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.
One dose of an antibody drug safely protected healthy, non-pregnant adults from malaria infection during an intense six-month malaria season in Mali, Africa, a National Institutes of Health clinical trial has found. The antibody was up to 88.2% effective at preventing infection over a 24-week period, demonstrating for the first time that a monoclonal antibody can prevent malaria infection in an endemic region. These findings were published today in The New England Journal of Medicine and presented at the American Society of Tropical Medicine & Hygiene 2022 Annual Meeting in Seattle.
“We need to expand the arsenal of available interventions to prevent malaria infection and accelerate efforts to eliminate the disease,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “These study results suggest that a monoclonal antibody could potentially complement other measures to protect travelers and vulnerable groups such as infants, children, and pregnant women from seasonal malaria and help eliminate malaria from defined geographical areas.”
NIAID sponsored and funded the trial, which was led by Peter D. Crompton, M.D., M.P.H., and Kassoum Kayentao, M.D., M.P.H., Ph.D. Dr. Crompton is chief of the Malaria Infection Biology and Immunity Section in the NIAID Laboratory of Immunogenetics, and Dr. Kayentao is a professor at the University of Sciences, Techniques and Technologies (USTTB) of Bamako, Mali.
An antibody drug called CIS43LS prevents malaria infection by interrupting the lifecycle of the Plasmodium falciparum parasite. The antibody binds to and neutralizes sporozoites, the stage of the parasite transmitted from mosquitos to humans.
A panel of investigational monoclonal antibodies (mAbs) targeting different sites of the Epstein-Barr virus (EBV) blocked infection when tested in human cells in a laboratory setting. Moreover, one of the experimental mAbs provided nearly complete protection against EBV infection and lymphoma when tested in mice. The results appear online today in the journal Immunity. Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in collaboration with researchers from Walter Reed Army Institute of Research, led the study.
EBV is one of the most common human viruses. After an EBV infection, the virus becomes dormant in the body but may reactivate in some cases. It is the primary cause of infectious mononucleosis and is associated with certain cancers, including Hodgkin lymphoma, and autoimmune diseases, such as multiple sclerosis. People with weakened immune systems, such as transplant recipients, are more likely than immunocompetent people to develop severe symptoms and complications from EBV infection. There is no licensed vaccine to protect against the virus.
The researchers developed several investigational mAbs targeting two key proteins—gH and gL—found on EBV’s surface. The two proteins are known to facilitate EBV fusion with human cells and cause infection. When tested in the laboratory setting, the investigational mAbs prevented EBV infection of human B cells and epithelial cells, which line the throat at the initial site of EBV infection. Analyzing the structure of the mAbs and their two surface proteins using X-ray crystallography and advanced microscopy, the researchers identified multiple sites of vulnerability on the virus to target. When tested in mice, one of the experimental mAbs, called mAb 769B10, provided almost complete protection against EBV infection when given. The mAb also protected all mice tested from EBV lymphoma.
An electron microscopy image showing three Epstein-Barr virions
Study may help lead to gene therapy for rare inherited blinding disease
Using a new stem-cell based model made from skin cells, scientists found the first direct evidence that Stargardt-related ABCA4 gene mutations affect a layer of cells in the eye called the retinal pigment epithelium (RPE). The discovery points to a new understanding of Stargardt disease progression and suggests a therapeutic strategy for the disease, which currently lacks treatment. The study took place at the National Eye Institute (NEI), part of the National Institutes of Health. The findings published online today in Stem Cell Reports.
“This new model will accelerate development of therapies for Stargardt disease,” said NEI Director Michael F. Chiang, M.D. “We lack a therapy for this disease in part because it’s rare. This model theoretically creates an unlimited supply of human cells for study.” Stargardt affects about 1 in every 10,000 people in the U.S.
Stargardt disease causes progressive loss of central and night vision. The vision loss is associated with the toxic build-up of lipid-rich deposits in the RPE, whose main job is to support and nourish the retina’s light sensing photoreceptors. Under normal conditions, the ABCA4 gene makes a protein that prevents this toxic build-up. Prior research showed that Stargardt disease is caused by a variety of mutations in the ABCA4 gene. More than 800 ABCA4 mutations are known to be associated with a broad spectrum of Stargardt disease phenotypes.
A cross section of the stem-cell generated RPE is shown after it has been fed photoreceptor outer segments. Arrows point to lipid deposits (green). This buildup of lipids is toxic to the cell, and similar to that seen in patients with Stargardt disease.
Scientists have discovered a mechanism by which an area of a protein shape-shifts to convert vitamin A into a form usable by the eye’s light-sensing photoreceptor cells. A previously uncharacterized area of the protein known as RPE65 spontaneously turns spiral-shaped when it encounters intracellular membranes, or thin structures that surround different parts of a cell.
This shapeshifting enables RPE65 to enter the endoplasmic reticulum — a network of sac-like structures and tubes — where RPE65 performs the crucial task of vitamin A conversion. The scientists say the discovery provides better understanding of RPE65’s function and will inform potential treatments for vision disorders linked to RPE65 gene mutations. Researchers at the National Eye Institute, part of the National Institutes of Health, conducted the research, which published in Life Science Alliance.
Women who used chemical hair straightening products were at higher risk for uterine cancer compared to women who did not report using these products, according to a new study from the National Institutes of Health. The researchers found no associations with uterine cancer for other hair products that the women reported using, including hair dyes, bleach, highlights, or perms.
The study data includes 33,497 U.S. women ages 35-74 participating in the Sister Study, a study led by the National Institute of Environmental Health Sciences (NIEHS), part of NIH, that seeks to identify risk factors for breast cancer and other health conditions. The women were followed for almost 11 years and during that time 378 uterine cancer cases were diagnosed.
The researchers found that women who reported frequent use of hair straightening products, defined as more than four times in the previous year, were more than twice as likely to go on to develop uterine cancer compared to those who did not use the products.
“We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%,” said Alexandra White, Ph.D., head of the NIEHS Environment and Cancer Epidemiology group and lead author on the new study. “This doubling rate is concerning. However, it is important to put this information into context - uterine cancer is a relatively rare type of cancer.”
NIH scientists shed light on how genetic architecture determines gene expression, tissue-specific function, and disease phenotype in blinding diseases
National Eye Institute researchers mapped the organization of human retinal cell chromatin, the fibers that package 3 billion nucleotide-long DNA molecules into compact structures that fit into chromosomes within each cell’s nucleus. The resulting comprehensive gene regulatory network provides insights into regulation of gene expression in general, and in retinal function, in both rare and common eye diseases. The study published in Nature Communications.
“This is the first detailed integration of retinal regulatory genome topology with genetic variants associated with age-related macular degeneration (AMD) and glaucoma, two leading causes of vision loss and blindness,” said the study’s lead investigator, Anand Swaroop, Ph.D., senior investigator and chief of the Neurobiology Neurodegeneration and Repair Laboratory at the NEI, part of the National Institutes of Health.
Using deep Hi-C sequencing, a tool used for studying 3D genome organization, the researchers created a high-resolution map of retinal cell chromatin contract points, shown left. The entire map included about 704 million contact points. Shown right, more than 60,000 chromatin loops are represented on a portion of the map.
Findings from a small study of eight patients published in Clinical Infectious Diseases suggest that COVID-19 rebound is likely not caused by impaired immune responses. The study, led by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, aimed to define the clinical course and the immunologic and virologic characteristics of COVID-19 rebound in patients who have taken nirmatrelvir/ritonavir (Paxlovid), an antiviral therapeutic developed by Pfizer, Inc. COVID-19 rebound is characterized by a recurrence of COVID-19 symptoms and/or a new positive viral test after having tested negative, according to the Centers for Disease Control and Prevention. According to the study authors, the results do not support the hypothesis that the five-day course of Paxlovid is too short for the body to develop a strong immune response to SARS-CoV-2, the virus that causes COVID-19.
Participants were selected from adults enrolled in an ongoing COVID-19 study at the NIH Clinical Center in Bethesda, Maryland, and other local hospitals. The study aims to better understand how SARS-CoV-2 affects white blood cells. Participants provide blood and other samples as well as access to their COVID-19 medical records as part of the study. The study to evaluate COVID-19 rebound included six participants (three men and three women with a median age of 42 years) who took Paxlovid within four days of initial symptom onset and then experienced recurrent symptoms; two participants (a 54-year-old man and 35-year-old woman) who experienced recurrent symptoms who did not take Paxlovid; and a control group of six people who had COVID-19 but did not experience symptom rebound. All participants were previously vaccinated and boosted against COVID-19, and none developed severe disease requiring hospitalization during acute infection or rebound. Investigators collected data on each participant’s clinical course and performed laboratory tests on blood and nasal swab samples.
Investigators found no evidence of genetic mutations that would suggest participants who experienced COVID-19 rebound were infected with a strain of SARS-CoV-2 that was resistant to Paxlovid. They also found no evidence of delayed development of antibodies in participants experiencing rebound after taking Paxlovid. Investigators detected robust SARS-CoV-2 T-cell responses in rebound patients. Overall, the level of T-cell responses was greater in rebound patients than in patients with early acute COVID-19 who did not experience rebound. Infectious SARS-CoV-2 was detected by viral culture in one out of eight rebound participants.
Colorized scanning electron micrograph of a cell infected with the Omicron strain of SARS-CoV-2 virus particles (purple), isolated from a patient sample.
Monica M. Bertagnolli, M.D., started today as the 16th director of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). She is the first woman to hold the position of NCI director. Dr. Bertagnolli succeeds Norman E. Sharpless, M.D., who stepped down as director in April 2022. Douglas R. Lowy, M.D., has been NCI’s acting director since April 30, 2022.
“I look forward to working with Dr. Bertagnolli to advance the President’s call to end cancer as we know it. Dr. Bertagnolli’s decades of cancer research expertise around patient-centered care and her work to create more inclusive clinical trials will be instrumental as we accelerate the rate of research and innovation to fight cancer,” said Secretary Xavier Becerra, U.S. Health and Human Services. “Cancer knows no bounds and neither should our efforts to prevent cancer deaths. Together, we will reignite and advance the President’s Cancer Moonshot initiative to save lives.”
“Dr. Bertagnolli brings exceptional experience to NIH as a surgical oncologist, professor, scientist and leader in the cancer research community,” said Lawrence A. Tabak, D.D.S., Ph.D., who is performing the duties of the NIH director. “She is ideally suited to lead NCI at a point in time when opportunities abound for major advancements in cancer research and cancer care.”
NCI Director Dr. Monica Bertagnolli. Photo courtesty of Brigham and Women’s Hospital
Former smokers who stick to a healthy lifestyle have a lower risk of dying from all causes than those who don’t engage in healthy habits, according to a new study by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The reduced risk of dying was observed for specific causes, including cancer and heart and lung diseases. Lifestyle interventions have not been robustly studied in former smokers, and these new findings could have important implications for the 52 million former smokers in the United States.
Maintaining a healthy lifestyle — defined as doing things such as being physically active and having a healthy diet — was associated with a 27% reduction in the risk of death over the 19-year follow-up period, compared with not maintaining a healthy lifestyle.
The findings, which appeared Sept. 22, 2022, in JAMA Network Open, come from an analysis of a large group of former smokers who participated in the NIH-AARP Diet and Health Study.
“I was surprised to see the robust associations [with lifestyle],” said Maki Inoue-Choi, Ph.D., of the Division of Cancer Epidemiology and Genetics at NCI, lead author of the paper. “Former smokers who adhered to evidence-based recommendations for body weight, diet, physical activity, and alcohol intake had a lower risk of mortality than former smokers who didn't adhere to these recommendations.”
A medication for heart problems and high blood pressure may also be effective for treating alcohol use disorder, according to a new study by researchers at the National Institutes of Health and their colleagues. The study presents converging evidence from experiments in mice and rats, as well as a cohort study in humans, suggesting that the medication, spironolactone, may play a role in reducing alcohol drinking. The research was led by scientists at the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both parts NIH, and Yale School of Medicine, New Haven, Connecticut. A report of the new findings is published in Molecular Psychiatry.
“Combining findings across three species and different types of research studies, and then seeing similarities in those data, gives us confidence that we are onto something potentially important scientifically and clinically. These findings support further study of spironolactone as a potential treatment for alcohol use disorder, a medical condition that affects millions of people in the U.S.,” said Lorenzo Leggio, M.D., Ph.D., chief of the Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, a joint laboratory of NIDA and NIAAA, and one of the senior authors.
Currently there are three medications approved for alcohol use disorder in the United States, and they are an effective and important aid in the treatment of people with this condition. Given the diverse biological processes that contribute to alcohol use disorder, new medications are needed to provide a broader spectrum of treatment options. Scientists are working to develop a larger menu of pharmaceutical treatments that could be tailored to individual needs.
