Wednesday, January 10, 2018
An experimental treatment developed from cattle plasma for Middle East respiratory syndrome (MERS) coronavirus infection shows broad potential, according to a small clinical trial led by National Institutes of Health scientists and their colleagues. The treatment, SAB-301, was safe and well tolerated by healthy volunteers, with only minor reactions documented.
The first confirmed case of MERS was reported in Saudi Arabia in 2012. Since then, the MERS coronavirus has spread to 27 countries and sickened more than 2,000 people, of whom about 35 percent have died, according to the World Health Organization. There are no licensed treatments for MERS.
SAB-301 was developed by SAB Biotherapeutics of Sioux Falls, South Dakota, and has been successfully tested in mice. The treatment comes from so-called “transchromosomic cattle.” These cattle have genes that have been slightly altered to enable them to produce fully human antibodies instead of cow antibodies against killed microbes with which they have been vaccinated — in this case the MERS virus. The clinical trial, conducted by NIH’s National Institute of Allergy and Infectious Diseases, took place at the NIH Clinical Center.
The round, spiked objects at center are MERS coronavirus particles.
Tuesday, January 2, 2018
Stem cell-derived retinal cells need primary cilia to support survival of light-sensing photoreceptors.
Scientists at the National Eye Institute (NEI), part of the National Institutes of Health, report that tiny tube-like protrusions called primary cilia on cells of the retinal pigment epithelium (RPE) — a layer of cells in the back of the eye — are essential for the survival of the retina’s light-sensing photoreceptors. The discovery has advanced efforts to make stem cell-derived RPE for transplantation into patients with geographic atrophy, otherwise known as dry age-related macular degeneration (AMD), a leading cause of blindness in the U.S. The study appears in the January 2 Cell Reports.
“We now have a better idea about how to generate and replace RPE cells, which appear to be among the first type of cells to stop working properly in AMD,” said the study’s lead investigator, Kapil Bharti, Ph.D., Stadtman Investigator at the NEI. Bharti is leading the development of patient stem cell-derived RPE for an AMD clinical trial set to launch in 2018.
In a healthy eye, RPE cells nourish and support photoreceptors, the cells that convert light into electrical signals that travel to the brain via the optic nerve. RPE cells form a layer just behind the photoreceptors. In geographic atrophy, RPE cells die, which causes photoreceptors to degenerate, leading to vision loss.
Mature iPSC-derived RPE cells under super resolution
Friday, December 22, 2017
Since 2016, when Zika was declared by WHO as a public health emergency of international concern, the virus has become established in more than 80 countries, infected millions of people, and left many babies with birth defects (collectively called congenital Zika syndrome). Although scientists have made progress in their understanding of the virus and its mosquito carrier, and are working toward treatments and a preventive vaccine, it would be premature to think that the Zika pandemic is now under control and will not reemerge, perhaps more aggressively, say leaders from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The Journal of Infectious Diseases published online December 16 a special supplement of articles examining current scientific knowledge about the Zika virus and the key research questions that remain. The supplement was sponsored and edited by NIAID and features several articles written by NIAID scientists.
Zika virus particles (red) shown in African green monkey kidney cells
Thursday, December 21, 2017
Plant molecule could be used to block postoperative incisional pain.
A promising approach to post-operative incision-site pain control uses a naturally occurring plant molecule called resiniferatoxin (RTX). RTX is found in Euphorbia resinifera, a cactus-like plant native to Morocco, which is 500 times more potent than the chemical that produces heat in hot peppers, and may help limit the use of opioid medication while in the hospital and during home recovery.
In a paper published online in Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists, researchers found that RTX could be used to block postoperative incisional pain in an animal model. Many medical providers turn to opioids, such as morphine or fentanyl, for moderate to severe post-operative pain relief, but these often come with side effects that can interfere with recovery, including respiratory depression, inhibition of gut motility and constipation, nausea and vomiting. Prolonged use of opioids can produce tolerance and introduces the risk of misuse. RTX is not an opioid and does not act in the brain but rather on the nerve endings in the skin. Scientists found that it can be used to block pain from the surgical incision selectively for approximately 10 days.
Wednesday, December 20, 2017
Using fruit flies, NIH researchers provide molecular basis for theory of aging.
A shorter life may be the price an organism pays for coping with the natural assaults of daily living, according to researchers at the National Institutes of Health and their colleagues in Japan. The scientists used fruit flies to examine the relationship between lifespan and signaling proteins that defend the body against environmental stressors, such as bacterial infections and cold temperatures. Since flies and mammals share some of the same molecular pathways, the work may demonstrate how the environment affects longevity in humans.
Appearing in the Proceedings of the National Academy of Sciences, the research identified Methuselah-like receptor-10 (Mthl10), a protein that moderates how flies respond to inflammation. The finding provides evidence for one theory of aging, which suggests longevity depends on a delicate balance between proinflammatory proteins, thought to promote aging, and anti-inflammatory proteins, believed to prolong life. These inflammatory factors are influenced by what an organism experiences in its every day environment.
Corresponding author Stephen Shears, Ph.D., of the National Institute of Environmental Health Sciences (NIEHS) at NIH, explained that Mthl10 appears on the surface of insect cells and acts as the binding partner to a signaling molecule known as growth-blocking peptide (GBP). Once Mthl10 and GBP connect, they initiate the production of proinflammatory proteins, which, in turn, shortens the fly’s life. However, removing the Mthl10 gene makes the flies unable to produce Mthl10 protein and prevents the binding of GBP to cells. As a result, the flies experienced low levels of inflammation and longer lifespans.
"Fruit flies without Mthl10 live up to 25 percent longer," Shears said. "But, they exhibit higher death rates when exposed to environmental stressors."
The binding of GBP to Mthl10 promotes inflammation, which decreases the lifespan of a fruit fly. In contrast, the removal of GBP’s binding partner Mthl10, produces less inflammation and increases the lifespan of the fly.
Tuesday, December 19, 2017
Researchers find target to protect hearing during chemotherapy treatment.
Scientists have found a new way to explain the hearing loss caused by cisplatin, a powerful drug used to treat many forms of cancer. Using a highly sensitive technique to measure and map cisplatin in mouse and human inner ear tissues, researchers found that forms of cisplatin build up in the inner ear. They also found a region in the inner ear that could be targeted for efforts to prevent hearing loss from cisplatin. The study is published in Nature Communications, and was supported by the National Institute on Deafness and other Communications Disorders (NIDCD), part of the National Institutes of Health.
Cisplatin and similar platinum-based drugs are prescribed for an estimated 10 to 20 percent of all cancer patients. The NIH’s National Cancer Institute supported research that led to the 1965 discovery of cisplatin and continued development leading to its success as an essential weapon in the battle against cancer. The drugs cause permanent hearing loss in 40 to 80 percent of adult patients and at least half of children who receive the drug. The new findings help explain why cisplatin is so toxic to the inner ear, and why hearing loss gets worse after each treatment, can occur long after treatment, and is more severe in children than adults.
Cisplatin (appearing in green) in the stria vascularis of a mouse inner ear.
Thursday, December 14, 2017
Scientists have identified differences in a group of genes they say might help explain why some people need a lot more sleep — and others less — than most. The study, conducted using fruit fly populations bred to model natural variations in human sleep patterns, provides new clues to how genes for sleep duration are linked to a wide variety of biological processes.
Researchers say a better understanding of these processes could lead to new ways to treat sleep disorders such as insomnia and narcolepsy. Led by scientists with the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, the study will be published on Dec. 14 in PLOS Genetics.
“This study is an important step toward solving one of the biggest mysteries in biology: the need to sleep,” says study leader Susan Harbison, Ph.D., an investigator in the Laboratory of Systems Genetics at NHLBI. “The involvement of highly diverse biological processes in sleep duration may help explain why the purpose of sleep has been so elusive.”
Graph showing sleep duration (in minutes) of wild fruit flies—long sleepers, normal sleepers, and short sleepers—artificially bred across 13 generations.
Monday, December 4, 2017
Vaccine developed by NIH scientists shows promise in Phase 1 testing.
Results from two Phase 1 clinical trials show an experimental Zika vaccine developed by government scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is safe and induces an immune response in healthy adults. The findings will be published on Dec. 4 in The Lancet. NIAID is currently leading an international effort to evaluate the investigational vaccine in a Phase 2/2b safety and efficacy trial.
“Following early reports that Zika infection during pregnancy can lead to birth defects, NIAID scientists rapidly created one of the first investigational Zika vaccines using a DNA-based platform and began initial studies in healthy adults less than one year later,” said NIAID Director Anthony S. Fauci, M.D. “NIAID has begun Phase 2 testing of this candidate to determine if it can prevent Zika virus infection, and the promising Phase 1 data published today support its continued development.”
Investigators from NIAID’s Vaccine Research Center (VRC) and Laboratory of Viral Diseases, part of the Division of Intramural Research, developed the investigational vaccine, which includes a small, circular piece of DNA called a plasmid. Scientists inserted genes into the plasmid that encode two proteins found on the surface of the Zika virus. After the vaccine is injected into muscle, the body produces proteins that assemble into particles that mimic the Zika virus and trigger the body to mount an immune response.
Thursday, November 30, 2017
Allergens are widespread, but highly variable in U.S. homes, according to the nation’s largest indoor allergen study to date. Researchers from the National Institutes of Health report that over 90 percent of homes had three or more detectable allergens, and 73 percent of homes had at least one allergen at elevated levels. The findings were published November 30 in the Journal of Allergy and Clinical Immunology.
“Elevated allergen levels can exacerbate symptoms in people who suffer from asthma and allergies, so it is crucial to understand the factors that contribute,” said Darryl Zeldin, M.D., senior author and scientific director at the National Institute of Environmental Health Sciences (NIEHS), which is part of NIH.
Using data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), the researchers studied levels of eight common allergens – cat, dog, cockroach, mouse, rat, mold, and two types of dust mite allergens – in the bedrooms of nearly 7,000 U.S. homes.
Factors contributing to elevated bedroom allergen levels include presence of pets and pests, type of housing, and living in rural areas. Individual allergens vary by geographic area.
Wednesday, November 29, 2017
NIH-supported study provides evidence for implementing approach broadly.
A study published today in the New England Journal of Medicine provides real-world evidence that implementing a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections in a population.
Investigators found that HIV incidence dropped by 42 percent among nearly 18,000 people in Rakai District, Uganda, during a seven-year period in which the rates of HIV treatment and voluntary medical male circumcision increased significantly.
The HIV prevention strategy whose impact was observed in the study is based on earlier findings by the National Institutes of Health and others demonstrating the protective effect of voluntary medical male circumcisionfor HIV-uninfected men and of HIV-suppressing antiretroviral therapy (ART) for halting sexual transmission of the virus to uninfected partners. The strategy is also based on studies showing that changes in sexual behavior, such as having only one sexual partner, can help prevent HIV infection.
A research assistant draws blood for HIV testing from a participant in the Rakai Community Cohort Study. Credit: Rakai Health Sciences Program