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.
Such an algorithm may save clinicians time and accelerate clinical enrollment and research
Researchers from the National Institutes of Health (NIH) have developed an artificial intelligence (AI) algorithm to help speed up the process of matching potential volunteers to relevant clinical research trials listed on ClinicalTrials.gov. A study published in Nature Communications found that the AI algorithm, called TrialGPT, could successfully identify relevant clinical trials for which a person is eligible and provide a summary that clearly explains how that person meets the criteria for study enrollment. The researchers concluded that this tool could help clinicians navigate the vast and ever-changing range of clinical trials available to their patients, which may lead to improved clinical trial enrollment and faster progress in medical research.
A team of researchers from NIH’s National Library of Medicine (NLM) and National Cancer Institute harnessed the power of large language models (LLMs) to develop an innovative framework for TrialGPT to streamline the clinical trial matching process. TrialGPT first processes a patient summary, which contains relevant medical and demographic information. The algorithm then identifies relevant clinical trials from ClinicalTrials.gov for which a patient is eligible and excludes trials for which they are ineligible. TrialGPT then explains how the person meets the study enrollment criteria. The final output is an annotated list of clinical trials—ranked by relevance and eligibility—that clinicians can use to discuss clinical trial opportunities with their patient.
“Machine learning and AI technology have held promise in matching patients with clinical trials, but their practical application across diverse populations still needed exploration,” said NLM Acting Director, Stephen Sherry, PhD. “This study shows we can responsibly leverage AI technology so physicians can connect their patients to a relevant clinical trial that may be of interest to them with even more speed and efficiency.”
Findings could point to new ways to treat RAS-driven cancers
Researchers at the National Institutes of Health (NIH) and their collaborators have discovered a new way in which RAS genes, which are commonly mutated in cancer, may drive tumor growth beyond their well-known role in signaling at the cell surface. Mutant RAS, they found, helps to kick off a series of events involving the transport of specific nuclear proteins that lead to uncontrolled tumor growth, according to a study published Nov. 11, 2024, in Nature Cancer.
RAS genes are the second most frequently mutated genes in cancer, and mutant RAS proteins are key drivers of some of the deadliest cancers, including nearly all pancreatic cancers, half of colorectal cancers, and one-third of lung cancers. Decades of research have shown that mutant RAS proteins promote the development and growth of tumors by activating specific proteins at the cell surface, creating a constant stream of signals telling cells to grow.
“This is the first study to show that mutated RAS genes can promote cancer in an entirely new way,” said study author Douglas Lowy, M.D., deputy director of NIH’s National Cancer Institute (NCI). “The finding of the additional role for RAS proteins has exciting implications for improving treatment.”
Mutant RAS helps release EZH2 from a protein complex transported from the nucleus to the cytoplasm. Once released, EZH2 facilitates the breakdown of the DLC1 tumor suppressor protein, leading to uncontrolled tumor growth. Image created with BioRender.
A study from researchers at National Institutes of Health (NIH) and their collaborators revealed a significant genetic risk factor for kidney disease in people from Ghana and Nigeria. Their study demonstrated that having just one risk variant in a gene known as APOL1 can significantly increase the risk of developing kidney disease. APOL1 is important for the immune system and variants of the gene are linked to increased risk of chronic kidney disease. The study is published in the New England Journal of Medicine and was conducted by researchers from the Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network.
Previous research established that genomic variants in APOL1 increase the risk of developing chronic kidney disease among African Americans. However, not much is known about how these genomic variants affect people from West African countries, where many African Americans derive genetic ancestry. Studying how these genomic variants contribute to chronic kidney disease in West Africans and people with West African ancestry can also help inform the risk of kidney disease in many Americans.
“Our study provides data about West Africans that will help us better understand the risk of chronic kidney disease associated with APOL1 variants,” said Adebowale A. Adeyemo, M.B.B.S., who is a co-author of the study and is the deputy director and chief scientific officer of the Center for Research on Genomics and Global Health at NIH’s National Human Genome Research Institute (NHGRI). “By comparing this study to previous studies involving the African American population, we can gain a deeper understanding of the effects of these high risk APOL1 variants. Knowing your genetic risk for a disease, such as kidney disease, can help you make more informed decisions about your health and potentially lead to earlier interventions.”
Previous research established that genomic variants in APOL1 increase the risk of developing chronic kidney disease among African Americans.
NIH-supported findings pave the way for genetic testing, clinical trials, and therapy development
Scientists at the National Institutes of Health (NIH) and their colleagues have identified a gene responsible for some inherited retinal diseases (IRDs), which are a group of disorders that damage the eye’s light-sensing retina and threatens vision. Though IRDs affect more than 2 million people worldwide, each individual disease is rare, complicating efforts to identify enough people to study and conduct clinical trials to develop treatment. The study’s findings published today in JAMA Ophthalmology.
In a small study of six unrelated participants, researchers linked the gene UBAP1L to different forms of retinal dystrophies, with issues affecting the macula, the part of the eye used for central vision such as for reading (maculopathy), issues affecting the cone cells that enable color vision (cone dystrophy) or a disorder that also affects the rod cells that enable night vision (cone-rod dystrophy). The patients had symptoms of retinal dystrophy starting in early adulthood, progressing to severe vision loss by late adulthood.
“The patients in this study showed symptoms and features similar to other IRDs, but the cause of their condition was uncertain,” said Bin Guan, Ph.D., chief of the Ophthalmic Genomics Laboratory at NIH’s National Eye Institute (NEI) and a senior author of the report. “Now that we’ve identified the causative gene, we can study how the gene defect causes disease and, hopefully, develop treatment.”
Ophthalmic images from the study probands exhibit variable forms of retinal dystrophy.
NIH findings highlight critical gaps in treatment access in correctional facilities, where almost two-thirds of people have a substance use disorder
A new look into addiction treatment availability in the U.S. criminal justice system reveals that fewer than half (43.8%) of 1,028 jails surveyed across the nation offered any form of medication for opioid use disorder, and only 12.8% made these available to anyone with the disorder. With two-thirds of people who are incarcerated in U.S. jails experiencing a substance use disorder — in many cases, an opioid use disorder — the failure to make these medications widely available in criminal justice settings represents a significant missed opportunity to provide life-saving treatments in an environment where people in need of care can be easily reached.
The study, published in JAMA Network Open and supported by NIH’s National Institute on Drug Abuse (NIDA), also found that most jails did offer some type of substance use disorder treatment or recovery support (70.1%). The most common reason jails cited for not offering medications for opioid use disorder was lack of adequate licensed staff (indicated by 49.8% of jails). In general, larger jails, those in counties with lower 'social vulnerability' (lower levels of poverty and unemployment, and greater education, housing, and transportation access), and those with greater proximity to community-based providers of medications for opioid use disorder were more likely to offer these treatments.
“Offering substance use disorder treatment in justice settings helps to break the debilitating — and often fatal — cycle of addiction and incarceration,” said NIDA Director Nora D. Volkow, M.D. “Though someone may be in jail for only a short time, connecting them to addiction treatment while they are there is critical to reduce risk of relapse and overdose, and to help them achieve long-term recovery.”
Cancer incidence trends in 2021 largely returned to what they were before the COVID-19 pandemic, according to a study by researchers at the National Institutes of Health (NIH). However, there was little evidence of a rebound in incidence that would account for the decline in diagnoses in 2020, when screening and other medical care was disrupted. One exception was breast cancer, where the researchers did see an uptick in diagnoses of advanced-stage disease in 2021. The study appears Sept. 24, 2024, in the Journal of the National Cancer Institute.
A previous study showed that new cancer diagnoses fell abruptly in early 2020, as did the volume of pathology reports, suggesting that many cancers were not being diagnosed in a timely manner. To determine whether these missed diagnoses were caught in 2021, possibly as more advanced cancers, researchers from NIH’s National Cancer Institute (NCI) compared observed cancer incidence rates for 2021 with those expected from pre-pandemic trends using data from NCI’s Surveillance, Epidemiology, and End Results Program.
A full recovery in cancer incidence should appear as an increase over pre-pandemic levels (also known as a rebound) to account for the missed diagnoses. The researchers looked at cancer overall, as well as five major cancer types that vary in how they are typically detected: through screening (female breast and prostate cancer), due to symptoms (lung and bronchus and pancreatic cancer), or incidentally during other medical procedures (thyroid cancer).
Findings in animals suggest a surgery-free treatment for cataracts
Researchers at the National Institutes of Health (NIH) and their collaborators have identified a protein, known as RNF114, that reverses cataracts, a clouding of the eye’s lens that occurs commonly in people as they age. The study, which was conducted in the 13-lined ground squirrel and rats, may represent a possible surgery-free strategy for managing cataracts, a common cause of vision loss. The study published in the Journal of Clinical Investigation.
“Scientists have long searched for an alternative to cataract surgery, which is effective, but not without risk. Lack of access to cataract surgery is a barrier to care in some parts of the world, causing untreated cataracts to be a leading cause of blindness worldwide,” said Xingchao Shentu, M.D., a cataract surgeon and the co-lead investigator from Zhejiang University, China.
This new discovery was part of ongoing research at NIH’s National Eye Institute (NEI) involving a mammalian hibernator, the 13-lined ground squirrel. In these ground squirrels, the light-sensitive photoreceptor cells in the retina are mostly cones, which makes the ground squirrel helpful for studying cone-related properties, such as color vision. In addition, the squirrel’s ability to withstand months of cold and metabolic stress during hibernation make it model for vision scientists to study a range of eye diseases.
NIH clinical trial results expand treatment options for this disease
Results from a large clinical trial show that treatment with an immunotherapy drug may nearly double the length of time people with high-risk, muscle-invasive bladder cancer are cancer-free following surgical removal of the bladder. Researchers found that postsurgical treatment with pembrolizumab (Keytruda), which is approved by the Food and Drug Administration (FDA) for treating at least 18 different cancers, was superior compared with observation. The study, led by researchers at the National Institutes of Health (NIH), was published Sept. 15, 2024, in New England Journal of Medicine.
“This study shows that pembrolizumab can offer patients another treatment option to help keep their disease from coming back,” said lead investigator Andrea B. Apolo, M.D., of NIH’s National Cancer Institute (NCI) Center for Cancer Research. “Extending the time that these patients are cancer-free makes a big difference in their quality of life.”
A diagnosis of muscle-invasive bladder cancer means the tumor in the bladder has invaded into and through the muscular layer of tissue that encases the bladder. The standard treatment for this form of bladder cancer is to surgically remove the entire bladder. To improve the chances of successful surgery and of eliminating any cancer cells that may have already escaped from the tumor, patients are given cisplatin-based chemotherapy for a period before surgery, known as neoadjuvant therapy, or after surgery, known as adjuvant therapy.
Adjuvant pembrolizumab helps people with muscle-invasive bladder cancer remain cancer free longer than with observation alone.
Increased risk among men in disadvantaged neighborhoods may be linked to chronic stress
West African genetic ancestry was associated with increased prostate cancer among men living in disadvantaged neighborhoods but not among men living in more affluent neighborhoods, according to a new study led by researchers at the National Institutes of Health (NIH). The findings suggest that neighborhood environment may play a role in determining how genetic ancestry influences prostate cancer risk. The study was published Sept. 16, 2024, in JAMA Network Open.
In the United States, most Black Americans have West African genetic ancestry, the researchers noted. Previous studies have shown that West African genetic ancestry is linked to increased prostate cancer risk among Black men, whose risk is higher than that of any other U.S. population group. However, it is unclear whether additional factors play a role in determining this ancestry-related risk.
To explore how the neighborhood environment and West African genetic ancestry may act together in influencing prostate cancer risk, researchers at NIH’s Center for Cancer Research at the National Cancer Institute (NCI) conducted a study with long-term follow-up that included 1,469 self-identified Black and White men from the greater Baltimore area. The researchers determined the men’s West African ancestry through genetic markers and neighborhood socioeconomic status through factors such as unemployment rate, income level, and percentage of households in poverty.
Study finds that sickle cell trait is prevalent among diverse human populations
National Institutes of Health (NIH) researchers and collaborators have found that being a carrier for sickle cell disease, known as having sickle cell trait, increases the risk of blood clots, a risk that is the same among diverse human populations that may not traditionally be associated with sickle cell disease. The study provides estimated clinical risks for people with sickle cell trait, which can inform clinical practice guidelines. Researchers examined the largest and most diverse set of people with sickle cell trait to date, which includes data from over 19,000 people of various ancestral backgrounds with sickle cell trait.
The study, published in Blood Advances, was led by researchers at the National Human Genome Research Institute (NHGRI), part of NIH, The Johns Hopkins University School of Medicine, Baltimore, and the company 23andMe, South San Francisco, California.
Previous research investigating the relationship between sickle cell trait and blood clots have only included individuals of African genetic ancestry and self-identified Black participants because of the incorrect assumption that the genetic carrier state only affects those who identify as Black or African American. While sickle cell trait in the United States is most prevalent in individuals who self-identify as Black or African American, individuals from all ancestral backgrounds may have sickle cell trait. Sickle cell trait is often found in individuals living in or from West and Central Africa, Mediterranean Europe, India and the Middle East.
“Because sickle cell trait is often associated with people who identify as Black or African American, it is not widely studied in other populations, a bias that has led to unintended harm for those with sickle cell trait,” says Vence Bonham Jr., J.D., who co-led the study and serves as acting deputy director and associate investigator at NHGRI. “In particular, the racialization of sickle cell trait has resulted in biased estimations of health risks. The results of our study will help clinicians properly contextualize the risk of blood clots amongst people with sickle cell trait without unintended bias.”
