Thursday, March 8, 2018
Monoclonal antibodies (mAbs) — preparations of a specific type of antibody designed to bind to a single target — have shown promise in the fight against cancer and autoimmune diseases. They also may play a critical role in future battles against emerging infectious disease outbreaks, according to a new article by scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The article is published online this week by the New England Journal of Medicine and outlines the potential uses for mAbs as treatments for infectious diseases and as a prevention tool for protecting individuals at risk of infection and slowing disease outbreaks.
The article, written by NIAID Director Anthony S. Fauci, M.D., and colleagues Hilary D. Marston, M.D., M.P.H., and Catharine I. Paules, M.D., highlights the research advances that could allow for rapid, strategic deployment of mAbs to prevent and treat emerging infectious diseases and, potentially, alter the course of epidemics.
Ebola virus particles (red) on a larger cell. ZMAPP, a potential treatment for Ebola, includes a cocktail of monoclonal antibodies.
Thursday, March 8, 2018
Familial human prion diseases are passed within families and are associated with 34 known prion protein mutations. To determine whether three of the unstudied mutations are transmissible, scientists from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, exposed research mice to brain samples from three people who died from a familial prion disease. After observing the mice for about two years, they found two of the mutations, Y226X and G131V, are transmissible.
Perhaps more interesting, the Y226X patient sample had previously been preserved in formaldehyde for three days, embedded in wax, and dried on glass specimen slides for several years before being rehydrated for the study. Yet, the sample infected four of eight mice.
The finding illustrates the hardiness of prion infectivity and the potential risks associated with prion transmission, potentially through surgery, blood transfusion or tissue donation. Samples for the other two mutations studied were taken from frozen brain tissue that was thawed.
Thursday, March 1, 2018
Researchers can predict variants’ impact, recall participants to test predictions
Databases such as the 1000 Genomes Project and the Exome Aggregation Consortium (ExAC) harbor large numbers of genotypes (an individual’s collection of genes). Until now, it has been difficult for researchers to re-contact individuals with genotypes of interest and investigate the health consequences of their genes and gene variants. To address this challenge, National Institutes of Health and Inova Health System researchers are launching The Genomic Ascertainment Cohort (TGAC), a two-year pilot project that will allow them to recall genotyped people and examine the genes and gene variants’ influence on their phenotypes, an individual’s observable traits, such as height, eye color or blood type.
The project reverses a long-standing research paradigm of examining a person’s traits or symptoms and then searching for genes or gene variants that cause or contribute to them. NIH will establish a new database of 10,000 human genomes and exomes, the 1-2 percent of the genome that contains protein-coding genes. Once the database is established, NIH and Inova researchers will predict conditions that specific genes or gene variants might produce and test those predictions by re-examining individuals who donated their DNA sequence information to the database. TGAC will be based in the Washington, D.C., area and only people who’ve expressly given consent to be re-contacted will participate in TGAC.
“We’re trying to advance science in a new, creative and slightly radical way,” said Leslie Biesecker, M.D., TGAC co-organizer and chief of the Medical Genomics and Metabolic Genetics Branch at NIH’s National Human Genome Research Institute (NHGRI). “Our goal is to determine what genes and gene variants do. We’re especially interested in using this as a platform to test our ability to predict phenotype from genotype – one of the key underpinnings of predictive genomic medicine.” NHGRI will host the database and administer the program.
Monday, February 26, 2018
Study in mice suggests that experimental drug may be effective against mountain sickness and other polycythemias
Researchers at the National Institutes of Health have cured mice with Chuvash polycythemia, a life-threatening disorder that involves the overproduction of red blood cells. They treated the mice using Tempol, an experimental drug being studied for treatment of diabetes, cancer and other diseases. The findings offer hope that Tempol or a similar drug may treat polycythemias that affect humans, such as mountain sickness—a serious blood complication experienced in low-oxygen, high-altitude settings. The study appears in The Journal of Clinical Investigation.
Chuvash polycythemia is a rare, inherited disorder that is endemic to the Chuvash Republic of Russia, though it does occur in other parts of the world. NIH studies rare diseases not only to help the people who have them, but also to gain insight into gene functions that may benefit people with more common conditions. Complications of Chuvash polycythemia include blood clots and cerebral hemorrhage. The condition results from a genetic mutation that makes people unable to break down hypoxia inducible factor 2α (HIF2α), a protein that helps stimulate red blood cell production. The inability to degrade HIF2α leads to higher red cell production, even under high-oxygen conditions.
Friday, February 23, 2018
Natural history investigation will deploy latest advances to identify biomarkers, targets for early therapy
A new clinical study led by the National Eye Institute (NEI), part of the National Institutes of Health, will follow 500 people over five years to learn more about the natural history of early age-related macular degeneration (AMD). By using the latest technologies to visualize structures within the eye and measure their function, researchers hope to identify biomarkers of disease progression, well before it advances to late-stage disease and causes vision loss. AMD is the leading cause of vision impairment and blindness among people age 50 and older in the United States.
“The findings will contribute to our understanding of the underlying biology driving the transition from early to late-stage disease so that therapies can be developed to halt its progression,” said the study’s lead investigator, Emily Y. Chew, M.D., deputy clinical director at NEI and director of the NEI Division of Epidemiology and Clinical Applications. “Treatments that halt the disease at its early stage would have an enormous public health impact.”
Fundus photo shows giraffe-like macular pattern in the retina of a person with reticular pseudodrusen.
Friday, February 9, 2018
National Institutes of Health scientists developing a rapid, practical test for the early diagnosis of prion diseases have modified the assay to offer the possibility of improving early diagnosis of Parkinson’s disease and dementia with Lewy bodies. The group, led by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), tested 60 cerebral spinal fluid samples, including 12 from people with Parkinson’s disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 of whom had Alzheimer’s disease. The test correctly excluded all the 31 controls and diagnosed both Parkinson’s disease and dementia with Lewy bodies with 93 percent accuracy.
Importantly, test results were available within two days, compared to related assays that require up to 13 days. The group conducted the tests using Real-Time Quaking-Induced Conversion (RT-QuIC), an assay developed and refined over the past decade at NIAID’s Rocky Mountain Laboratories. Scientists from the University of California San Diego, University of Verona in Italy, Indiana University School of Medicine, Indianapolis, and the Case Western Reserve University School of Medicine, Cleveland, collaborated on the project. The research findings were published in Acta Neuropathologica Communications.
NIAID’s Bradley Groveman, foreground, and Christina Orru using the RT-QuIC diagnostic assay, which they helped adapt to detect Parkinson’s disease and dementia with Lewy bodies.
Thursday, February 8, 2018
Ebola virus can infect the reproductive organs of male and female macaques, according to a study published in The American Journal of Pathology, suggesting that humans could be similarly infected. Prior studies of survivors of the 2014-2016 Ebola outbreak in West Africa have revealed sexual transmission of Ebola virus, and that viral RNA (Ebola virus genetic material) can persist in semen following recovery. While little is known about viral persistence in female reproductive tissues, pregnant women with Ebola virus disease have a maternal death rate of more than 80 percent and a fetal death rate of nearly 100 percent.
In this study, investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and from Thomas Jefferson University infected four female and eight male macaques with the Makona variant of Ebola virus, the variant responsible for the recent West Africa outbreak. All the macaques succumbed to Ebola virus disease and were euthanized six to nine days after infection. The scientists then took reproductive tissue samples from each macaque and analyzed the samples for signs of Ebola virus infection, organ and tissue damage, and immune responses. They found widespread Ebola virus infection of reproductive organs with minimal tissue immune response or signs of disease.
Colorized transmission electron micrograph of the ovary from a nonhuman primate infected with Ebola virus. Characteristic filamentous Ebola virus particles are present between cells (bright red). Intracytoplasmic Ebola virus inclusion bodies forming crystalline arrays can be seen within ovarian stromal cells (darker red).
Wednesday, February 7, 2018
Preliminary results suggest strokes also affect the eye
Research into curious bright spots in the eyes on stroke patients’ brain images could one day alter the way these individuals are assessed and treated. A team of scientists at the National Institutes of Health found that a chemical routinely given to stroke patients undergoing brain scans can leak into their eyes, highlighting those areas and potentially providing insight into their strokes. The study was published in Neurology.
“We were kind of astounded by this – it’s a very unrecognized phenomenon,” said Richard Leigh, M.D., an assistant clinical investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the paper’s senior author. “It raises the question of whether there is something we can observe in the eye that would help clinicians evaluate the severity of a stroke and guide us on how best to help patients.”
Eyes yield information about strokes: MRI scans revealed that a chemical called gadolinium, used to improve images, leaked into the eyes of stroke patients.
Wednesday, February 7, 2018
NIH study in rats suggests that support cells modulate brain circuit activity
Traditionally, scientists thought that star-shaped brain cells called astrocytes were steady, quiet supporters of their talkative, wire-like neighbors, called neurons. Now, an NIH study suggests that astrocytes may also have their say. It showed that silencing astrocytes in the brain’s breathing center caused rats to breathe at a lower rate and tire out on a treadmill earlier than normal. These were just two examples of changes in breathing caused by manipulating the way astrocytes communicate with neighboring cells.
“For decades we thought that breathing was exclusively controlled by neurons in the brain. Our results suggest that astrocytes actively help control the rhythm of breathing,” said Jeffrey C. Smith, Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study published in Nature Communications. “These results add to the growing body of evidence that is changing the way we think about astrocytes and how the brain works.”
A fresh look at the brain and breathing: NIH study in rats shows that star-shaped brain cells, called astrocytes (red), may play an active role in breathing.
Tuesday, February 6, 2018
Mouse nicotinamide riboside study shows potential for human research
The supplement nicotinamide riboside (NR) – a form of vitamin B3 – prevented neurological damage and improved cognitive and physical function in a new mouse model of Alzheimer’s disease. The results of the study, conducted by researchers at the National Institute on Aging (NIA) part of the National Institutes of Health, suggest a potential new target for treating Alzheimer’s disease. The findings appear in the Feb. 5, 2018, issue of Proceedings of the National Academy of Sciences.
NR acts on the brain by normalizing levels of nicotinamide adenine dinucleotide (NAD+), a metabolite vital to cellular energy, stem cell self-renewal, resistance to neuronal stress and DNA repair. In Alzheimer’s disease, the brain’s usual DNA repair activity is impaired, leading to mitochondrial dysfunction, lower neuron production, and increased neuronal dysfunction and inflammation.
The international team of scientists was led by Vilhelm A. Bohr, M.D., Ph.D., senior investigator and chief of the Laboratory of Molecular Gerontology of the NIA’s Intramural Research Program, with Dr. Yujun Hou, a postdoctoral investigator in the laboratory.
In a mouse model of Alzheimer’s disease, amyloid beta clusters (red) build up among neurons (green) in a memory-related area of the brain. With support from the National Center for Advancing Translational Sciences, scientists have found that a compound originally developed as a cancer therapy potentially could be used to treat Alzheimer’s disease.