Friday, May 15, 2020
A single dose of ChAdOx1 nCoV-19, an investigational vaccine against SARS-CoV-2, has protected six rhesus macaques from pneumonia caused by the virus, according to National Institutes of Health scientists and University of Oxford collaborators. SARS-CoV-2 is the virus that causes COVID-19. The researchers posted their data to the preprint server bioRxiv. The findings are not yet peer-reviewed but are being shared to assist the public health response to COVID-19. Based on these data, a Phase 1 trial of the candidate vaccine began on April 23 in healthy volunteers in the United Kingdom.
The vaccine was developed at the University of Oxford Jenner Institute. It uses a replication-deficient chimpanzee adenovirus to deliver a SARS-CoV-2 protein to induce a protective immune response. ChAdOx1 has been used to develop investigational vaccines against several pathogens, including a closely related coronavirus that causes Middle East respiratory syndrome (MERS). The scientists quickly adapted the platform to SARS-CoV-2 when the first cases of COVID-19 emerged. They showed that the vaccine rapidly induced immune responses against SARS-CoV-2 in mice and rhesus macaques. They then conducted vaccine efficacy testing on the macaques at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana. Six animals that received the investigational vaccine 28 days before being infected with SARS-CoV-2 were compared with three control animals that did not receive the vaccine. The vaccinated animals showed no signs of virus replication in the lungs, significantly lower levels of respiratory disease and no lung damage compared to control animals.
This scanning electron microscope image shows SARS-CoV-2 (orange) — also known as 2019-nCoV, the virus that causes COVID-19 — isolated from a patient in the U.S., emerging from the surface of cells (green) cultured in the lab.
Thursday, May 14, 2020
Treatment with disulfiram, normally prescribed to treat alcohol use disorder, shows health benefits in animal study
An off-label experiment in mice using disulfiram, which has been used to treat alcohol use disorder for more than 50 years, consistently normalized body weight and reversed metabolic damage in obese middle-aged mice of both sexes. The international study was led by researchers at the National Institute on Aging (NIA), part of the National Institutes of Health . The results were published online in the journal Cell Metabolism on May 14.
The scientific team studied groups of 9-month-old lab mice who had been fed a high-fat diet for 12 weeks. As expected, this diet made the mice overweight and they started to show signs of pre-diabetes-like metabolic problems, such as insulin resistance and elevated fasting blood sugar levels. Next, the scientists divided these mice into four groups to be fed four different diets for an additional 12 weeks: a standard diet alone, a high-fat diet alone, a high-fat diet with a low amount of disulfiram, or a high-fat diet with a higher amount of disulfiram. As expected, the mice who stayed on the high-fat diet alone continued to gain weight and show metabolic problems. Mice who switched to standard diet alone gradually saw their body weight, fat composition and blood sugar levels return to normal.
The mice in the remaining two groups, with either a low or high dose of disulfiram added to their still-fatty food, showed a dramatic decrease in their weight and related metabolic damage. Mice on the high disulfiram dose lost as much as 40% of their body weight in just four weeks, effectively normalizing their weight to that of obese mice who were switched back to standard diet. Mice in either disulfiram dose diet group became leaner and showed significant improvement in blood glucose levels on par with the mice who were returned to standard diet. Disulfiram treatment, which has few harmful side effects in humans, also appeared to protect the pancreas and liver from damage caused by pre-diabetic type metabolic changes and fat build up usually caused by eating a high-fat diet.
Tuesday, April 21, 2020
Findings point to targeting epigenome as a potential therapeutic strategy
National Eye Institute (NEI) researchers profiling epigenomic changes in light-sensing mouse photoreceptors have a clearer picture of how age-related eye diseases may be linked to age-related changes in the regulation of gene expression. The findings, published online April 21 in Cell Reports, suggest that the epigenome could be targeted as a therapeutic strategy to prevent leading causes of vision loss, such as age-related macular degeneration (AMD). NEI is part of the National Institutes of Health.
“Our study elucidates the molecular changes and biological pathways linked with aging of rod photoreceptors, light-sensing cells of the retina. Future investigations can now move forward to study how we can prevent or delay vision loss in aging and hopefully reduce the risk of associated neurodegeneration” said the study’s lead investigator, Anand Swaroop, Ph.D., senior investigator and chief of the NEI Neurobiology, Neurodegeneration, and Repair Laboratory.
Each organism is born with a genome, a library of genes that control all the body’s cellular and tissue functions. Expression of those genes — when information stored in DNA is converted into instructions for making proteins or other molecules — is modulated and maintained by the organism’s epigenome. The epigenome tags the DNA code to modify gene expression in ways that can be favorable and unfavorable for survival.
A simulation shows what the grocery store aisle looks like to someone with age-related macular degeneration. AMD damages the macula, a small spot near the center of the eye’s light-sensing retina. The macula lets us see objects that are straight ahead — it’s the part of the eye used for sharp, central vision.
Monday, April 20, 2020
Behavioral inhibition in infancy associated with introversion and internalizing psychopathology in adulthood
Researchers investigating how temperament shapes adult life-course outcomes have found that behavioral inhibition in infancy predicts a reserved, introverted personality at age 26. For those individuals who show sensitivity to making errors in adolescence, the findings indicated a higher risk for internalizing disorders (such as anxiety and depression) in adulthood. The study, funded by the National Institutes of Health and published in Proceedings of the National Academy of Sciences, provides robust evidence of the impact of infant temperament on adult outcomes.
“While many studies link early childhood behavior to risk for psychopathology, the findings in our study are unique,” said Daniel Pine, M.D., a study author and chief of the NIMH Section on Development and Affective Neuroscience. “This is because our study assessed temperament very early in life, linking it with outcomes occurring more than 20 years later through individual differences in neural processes.”
Temperament refers to biologically based individual differences in the way people emotionally and behaviorally respond to the world. During infancy, temperament serves as the foundation of later personality. One specific type of temperament, called behavioral inhibition (BI), is characterized by cautious, fearful, and avoidant behavior toward unfamiliar people, objects, and situations. BI has been found to be relatively stable across toddlerhood and childhood, and children with BI have been found to be at greater risk for developing social withdrawal and anxiety disorders than children without BI.
Friday, April 17, 2020
Study supports clinical testing under way across U.S.
Early treatment with the experimental antiviral drug remdesivir significantly reduced clinical disease and damage to the lungs of rhesus macaques infected with SARS-CoV-2, the coronavirus that causes COVID-19, according to National Institutes of Health scientists.
The study was designed to follow dosing and treatment procedures used for hospitalized COVID-19 patients being administered remdesivir in a large, multi-center, clinical trial led by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The scientists posted the work on the preprint server bioRxiv. The findings are not yet peer-reviewed and should not be considered clinical advice, but are being shared to assist the public health response to COVID-19. A study detailing the development of the rhesus macaque model of mild- to-moderate human disease, conducted by the same team of NIAID scientists, was posted to bioRxiv on March 21.
The current study of remdesivir, a drug developed by Gilead Sciences Inc. and NIAID-supported investigators, involved two groups of six rhesus macaques. One group of monkeys received remdesivir and the other animals served as an untreated comparison group. Scientists infected both groups with SARS-CoV-2. Twelve hours later the treatment group received a dose of remdesivir intravenously, and then received a daily intravenous booster dose thereafter for the next six days. The scientists timed the initial treatment to occur shortly before the virus reached its highest level in the animals’ lungs.
Friday, April 17, 2020
Vaccine neutralizes multiple MERS-CoV strains
An investigational vaccine called ChAdOx1 MERS protected two groups of rhesus macaques from disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV is a relative of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). National Institutes of Health scientists and colleagues are pursuing similar studies with ChAdOx1 SARS2, a vaccine candidate against SARS-CoV-2. They posted their results with ChAdOx1 MERS on a preprint server. The findings are not yet peer-reviewed but are being shared to assist the public health response to COVID-19.
ChAdOx1 MERS, which uses a replication-deficient chimpanzee adenovirus to deliver a MERS-CoV protein in recipients, also worked against six different strains of MERS-CoV when tested in mice as a single vaccination. Scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) at Rocky Mountain Laboratories in Hamilton, Mont., led the project. Collaborators work at the University of Oxford in the United Kingdom; researchers at the University of Oxford Jenner Institute developed the ChAdOx1 vaccine technology.
Colorized transmission electron micrograph showing particles of the Middle East Respiratory Syndrome Coronavirus that emerged in 2012.
Wednesday, April 15, 2020
Three methods effectively sanitized masks for limited re-use
N95 respirators can be decontaminated effectively and maintain functional integrity for up to three uses, according to National Institutes of Health scientists. N95 respirators are designed for single-use and are worn by healthcare providers to reduce exposure to airborne infectious agents, including the virus that causes COVID-19. The study was conducted in a controlled laboratory setting, and the results were posted on a preprint server today. The findings are not yet peer-reviewed but are being shared to assist the public health response to COVID-19.
The study investigators are with NIH’s Rocky Mountain Laboratories (RML) in Hamilton, Montana, part of the National Institute of Allergy and Infectious Diseases (NIAID). With collaborators from the University of California, Los Angeles, they tested the decontamination of small sections of N95 filter fabric that had been exposed to SARS-CoV-2, the virus that causes COVID-19. Decontamination methods tested included vaporized hydrogen peroxide (VHP), 70-degree Celsius dry heat, ultraviolet light, and 70% ethanol spray.
All four methods eliminated detectable viable virus from the N95 fabric test samples. The investigators then treated fully intact, clean respirators with the same decontamination methods to test their reuse durability. Volunteer RML employees wore the masks for two hours to determine if they maintained a proper fit and seal over the face; decontamination was repeated three times with each mask using the same procedure.
Colorized scanning electron micrograph of an apoptotic cell (red) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.
Wednesday, April 15, 2020
NIH-funded study offers new path to modeling eye disease, advancing therapies
Researchers have discovered a technique for directly reprogramming skin cells into light-sensing rod photoreceptors used for vision. The lab-made rods enabled blind mice to detect light after the cells were transplanted into the animals’ eyes. The work, funded by the National Eye Institute (NEI), published April 15 in Nature. The NEI is part of the National Institutes of Health.
Up until now, researchers have replaced dying photoreceptors in animal models by creating stem cells from skin or blood cells, programming those stem cells to become photoreceptors, which are then transplanted into the back of the eye. In the new study, scientists show that it is possible to skip the stem-cell intermediary step and directly reprogram skins cells into photoreceptors for transplantation into the retina.
“This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors,” said Anand Swaroop, Ph.D., senior investigator in the NEI Neurobiology, Neurodegeneration, and Repair Laboratory, which characterized the reprogrammed rod photoreceptor cells by gene expression analysis.
Three months after transplantation, immunofluorescence studies confirmed the survival of the chemically induced photoreceptor-like cells (green). They also show integration of the cells into the layers of the mouse retina.
Tuesday, April 14, 2020
According to a recent analysis of data from two major eye disease studies, adherence to the Mediterranean diet — high in vegetables, whole grains, fish, and olive oil — correlates with higher cognitive function. Dietary factors also seem to play a role in slowing cognitive decline. Researchers at the National Eye Institute (NEI), part of the National Institutes of Health, led the analysis of data from the Age-Related Eye Disease Study (AREDS) and AREDS2. They published their results today in the journal Alzheimer’s and Dementia.
“We do not always pay attention to our diets. We need to explore how nutrition affects the brain and the eye,” said Emily Chew, M.D., director of the NEI Division of Epidemiology and Clinical Applications and lead author of the studies.
The researchers examined the effects of nine components of the Mediterranean diet on cognition. The diet emphasizes consumption of whole fruits, vegetables, whole grains, nuts, legumes, fish, and olive oil, as well as reduced consumption of red meat and alcohol.
Friday, April 10, 2020
A new study has begun recruiting at the National Institutes of Health in Bethesda, Maryland, to determine how many adults in the United States without a confirmed history of infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), have antibodies to the virus. The presence of antibodies in the blood indicates a prior infection. In this “serosurvey,” researchers will collect and analyze blood samples from as many as 10,000 volunteers to provide critical data for epidemiological models. The results will help illuminate the extent to which the novel coronavirus has spread undetected in the United States and provide insights into which communities and populations are most affected.
The study will be conducted by researchers at the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), with additional support from the National Center for Advancing Translational Sciences (NCATS) and the National Cancer Institute (NCI), all parts of NIH.
“This study will give us a clearer picture of the true magnitude of the COVID-19 pandemic in the United States by telling us how many people in different communities have been infected without knowing it, because they had a very mild, undocumented illness or did not access testing while they were sick,” said Anthony S. Fauci, M.D., NIAID director. “These crucial data will help us measure the impact of our public health efforts now and guide our COVID-19 response moving forward.”
Colorized scanning electron micrograph of an apoptotic cell (blue) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.