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:
The act of cooking offers the chance to unwind and create something special, whether you’re planning to feed a crowd or just yourself. And while you may have noticed feeling good after whipping up that perfect pie or braise, there’s actually a lot of scientific data to suggest that cooking can have a positive impact on mental health.
One meta-analysis (external link) (a report of pre-existing research) from the National Institutes of Health looked at 11 studies and found that “cooking interventions” — encouraging people to follow certain recipes or giving people cooking classes — can improve a person’s mental well-being. It specifically found that people who participated in cooking interventions reported having better self-esteem and quality of life, as well as a more positive emotional state after the fact. Another study even discovered that baking can help raise a person’s confidence level.
An experimental form of immunotherapy that uses an individual’s own tumor-fighting immune cells could potentially be used to treat people with metastatic breast cancer, according to results from an ongoing clinical trial led by researchers at the National Cancer Institute’s (NCI) Center for Cancer Research, part of the National Institutes of Health. Many people with metastatic breast cancer can mount an immune reaction against their tumors, the study found, a prerequisite for this type of immunotherapy, which relies on what are called tumor-infiltrating lymphocytes (TILs).
In a clinical trial of 42 women with metastatic breast cancer, 28 (or 67%) generated an immune reaction against their cancer. The approach was used to treat six women, half of whom experienced measurable tumor shrinkage. Results from the trial appeared Feb. 1, 2022, in the Journal of Clinical Oncology.
“It’s popular dogma that hormone receptor–positive breast cancers are not capable of provoking an immune response and are not susceptible to immunotherapy,” said study leader Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI’s Center for Cancer Research. “The findings suggest that this form of immunotherapy can be used to treat some people with metastatic breast cancer who have exhausted all other treatment options.”
Before TIL therapy, a woman with breast cancer had metastatic lesions in her chest wall (top, left) and liver (bottom, left). After receiving the immunotherapy, her tumors shrank completely, and recent scans (right) show that she remains cancer free more than five years later.
Research sheds light on severity for gene variants; establishes outcome measures for therapeutic trials
National Eye Institute researchers developed and validated an artificial-intelligence-based method to evaluate patients with Stargardt, an eye disease that can lead to childhood vision loss. The method quantifies disease-related loss of light-sensing retina cells, yielding information for monitoring patients, understanding genetic causes of the disease, and developing therapies to treat it. The findings published today in JCI Insight.
“These results provide a framework to evaluate Stargardt disease progression, which will help control for the significant variability from patient to patient and facilitate therapeutic trials,” said Michael F. Chiang, M.D. (external link), director of the NEI, which is part of the National Institutes of Health.
About 1 in 9,000 people develop the most common form of Stargardt, or ABCA4-associated retinopathy, an autosomal-recessive disease caused by variants to the ABCA4 gene, which contains genetic information for a transmembrane protein in light-sensing photoreceptor cells. People develop Stargardt when they inherit two mutated copies of ABCA4, one from each parent. People who have just one mutated copy of ABCA4 are genetic carriers, but do not develop the disease. More rare forms of Stargardt are associated with variants of other genes.
Spectral-domain optical coherence tomography uses light to image layers of the retina. Many scans taken over five years were analyzed using deep learning, a type of artificial intelligence in which imaging data are fed into an algorithm that learns how to detect patterns. Six retinal layers were segmented and analyzed for changes in thickness.
Small NIH study contributes to understanding of COVID-19 during pregnancy
SARS-CoV-2 infection during pregnancy may cause inflammatory immune responses in the fetus, even if the virus does not infect the placenta, according to a small National Institutes of Health study. Researchers describe unique maternal, fetal, and placental immune responses among pregnant women with COVID-19 in a study led by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The findings detail changes in antibodies, immune cell types and inflammatory markers in maternal blood, umbilical cord blood and placental tissues. The study is published in the journal Nature Communications.
People who are pregnant are at a higher risk for severe illness from COVID-19, compared to people who are not pregnant. COVID-19 during pregnancy also increases the risk for preterm birth, stillbirth and preeclampsia. Therefore, understanding COVID-19 infection during pregnancy is important to help healthcare providers optimize the health and safety of their patients during the pandemic.
The study evaluated 23 pregnant women. Twelve were positive for SARS-CoV-2, and of these, eight were asymptomatic, one had mild symptoms and three had severe COVID-19. After delivery, the researchers compared immune responses between mothers and their newborns by comparing maternal blood and umbilical cord blood. Inflammatory immune responses triggered by the virus were observed in women, their neonates and placental tissues regardless of whether the mothers had symptoms.
Use of patient-derived stem cells will enable high-throughput drug screening for potential therapeutics
Researchers at the National Eye Institute (NEI) have developed the first patient-derived stem cell model for studying eye conditions related to oculocutaneous albinism (OCA). The model’s development is described in the January issue of the journal Stem Cell Reports. NEI is part of the National Institutes of Health.
“This ‘disease-in-a-dish’ system will help us understand how the absence of pigment in albinism leads to abnormal development of the retina, optic nerve fibers, and other eye structures crucial for central vision,” said Aman George, Ph.D., a staff scientist in the NEI Ophthalmic Genetics and Visual Function Branch (external link), and the lead author of the report.
OCA is a set of genetic conditions that affects pigmentation in the eye, skin, and hair due to mutation in the genes crucial to melanin pigment production. In the eye, pigment is present in the retinal pigment epithelium (RPE), and aids vision by preventing the scattering of light. The RPE is located right next to the eye’s light-sensing photoreceptors and provides them nourishment and support. People with OCA lack pigmented RPE and have an underdeveloped fovea, an area within the retina that is crucial for central vision. The optic nerve carries visual signals to the brain.
A human induced pluripotent stem cell colony from OCA1A patient. The image was acquired using a confocal microscope and is stained for pluripotency marker proteins. The red color depicts transcription factor OCT4, green is SSEA4 protein, and blue represents the nucleus of the cells.
A diet rich in fiber may help some people being treated for melanoma respond to immunotherapy treatment by influencing the gut microbiome, according to a new study led by researchers at the Center for Cancer Research at the National Cancer Institute (NCI), part of the National Institutes of Health, and the University of Texas MD Anderson Cancer Center. Results from the study, which analyzed both people with melanoma and mouse models of the disease, appear in Science.
Among patients with advanced melanoma who underwent immunotherapy with immune checkpoint blockers, those who consumed at least 20 grams a day of dietary fiber survived the longest without their disease progressing. In contrast, use of probiotic supplements appeared to lessen somewhat the effectiveness of immune checkpoint blocker regimens. Probiotics are live microorganisms typically consumed as a supplement to improve gut health.
“The data suggest that one can target the composition of the gut microbiota and affect the ability of the patient to respond to immunotherapy,” said Giorgio Trinchieri, M.D., chief of the Laboratory of Integrative Cancer Immunology in NCI’s Center for Cancer Research, one of the study’s coleaders. “Consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy.”
Human and animal study offers insight into treating periodontal disease and other inflammatory disorders
Blocking function of a blood-clotting protein prevented bone loss from periodontal (gum) disease in mice, according to research led by scientists at the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health. Drawing on animal and human data, the researchers found that buildup of the protein, called fibrin, triggers an overactive immune response that damages the gums and underlying bone. The study, which was published in Science, suggests that suppressing abnormal fibrin activity could hold promise for preventing or treating periodontal disease, as well as other inflammatory disorders marked by fibrin buildup, including arthritis and multiple sclerosis.
Periodontal disease affects nearly half of Americans over age 30, and 70% of those 65 and older. It is a bacterial infection of the tissues supporting the teeth. In its early stages, periodontal disease causes redness and swelling (inflammation) of the gums. In advanced stages, called periodontitis, the underlying bone becomes damaged, leading to tooth loss. While scientists have known that periodontitis is driven in part by an exaggerated immune cell response, until now, it was unclear what triggered the response, and how it caused tissue and bone damage.
”Severe periodontal disease can lead to tooth loss and remains a barrier to productivity and quality of life for far too many Americans, especially those lacking adequate access to dental care,” said NIDCR Director Rena D’Souza, D.D.S., Ph.D. (external link) “By providing the most comprehensive picture yet of the underlying mechanisms of periodontal disease, this study brings us closer to more effective methods for prevention and treatment.”
Model replicates features of complex disease, provides platform for screening existing drugs
Using a stem-cell-derived model, researchers have identified two drug candidates that may slow dry age-related macular degeneration (AMD), a leading cause of blindness for which no treatment exists. The scientists, from the National Eye Institute (NEI), part of the National Institutes of Health, published their findings today in Nature Communications.
“This stem-cell-derived model of dry AMD is a game-changer. Scientists have struggled to unravel this incredibly complex disease, and this model could prove to be invaluable for understanding the causes of AMD and discovering new therapies,” said Michael F. Chiang M.D. (external link), director of the NEI.
This is among the first studies to show that it’s possible to develop a dish-based model that replicates the characteristics (phenotype) of a complex disease, as opposed to a disease caused by a single mutation. The causes of AMD involve a yet-to-be-understood combination of genetic factors, aging, and behavior-related risk factors such as smoking and diet.
Pregnant women with disabilities have a much higher risk for severe pregnancy- and birth-related complications and death than other pregnant women, according to findings by researchers at the National Institutes of Health. Appearing in JAMA Network Open, the analysis of more than 223,000 deliveries in 19 U.S. hospitals found that roughly 2,199 women had a disability.
An experimental HIV vaccine based on mRNA—the same platform technology used in two highly effective COVID-19 vaccines—shows promise in mice and non-human primates, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Their results, published in Nature Medicine, show that the novel vaccine was safe and prompted desired antibody and cellular immune responses against an HIV-like virus. Rhesus macaques receiving a priming vaccine followed by multiple booster inoculations had a 79% lower per-exposure risk of infection by simian-human immunodeficiency virus (SHIV) compared to unvaccinated animals. The research was led by Paolo Lusso, M.D., Ph.D., of NIAID’s Laboratory of Immunoregulation, in collaboration with other NIAID scientists, investigators from Moderna, Inc. and colleagues at other institutions.
“Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains an elusive goal,” said NIAID Director Anthony S. Fauci, M.D., chief of the Laboratory and a paper co-author. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.”
The experimental vaccine works like mRNA COVID-19 vaccines. However, instead of carrying mRNA instructions for the coronavirus spike protein, the vaccine delivers coded instructions for making two key HIV proteins, Env and Gag. Muscle cells in an inoculated animal assemble these two proteins to produce virus-like particles (VLPs) studded with numerous copies of Env on their surface. Although they cannot cause infection or disease because they lack the complete genetic code of HIV, these VLPs match whole, infectious HIV in terms of stimulating suitable immune responses.
Scientists have discovered that gene therapy and the diabetes drug metformin may be potential treatments for late-onset retinal degeneration (L-ORD), a rare, blinding eye disease. Researchers from the National Eye Institute (NEI), part of the National Institutes of Health, generated a “disease-in-a-dish” model to study the disease. The findings are published in Communications Biology.
“This new model of a rare eye disease is a terrific example of translational research, where collaboration among clinical and laboratory researchers advances knowledge not by small steps, but by leaps and bounds,” said Michael F. Chiang, M.D. (external link), director of the NEI, part of the National Institutes of Health.
L-ORD is a rare, dominantly inherited disorder, meaning that it can occur when there is an abnormal gene from one parent. L-ORD is caused by a mutation in the gene that encodes the protein CTRP5. People with the disorder develop abnormal blood vessel growth and deposits of apolipoprotein E, which is involved in fat metabolism within the retina. Symptoms, including difficulty seeing in the dark and loss of central vision, usually appear around age 50 to 60. As L-ORD progresses, cells in the retinal pigment epithelium (RPE), a layer of tissue that nourishes the retina’s light-sensing photoreceptors, shrink and die. Loss of RPE leads to the loss of photoreceptors and in turn, to loss of vision.