Tuesday, February 18, 2020
Findings suggest drugs targeting immune cells may help treat deadly disease mainly affecting children
Researchers at the National Institutes of Health found evidence that specific immune cells may play a key role in the devastating effects of cerebral malaria, a severe form of malaria that mainly affects young children. The results, published in the Journal of Clinical Investigation, suggest that drugs targeting T cells may be effective in treating the disease. The study was supported by the NIH Intramural Research Program.
“This is the first study showing that T cells target blood vessels in brains of children with cerebral malaria,” said Dorian McGavern, Ph.D., chief of the Viral Immunology and Intravital Imaging Section at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) who co-directed the study with Susan Pierce, Ph.D., chief of the Laboratory of Immunogenetics at the National Institute of Allergy and Infectious Diseases (NIAID). “These findings build a bridge between mouse and human cerebral malaria studies by implicating T cells in the development of disease pathology in children. It is well established that T cells cause the brain vasculature injury associated with cerebral malaria in mice, but this was not known in humans.”
More than 200 million people worldwide are infected annually with mosquito-borne parasites that cause malaria. In a subset of those patients, mainly young children, the parasites accumulate in brain blood vessels causing cerebral malaria, which leads to increased brain pressure from swelling. Even with available treatment, cerebral malaria still kills up to 25% of those affected resulting in nearly 400,000 deaths annually. Children who survive the infection will often have long-lasting neurological problems such as cognitive impairment.
Specific immune cells accumulate within brain blood vessels of people affected by cerebral malaria. This finding suggests a new treatment strategy for the disease.
Thursday, February 13, 2020
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions. The findings provide insight into the genetic factors underlying the risk of type 2 diabetes and may inform strategies for reducing this risk among women who had gestational diabetes.
The study was conducted by Mengying Li, Ph.D., of the Division of Intramural Population Health Research at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and colleagues. It appears in BMJ Open Diabetes Research & Care.
“Our study suggests that a healthful diet may reduce risk among women who have had gestational diabetes and are genetically susceptible to type 2 diabetes,” said the study’s senior author Cuilin Zhang, M.D., Ph.D., of NICHD’s Division of Intramural Population Health Research. “However, larger studies are needed to validate these findings.”
Thursday, February 13, 2020
Results support testing antiviral against 2019 novel coronavirus
The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.
The new report from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.
MERS-CoV is closely related to the 2019 novel coronavirus (2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.
Colorized scanning electron micrograph of Marburg virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (yellow). Image captured and color-enhanced at the NIAID Integrated Research Facility in Fort Detrick, Maryland.
Thursday, February 13, 2020
NIH-supported research of Hydractinia could provide clues to human reproductive conditions
A little-known ocean-dwelling creature most commonly found growing on dead hermit crab shells may sound like an unlikely study subject for researchers, but this animal has a rare ability — it can make eggs and sperm for the duration of its lifetime. This animal, called Hydractinia, does so because it produces germ cells, which are precursors to eggs and sperm, nonstop throughout its life. Studying this unique ability could provide insight into the development of human reproductive system and the formation of reproductive-based conditions and diseases in humans.
“By sequencing and studying the genomes of simpler organisms that are easier to manipulate in the lab, we have been able to tease out important insights regarding the biology underlying germ cell fate determination — knowledge that may ultimately help us better understand the processes underlying reproductive disorders in humans,” Dr. Andy Baxevanis, director of the National Human Genome Research Institute’s (NHGRI) Computational Genomics Unit and co-author of the paper. NHGRI is part of the National Institutes of Health.
In a study published in the journal Science, collaborators at NHGRI, the National University of Ireland, Galway, and the Whitney Laboratory for Marine Bioscience at the University of Florida, Augustine, reported that activation of the gene Tfap2 in adult stem cells in Hydractinia can turn those cells into germ cells in a cycle that can repeat endlessly.
Timing of germ cell formation in Hydractinia versus most animals. Image credit: NHGRI
Monday, February 10, 2020
Gene modifications correspond to blood pressure increases at distinct pregnancy intervals
Higher maternal blood pressure in pregnancy is associated with chemical modifications to placental genes, according to a study by researchers from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH). The changes involve DNA methylation, the binding of compounds known as methyl groups to DNA, which can alter a gene’s activity. Exposure to high blood pressure in the womb increases the risk for impaired fetal growth and the risk for cardiovascular disease in adult life. Ultimately, the findings could yield information on the earliest origins of cardiovascular disease and how to prevent it from occurring.
The researchers conducted a comprehensive genetic analysis, called an epigenome-wide association study (EWAS), on biopsies of placentas delivered from 301 pregnant women in the NICHD Fetal Growth Study. EWAS detects DNA methylation and other changes to gene functioning. The authors believe their study is the first EWAS to compare placental DNA methylation to maternal blood pressure across trimesters. The study team found distinct patterns of DNA methylation in the placental tissue, which corresponded with the timing of blood pressure elevations in pregnancy. Many of the methylated genes were found in earlier studies to be involved in cardiovascular functioning.
The researchers hope to study patterns of DNA methylation in larger groups of pregnant women, including those with pregnancy-associated blood pressure disorders such as preeclampsia.
Monday, January 27, 2020
NIH trial will test NIAID-developed antibody
A Phase 1 clinical trial testing the safety and effectiveness of a monoclonal antibody (mAb) against malaria has begun enrolling healthy adult volunteers at the National Institutes of Health Clinical Center in Bethesda, Maryland. The trial, sponsored by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), is the first to test mAb CIS43LS in humans. It aims to enroll up to 73 volunteers aged 18 through 50 years old who have never had malaria. After receiving mAb CIS43LS, most of the volunteers will be exposed to malaria parasite-carrying mosquitoes under carefully controlled conditions at the Walter Reed National Military Medical Center in Bethesda to assess the ability of the mAb to confer protection from malaria infection.
“If proven safe and effective in this study and in larger trials, this monoclonal antibody might be used prophylactically by tourists, medical workers or military personnel who travel to areas where malaria is common,” said NIAID Director Anthony S. Fauci, M.D. “In the absence of a highly effective, long-lasting vaccine, preventing malaria infections for several months with a single dose of monoclonal antibody also could be valuable in specific parts of Africa where malaria cases increase greatly during annual rainy seasons,” he added.
Several years ago, Robert Seder, M.D., and colleagues at NIAID’s Vaccine Research Center (VRC) isolated an antibody (CIS43) from the blood of a volunteer who had received an investigational vaccine made from whole, weakened malaria parasites. When tested in two different mouse models of malaria infection, CIS43 was highly effective at preventing infection by the deadliest malaria parasite, Plasmodium falciparum, the team reported in 2018. Modifications to CIS43 yielded mAb CIS43LS, which lasts longer in the blood than the original antibody. CIS43LS was manufactured for clinical use by the VRC’s investigational product Vaccine Production Program and the NIAID-funded Vaccine Clinical Material Program of Leidos Biomedical Research, Inc., under a contract to the National Cancer Institute’s Frederick National Laboratory for Cancer Research.
NIAID Research Nurse Jennifer Cunningham, B.S.N., looks on as a healthy volunteer receives an infusion of CIS43LS, an experimental monoclonal antibody against malaria, as part of a Phase 1 clinical trial.
Tuesday, January 21, 2020
A National Institutes of Health study found that chronic treatment with mirabegron, a drug approved to treat overactive bladder, activated brown fat in a small group of healthy women and had several other beneficial metabolic effects. Brown fat, or brown adipose tissue, is a form of fat that burns calories to generate heat. The research, led by Aaron Cypess, M.D., Ph.D., at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was published on Jan. 21 in the Journal of Clinical Investigation.
Fourteen women aged 18-40 of diverse ethnicities participated in the study at the NIH Clinical Center’s Metabolic Clinical Research Unit. For four weeks, each participant received daily doses of 100 mg of mirabegron, an amount exceeding the 50 mg maximum dosage approved by the U.S. Food and Drug Administration.
At four weeks, the participants’ brown fat activity had more than doubled since the first day, though their body weight and body mass stayed the same. Other changes included:
- Increased resting energy expenditure
- Higher levels of HDL (high-density lipoprotein) cholesterol — often referred to as “good” cholesterol — and bile acids, which help digest fats and regulate cholesterol
- Improved processing and regulation of blood glucose (blood sugar)
Human brown adipose tissue, or brown fat.
Photo courtesy of the Journal of Clinical Investigation
Thursday, January 16, 2020
NIH study shows treatment recommendations impacted by patient and physician factors
During their first physician visit, patients experiencing newly diagnosed chronic musculoskeletal pain are prescribed opioids more often than physical therapy, counseling, and other nonpharmacologic approaches, according to a new study published in the Journal of Pain. The use of opioids over other approaches stands in contrast with clinical recommendations for the use of nonopioid pain approaches and nonpharmacologic approaches. The study included authors from the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health; the University of Montreal; and McMaster University in Hamilton, Ontario, Canada.
“Particularly when the patient is experiencing pain that may become chronic, that first clinical encounter can set the course for patient care moving forward,” said Helene Langevin, M.D., director of NCCIH. “This study was designed to assess the ways in which real-world practice compares and contrasts with practice guidelines for these initial patient encounters.”
Study authors analyzed data from the National Ambulatory Medical Care Survey (NAMCS), conducted between 2007 and 2015. The survey data are collected by the Centers for Disease Control and Prevention’s National Center for Health Statistics and represent how medical care services are used in the United States. The results concur with the high prevalence of chronic musculoskeletal pain in the United States, with an average of 36.8 million initial visits (for a new chronic pain problem) per year or approximately 11.8% of the population.
Tuesday, January 7, 2020
Dietary supplements containing zinc and folic acid — marketed as a treatment for male infertility — do not appear to improve pregnancy rates, sperm counts or sperm function, according to a study conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health. The study appears in the Journal of the American Medical Association.
The authors note that most so-called fertility supplements contain zinc and folic acid. Zinc is an essential mineral for sperm formation, and folate, the natural form of folic acid, depends on zinc to help form DNA in the sperm. Previous studies of these nutrients as a treatment for male infertility have produced conflicting results.
“Our study is one of the first randomized, placebo-controlled trials to assess whether folic acid and zinc supplements help to improve male fertility,” said Enrique Schisterman, Ph.D., of the NICHD Division of Intramural Population Health Research, who conducted the trial, along with colleagues. “Our results suggest that these dietary supplements have little to no effect on fertility and may even cause mild gastrointestinal symptoms.”
Thursday, January 2, 2020
Tuberculosis (TB), an ancient disease, is the leading infectious cause of death globally, yet the world’s only licensed TB vaccine, Bacille Calmette-Guerin (BCG), was developed a century ago. Given to infants via a needle placed just under the skin, BCG protects babies from a form of the disease called disseminated TB but is far less effective at preventing pulmonary TB, the major cause of illness and deaths, in teens or adults.
Now, researchers from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and their colleagues have shown that simply changing the dose and route of administration from intradermal (ID) to intravenous (IV) greatly increases the vaccine’s ability to protect rhesus macaques from infection following exposure to Mycobacterium tuberculosis (Mtb), the bacterium that causes TB. The findings provide a new understanding of the mechanisms of BCG-elicited protection against tuberculosis infection and disease. In addition, the findings support investigation of IV BCG administration in clinical trials to determine whether this route improves its effectiveness in teens and adults.
Study investigators at the NIAID Vaccine Research Center were led by Robert A. Seder, M.D., and Mario Roederer, Ph.D. Their collaborators included JoAnne L. Flynn, Ph.D., of University of Pittsburgh School of Medicine.
Three-dimensional PET-CT scans of lungs showing areas of TB infection and tissue inflammation (red and orange) in macaques challenged with Mtb after vaccination with either ID BCG (top row) or IV BCG (bottom). Photo credit: University of Pittsburgh School of Medicine