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:
Whether you’re shedding pounds with the help of effective new medicines, slimming down after weight loss surgery or cutting calories and adding exercise, there will come a day when the numbers on the scale stop going down, and you hit the dreaded weight loss plateau.
In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, looked at when weight loss typically stops depending on the method people were using todrop pounds. He broke down the plateau into mathematical models using data from high-quality clinical trials of different ways to lose weight to understand why people stop losing when they do. The study published Monday in the journal Obesity.
After 10 years, AREDS2 formula shows increased efficacy compared to original formula, benefit of eliminating beta-carotene
The Age-Related Eye Disease Studies (AREDS and AREDS2) established that dietary supplements can slow progression of age-related macular degeneration (AMD), the most common cause of blindness in older Americans. In a new report, scientists analyzed 10 years of AREDS2 data. They show that the AREDS2 formula, which substituted antioxidants lutein and zeaxanthin for beta-carotene, not only reduces risk of lung cancer due to beta-carotene, but is also more effective at reducing risk of AMD progression, compared to the original formula. A report on the study, funded by the National Institutes of Health, published in JAMA Ophthalmology.
“Because beta-carotene increased the risk of lung cancer for current smokers in two NIH-supported studies, our goal with AREDS2 was to create an equally effective supplement formula that could be used by anyone, whether or not they smoke,” said Emily Chew, M.D., director of the Division of Epidemiology and Clinical Application at the National Eye Institute (NEI), and lead author of the study report. “This 10-year data confirms that not only is the new formula safer, it’s actually better at slowing AMD progression.”
AMD is a degenerative disease of the retina, the light-sensitive tissue at the back of the eye. Progressive death of retinal cells in the macula, the part of the retina that provides clear central vision, eventually leads to blindness. Treatment can slow or reverse vision loss; however, no cure for AMD exists.
Individuals with HIV who began taking antiretroviral therapy (ART) in the early stages of infection achieved a lengthy period of HIV suppression without ART after receiving two broadly neutralizing anti-HIV antibodies (bNAbs), according to a small study published today in the journal Nature. The findings suggest that combination bNAb therapy might offer a future alternative to daily ART for people living with HIV. The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in collaboration with researchers at the NIH Clinical Center; the Maple Leaf Medical Clinic in Toronto; the Frederick National Laboratory for Cancer Research; Harvard Medical School, Boston; and The Rockefeller University, New York City.
Although oral antiretrovirals are highly effective at keeping HIV levels under control, it can be difficult for some people with HIV to adhere to a daily medication regimen. Additionally, the medicines can present long-term side effects from lifetime usage and create the possibility for the development of drug-resistant virus. In previous research, single bNAbs showed only limited success in keeping virus levels low partly because bNAb-resistant HIV either already existed or emerged in the individual. To address this problem, researchers in the NIAID Laboratory of Immunoregulation tested a dual combination of bNAbs — called 3BNC117 and 10-1074 — targeting different parts of the surface of HIV.
The researchers conducted a two-component clinical trial between September 2018 and January 2021. The first component was a Phase 1 randomized, placebo-controlled trial involving 14 participants with HIV. These individuals had started ART during the early phase of their infection. They were taken off antiretrovirals shortly after receiving their first infusion of the combination bNAbs or placebo. Participants received up to eight bNAb or placebo infusions — two in the first month and once monthly thereafter — for 24 weeks. HIV levels and CD4 T-cell counts were measured every two weeks.
Scanning electron micrograph of an HIV-infected H9 T cell, colorized in Halloween colors.
From 1999 to 2019, rates of cancer deaths declined steadily among Black people in the United States. Nevertheless, in 2019, Black people still had considerably higher rates of cancer death than people in other racial and ethnic groups, a large epidemiologic study has found. The study was led by researchers at the National Cancer Institute, part of the National Institutes of Health, and the findings appeared May 19 in JAMA Oncology.
“Even though there has been a decline in cancer mortality nationally among Black people, they continued to bear a higher cancer burden overall than all other racial and ethnic groups studied,” said Wayne R. Lawrence, Dr.P.H., of the Metabolic Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics, who led the study.
Dr. Lawrence and his colleagues used death certificate data from the National Center for Health Statistics to analyze age-adjusted cancer death rates by age, sex, and cancer site among non-Hispanic Black people ages 20 and older in the United States. They then compared cancer death rates in 2019 among Black men and women with those in other racial and ethnic groups.
NIH findings could lead to ways to combat future SARS-CoV-2 variants
Unlike other SARS-CoV-2 variants, the Delta variant can attach to copies of itself, forming larger aggregations, or clumps, of viral particles, suggests a study by scientists at the National Institutes of Health. The researchers theorize that this linking property may have played a role in the ability of the Delta variant to spread more rapidly than all the variants that preceded it.
The Delta spike protein enables the virus to bind to cells and begin the process of infecting them. In laboratory studies, the researchers observed this action by using leukemia viruses from mice that were stripped of disease-causing genes but engineered to have the spike protein on their surface, known as pseudotyped Delta particles. The scientists watched the spike proteins binding to one another to form aggregations, which previous research suggests increases the chances of viral spread.
Viruses deep inside the aggregation are protected from drying out, from antiviral drugs and from the host immune system. Moreover, large viral aggregations have the potential to a bring a greater number of viruses in contact with target cells, thereby increasing the chances of infection. The authors note that future studies are needed to confirm whether the SARS-CoV-2 Delta variant can form aggregations similar to those of the Delta pseudo particles.
Electron microscopy image of an aggregate of pseudotyped viral particles bearing the SARS-CoV-2 Delta variant spike protein.
NIH discovery sheds light on tissue targeted by age-related macular degeneration and other diseases
Researchers have identified distinct differences among the cells comprising a tissue in the retina that is vital to human visual perception. The scientists from the National Eye Institute (NEI) discovered five subpopulations of retinal pigment epithelium (RPE) — a layer of tissue that nourishes and supports the retina’s light-sensing photoreceptors. Using artificial intelligence, the researchers analyzed images of RPE at single-cell resolution to create a reference map that locates each subpopulation within the eye. A report on the research published in Proceedings of the National Academy of Sciences.
“These results provide a first-of-its-kind framework for understanding different RPE cell subpopulations and their vulnerability to retinal diseases, and for developing targeted therapies to treat them,” said Michael F. Chiang, M.D., director of the NEI, part of the National Institutes of Health.
“The findings will help us develop more precise cell and gene therapies for specific degenerative eye diseases,” said the study’s lead investigator, Kapil Bharti, Ph.D., who directs the NEI Ocular and Stem Cell Translational Research Section.
Five subpopulations of RPE (P1-P5) were identified based on cell area, aspect ratio, hexagonality and number of neighbors. Foveal RPE (P1) are tightly packed hexagons. Peripheral RPE (P5) are spread out.
Deaths from uterine cancer are rising in the United States, and are highest among non-Hispanic Black women, according to a new study led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The higher death rates are related to the rising incidence of aggressive subtypes of uterine cancer.The researchers found that, from 2010 to 2017, deaths of women from all racial and ethnic groups from uterine cancer overall increased 1.8% per year. Deaths from non-endometroid subtypes of uterine cancer—which are more aggressive than endometrioid cancers—increased by 2.7% per year, whereas endometrioid cancer mortality rates were stable during this period. Black women had more than twice the rate of deaths from uterine cancer overall and of non-endometrioid subtypes compared to other racial and ethnic groups.
Despite decline, smoking cessation efforts still critical for people with substance use or other psychiatric disorders
Significant reductions in cigarette use were found among U.S. adults with major depression, substance use disorder, or both from 2006 to 2019, according to a new analysis of nationally representative survey data published today in JAMA. The study was conducted by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the Substance Abuse and Mental Health Services Administration (SAMHSA). These findings suggest that groups at higher risk of cigarette smoking can be reached by, and may have benefitted from, tobacco use prevention and cessation efforts that have led to significant declines in tobacco use in the general population. At the same time, the findings highlight remaining disparities, documenting higher smoking rates in people with psychiatric disorders than in those without.
“This study shows us that, at a population-level, reductions in tobacco use are achievable for people with psychiatric conditions, and smoking cessation should be prioritized along with treatments for substance use, depression, and other mental health disorders for people who experience them,” said Nora Volkow, M.D., director of NIDA and co-author of the study. “Therapies to help people stop smoking are safe, effective, and may even enhance the long-term success of concurrent treatments for more severe mental health symptoms in individuals with psychiatric disorders by lowering stress, anxiety, depression, and by improving overall mood and quality of life.”
The study enrolled approximately 5,000 mothers and 6,000 children born between 2008 and 2010. Mothers responded periodically to questionnaires on their health and their children’s health and medical histories. Infertility treatments included in vitro fertilization (sperm and egg are combined in a laboratory dish and inserted in the uterus), drugs that stimulate ovulation, and a procedure in which sperm are inserted into the uterus.
Compared to children conceived without infertility treatment, children conceived after treatment were more likely to have persistent wheeze by age 3, a potential indication of asthma. At 7 to 9 years old, children conceived with treatment were 30% more likely to have asthma, 77% more likely to have eczema (an allergic condition resulting in rashes and itchy skin) and 45% more likely to have a prescription for an allergy medication.
New findings from the ongoing Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study suggest that certain rheumatoid arthritis drugs may lower incidence of Alzheimer’s disease and related dementias in people with cardiovascular disease. While the findings do not support broad use of these drugs for treating Alzheimer’s and related dementias, the results may point to a promising precision-medicine approach in specific groups of people at risk for developing these diseases. The research was published in JAMA Network Open and led by scientists at the National Institutes of Health’s National Institute on Aging in collaboration with researchers at Harvard Medical School, Boston; Rutgers University, New Brunswick, New Jersey; and Johns Hopkins University School of Medicine, Baltimore.
Discovering new drug targets in Alzheimer’s and related dementias is crucial for meeting the enormous public health challenge of these diseases. Prior studies on whether approved rheumatoid arthritis drugs lower the risk of developing dementia have produced mixed results. In this study, researchers analyzed data in Medicare claims from more than 22,000 people, looking at whether those with rheumatoid arthritis who took one of three different classes of arthritis drugs were protected from dementia. There were no statistically significant associations with lowered dementia risk except among those with cardiovascular disease who were treated with one class of arthritis drugs called TNF inhibitors. These inhibitors suppress the immune system by blocking the activity of TNF, which is a substance in the body that can cause inflammation and lead to immune-system diseases, including rheumatoid arthritis.
Norman E. “Ned” Sharpless, M.D., announced today that he has decided to step down from his position as director of the National Cancer Institute (NCI), part of the National Institutes of Health, a position he has held since 2017. Dr. Sharpless will continue as NCI director through April 29, 2022, to allow for a thorough transition. NCI Principal Deputy Director Douglas R. Lowy, M.D., will serve as NCI’s acting director effective April 30, 2022.
“Working at the National Cancer Institute has been the highlight of my career, and I am honored to have had the chance to serve my country in this role, alongside so many talented scientists and administrators,” Dr. Sharpless said. “I leave this job knowing that the talent and passion present at NCI, across the Biden-Harris Administration and throughout the cancer research community will continue to fuel tremendous progress for people with cancer in the years ahead.”
Dr. Sharpless was sworn in as the 15th director of NCI on Oct. 17, 2017. He also served as Acting Commissioner for Food and Drugs at the U.S. Food and Drug Administration (FDA) for seven months in 2019, before returning to the NCI directorship.
National Cancer Institute Director Norman E. “Ned” Sharpless, M.D.
