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.
In a proof-of-concept study, researchers at the National Institutes of Health (NIH) have developed an artificial intelligence (AI) tool that uses routine clinical data, such as that from a simple blood test, to predict whether someone’s cancer will respond to immune checkpoint inhibitors, a type of immunotherapy drug that helps immune cells kill cancer cells. The machine-learning model may help doctors determine if immunotherapy drugs are effective for treating a patient’s cancer. The study, published June 3, 2024, in Nature Cancer, was led by researchers at the National Cancer Institute’s (NCI) Center for Cancer Research and Memorial Sloan Kettering Cancer Center in New York. NCI is part of the National Institutes of Health.
Currently, two predictive biomarkers are approved by the Food and Drug Administration for use in identifying patients who may be candidates for treatment with immune checkpoint inhibitors. The first is tumor mutational burden, which is the number of mutations in the DNA of cancer cells. The second is PD-L1, a tumor cell protein that limits the immune response and is a target of some immune checkpoint inhibitors. However, these biomarkers do not always accurately predict response to immune checkpoint inhibitors. Recent machine-leaning models that use molecular sequencing data have shown value in predicting response, but this kind of data is expensive to obtain and not routinely collected.
The new study details a different kind of machine-learning model that makes predictions based on five clinical features that are routinely collected from patients: a patient’s age, cancer type, history of systemic therapy, blood albumin level, and blood neutrophil-to-lymphocyte ratio, a marker of inflammation. The model also considers tumor mutational burden, assessed through sequencing panels. The model was constructed and evaluated using data from multiple independent data sets that included 2,881 patients treated with immune checkpoint inhibitors across 18 solid tumor types.
NIH researchers find new pathways towards treatment for autoimmune polyendocrine syndrome type 1
A drug approved to treat certain autoimmune diseases and cancers successfully alleviated symptoms of a rare genetic syndrome called autoimmune polyendocrine syndrome type 1 (APS-1). Researchers identified the treatment based on their discovery that the syndrome is linked to elevated levels of interferon-gamma (IFN-gamma), a protein involved in immune system responses, providing new insights into the role of IFN-gamma in autoimmunity. The study, led by researchers at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, was published today in the New England Journal of Medicine.
In a three-stage study, conducted in mice and people, the researchers examined how APS-1 causes autoimmune disease. The syndrome is marked by dysfunction of multiple organs, usually beginning in childhood, and is fatal in more than 30% of cases. This inherited syndrome is caused by a deficiency in a gene that keeps the immune system’s T cells from attacking cells of the body, leading to autoimmunity; chronic yeast infections in the skin, nails, and mucous membranes; and insufficient production of hormones from endocrine organs, such as the adrenal glands. Symptoms include stomach irritation, liver inflammation, lung irritation, hair loss, loss of skin coloring, tissue damage, and organ failure.
In the first stage of this study, researchers led by scientists in NIAID’s Laboratory of Clinical Immunology and Microbiology examined the natural history of APS-1 in 110 adults and children. Blood and tissues were analyzed to compare gene and protein expression in people with and without APS-1. They found elevated IFN-gamma responses in the blood and tissues of people with APS-1, indicating that IFN-gamma may play an important role in the disease and providing a pathway to target for treatment.
Complete X and Y chromosome sequences from six primate species reveal species diversity and insights into evolution
A team of researchers funded by the National Institutes of Health have generated the first complete chromosome sequences from non-human primates. Published in Nature, these sequences uncover remarkable variation between the Y chromosomes of different species, showing rapid evolution, in addition to revealing previously unstudied regions of great ape genomes. Since these primate species are the closest living relatives to humans, the new sequences can provide insights into human evolution.
The researchers focused on the X and Y chromosomes, which play roles in sexual development and fertility, among many other biological functions. They sequenced chromosomes from five great ape species, chimpanzee, bonobo, gorilla and Bornean and Sumatran orangutans, as well as one other primate species that is more distantly related to humans, the siamang gibbon.
“These chromosome sequences add a significant amount of new information,” said Brandon Pickett, Ph.D., a postdoctoral fellow at the National Human Genome Research Institute (NHGRI), part of NIH, and an author of the study. “Only the chimpanzee genome sequence was fairly complete before this, but even that still had large gaps, especially in regions of repetitive DNA.”
Researchers compared the sequences of the ape chromosomes to the human X and Y chromosomes to understand their evolutionary histories.
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.
