researchers to better understand how blood pressure is regulated. Such insights could point to potential new drug targets.
“Our study helps explain a much larger proportion of the differences between two people’s blood pressure than was previously known,” said Jacob Keaton, Ph.D., staff scientist in the Precision Health Informatics Section within the National Human Genome Research Institute’s (NHGRI) Intramural Research Program and first author of the study. “Our study found additional genomic locations that together explain a much larger part of the genetic differences in people’s blood pressure. Knowing a person's risk for developing hypertension could lead to tailored treatments, which are more likely to be effective.”
In a new analysis of genetic susceptibility to kidney cancer, an international team of researchers has identified 50 new areas across the genome that are associated with the risk of developing kidney cancer. These insights could one day be used to advance our understanding of the molecular basis of kidney cancer, inform screening efforts for those at highest risk, and identify new drug targets. The study was led by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).
A previous genome-wide association study (GWAS) of people of European ancestry identified 13 regions of the genome that are associated with kidney cancer risk. However, the study population was not diverse. To identify additional regions, researchers conducted a GWAS in participants of many different genetic ancestries that included 29,020 people with kidney cancer and 835,670 people without kidney cancer. Analysis of the data, which came from published studies, biobanks, and a new study, resulted in the identification of 50 new regions associated with the risk of developing kidney cancer, bringing the total number of such regions to 63.
Among the newly identified genetic variants were several associated with a risk of developing papillary renal cell carcinoma, the second most common subtype of renal cell carcinoma. Another variant, in the VHL gene, was common in individuals of African ancestry and was associated with an estimated three times higher risk of developing clear cell renal cell carcinoma, the most common type of kidney cancer.
One injected dose of an experimental malaria monoclonal antibody was 77% effective against malaria disease in children in Mali during the country’s six-month malaria season, according to the results of a mid-stage clinical trial. The trial assessed an investigational monoclonal antibody developed by scientists at the National Institutes of Health (NIH), and results appear in The New England Journal of Medicine.
“A long-acting monoclonal antibody delivered at a single health care visit that rapidly provides high-level protection against malaria in these vulnerable populations would fulfill an unmet public health need,” said Dr. Jeanne Marrazzo, director of the National Institute of Allergy and Infectious Diseases, part of NIH.
The clinical trial assessed two dose levels, with 19% of the 300mg-dose group and 28% of the 150mg-dose group developing symptomatic malaria, providing protective efficacy of 77% and 67% against symptomatic malaria, respectively. Among children who received placebo, 81% became infected with Plasmodium falciparum, and 59% had symptomatic malaria during the six-month study period. The authors note that the trial demonstrated for the first time that a single dose of a monoclonal antibody given by subcutaneous injection can provide high-level protection against malaria in children in an area of intense malaria transmission.
The experimental monoclonal antibody binds to and neutralizes 'sporozoites,' the form of the malaria parasite transmitted by mosquitoes that invades the liver to initiate infection.
NIH scientists find clinicians still rely often on older and toxic medicines
Despite Food and Drug Administration (FDA)-approval of seven next-generation antibiotics to fight infections caused by resistant “gram-negative” bacteria, clinicians frequently continue to treat antibiotic-resistant infections with older generic antibiotics considered to be less effective and less safe, according to a study by researchers at the National Institutes of Health’s (NIH) Clinical Center. Researchers examined the factors influencing doctors’ preference for newer antibiotics over traditional generic agents to shed light on the decision-making processes among clinicians when treating patients with challenging bloodstream infections caused by gram-negative bacteria and significant comorbidities.
The study revealed that at a considerable proportion of hospitals, particularly smaller facilities located in rural areas, staff were reluctant to adopt newer antibiotics. Researchers identified a large cost disparity between older and newer classes of antibiotics; the newer drugs can cost approximately six times more than the older medications, which could disincentivize prescribing.
Researchers also highlight that next-gen agents are prescribed more often at hospitals where lab results that show the medications are effective against a patient’s bacterial infection are reported to prescribers. Scientists suggest that earlier and more widespread availability of such lab testing might improve use. Additionally, authors recommend that future public health policies and economic strategies on further development and use of similar antibiotics should be designed to identify and overcome additional barriers.
Scanning electron micrograph of methicillin-resistant Staphylococcus aureus bacteria (red, round items) killing and escaping from a human white blood cell.
Proof-of-concept study analyzed a newer technology known as single-cell RNA sequencing
In a proof-of-concept study, researchers at the National Institutes of Health (NIH) have developed an artificial intelligence (AI) tool that uses data from individual cells inside tumors to predict whether a person’s cancer will respond to a specific drug. Researchers at the National Cancer Institute (NCI), part of NIH, published their work on April 18, 2024, in Nature Cancer, and suggest that such single-cell RNA sequencing data could one day be used to help doctors more precisely match cancer patients with drugs that will be effective for their cancer.
Current approaches to matching patients to drugs rely on bulk sequencing of tumor DNA and RNA, which takes an average of all the cells in a tumor sample. However, tumors contain more than one type of cell and in fact can have many different types of subpopulations of cells. Individual cells in these subpopulations are known as clones. Researchers believe these subpopulations of cells may respond differently to specific drugs, which could explain why some patients do not respond to certain drugs or develop resistance to them.
In contrast to bulk sequencing, a newer technology known as single-cell RNA sequencing provides much higher resolution data, down to the single-cell level. Using this approach to identify and target individual clones may lead to more lasting drug responses. However, single-cell gene expression data are much more costly to generate than bulk gene expression data and not yet widely available in clinical settings.
