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.
A class of viruses known to cause severe diarrheal diseases — including the one famous for widespread outbreaks on cruise ships — can grow in the salivary glands of mice and spread through their saliva, scientists at the National Institutes of Health have discovered. The findings show that a new route of transmission exists for these common viruses, which afflict billions of people each year worldwide and can be deadly.
The transmission of these so-called enteric viruses through saliva suggests that coughing, talking, sneezing, sharing food and utensils, and even kissing all have the potential for spreading the viruses. The new findings still need to be confirmed in human studies.
The findings, which appear in the journal Nature, could lead to better ways to prevent, diagnose, and treat diseases caused by these viruses, potentially saving lives. The study was led by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.
A microscopic view of salivary gland acinar epithelial cells (pink) infected with rotavirus (green), a type of enteric virus, in a mouse.
Discovery may represent a future target for treating substance use disorders
Researchers have found that blocking certain acetylcholine receptors in the lateral habenula (LHb), an area of the brain that balances reward and aversion, made it harder to resist seeking cocaine in a rat model of impulsive behavior. These findings identify a new role for these receptors that may represent a future target for the development of treatments for cocaine use disorder. There are currently no approved medications to treat cocaine use disorder.
Published in the Journal of Neuroscience, the study was supported by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health. In 2020, over 41,000 people died from drug overdoses involving stimulants, including cocaine and methamphetamine. Developing safe and effective medications that help treat addictions to cocaine and other stimulants is critical to expand the choices offered to people seeking treatment and to help sustain recovery.
“The LHb acts like an interface between rational thought in the forebrain and the modulation of neurotransmitters like dopamine and serotonin that originate in the midbrain, which are important in regulating decision processes and emotions,” said Carl Lupica, Ph.D., chief of the Electrophysiology Research Section of the Computational and Systems Neuroscience Branch of NIDA. “While the immediate results of this study are related to cocaine seeking, there are also greater implications for impulsivity as it relates to other drugs as well as to psychiatric conditions like obsessive-compulsive disorder. Our future studies will explore the relationship between LHb activity and impulsive behavior related to other drugs such as cannabis, and opioids such as heroin.”
County-level data provides unprecedented detail by geography and population groups
From 2000-2019 overall life expectancy in the United States increased by 2.3 years, but the increase was not consistent among racial and ethnic groups and by geographic area. In addition, most of these gains were prior to 2010. This is according to a new study funded by the National Institutes of Health that examined trends in life expectancy at the county level. The study was led by researchers at the Institute for Health Metrics and Evaluation at the University of Washington’s School of Medicine, Seattle, in collaboration with researchers from NIH and published on June 16th in The Lancet.
“These varied outcomes in life expectancy raise significant questions. Why is life expectancy worse for some and better for others? The novel details in this study provide us the opportunity to evaluate the impact of social and structural determinants on health outcomes in unprecedented ways. This in turn allows us to better identify responsive and enduring interventions for local communities,” said Eliseo J. Pérez-Stable, M.D., co-author and director of the National Institute on Minority Health and Health Disparities (NIMHD), part of NIH.
In most counties, life expectancy for the Black population has increased more than any other racial and ethnic group but overall, the Black population still has a lower life expectancy than the white population. Meanwhile, the white population had a moderate increase, and in some counties, a decrease in life expectancy. Considering these two trends, the study noted that the decrease in the white-Black life expectancy gap could be attributed to the stagnation and reversal of gains in the white population. In addition, American Indian and Alaska Native populations have the lowest life expectancy of all populations and experienced a decrease in most counties, with a gap of more than 21 years in some counties.
Genetic and clinical research reveals new type of macular dystrophy, a cause of central vision loss
Researchers from the National Eye Institute (NEI) have identified a new disease that affects the macula, a small part of the light-sensing retina needed for sharp, central vision. Scientists report their findings on the novel macular dystrophy, which is yet to be named, in JAMA Ophthalmology. NEI is part of the National Institutes of Health.
Macular dystrophies are disorders that usually cause central visual loss because of mutations in several genes, including ABCA4, BEST1, PRPH2, and TIMP3.
For example, patients with Sorsby Fundus Dystrophy, a genetic eye disease specifically linked to TIMP3 variants, usually develop symptoms in adulthood. They often have sudden changes in visual acuity due to choroidal neovascularization– new, abnormal blood vessels that grow under the retina, leaking fluid and affecting vision.
TIMP3 is a protein that helps regulate retinal blood flow and is secreted from the retinal pigment epithelium (RPE), a layer of tissue that nourishes and supports the retina’s light-sensing photoreceptors. All TIMP3 gene mutations reported are in the mature protein after it has been “cut” from RPE cells in a process called cleavage.
“We found it surprising that two patients had TIMP3 variants not in the mature protein, but in the short signal sequence the gene uses to ‘cut’ the protein from the cells. We showed these variants prevent cleavage, causing the protein to be stuck in the cell, likely leading to retinal pigment epithelium toxicity,” said Bin Guan, Ph.D., lead author.
Retinal images of a patient with a TIMP3 mutation causing atypical symptoms. While there is visible damage in the retina (dark circles), there is no CNV present.
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.
