February 9, 2022
The National Institutes of Health (NIH) is our nation’s medical research agency. Its mission focuses on scientific discoveries that improve health and save lives. Founded in 1870, the NIH conducts its own scientific research through its Intramural Research Program (IRP), which supports approximately 1,200 principal investigators and more than 4,000 postdoctoral fellows conducting basic, translational and clinical research. In this blog, we will highlight recent innovative NIH research.
Recent NIH Research
NIH researchers develop first stem cell model of albinism to study related eye conditions
Oculocutaneous albinism (OCA) is a group of inherited disorders characterized by the reduction of pigmentation in the eye, skin, and hair resulting from mutations in the genes that are responsible for melanin pigment production. Abnormalities caused by a lack of sufficient melanin pigment production include vision problems and susceptibility to sun damage to the skin.
Researchers at the National Eye Institute (NEI) have developed the first patient-derived stem cell model for studying eye conditions related to OCA. “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 Dr. Aman George, staff scientist in the NEI Ophthalmic Genetics and Visual Function Branch, and the lead author of the report.
Pigment is present in the retinal pigment epithelium (RPE) of the eye which aids vision by preventing the scattering of light. Scientists think that RPE plays a key role in forming these structures and want to better understand how lack of pigment affects their development. People with OCA have misrouted optic nerve fibers, lack pigmented RPE, and have an underdeveloped fovea, an area within the retina that is necessary for central vision. Scientists think that RPE plays a role in forming these structures and want to understand how lack of pigment affects their development.
“Treating albinism at a very young age, perhaps even prenatally, when the eye’s structures are forming, would have the greatest chance of rescuing vision,” said Dr. Brian Brooks, NEI clinical director and chief of the Ophthalmic Genetics and Visual Function Branch “In adults, benefits might be limited to improvements in photosensitivity, for example, but children may see more dramatic effects.” The team is now exploring how to use their model for high-throughput screening of potential therapies for the treatment of OCA.
Oral immunotherapy induces remission of peanut allergy in some young children
Peanut allergy, one of the most common food allergies, affects about 2% of children in the United States, or nearly 1.5 million individuals under the age of 18. Exposure to even a small amount of peanut protein can lead to a life-threatening allergic reaction know as anaphylaxis.
In a recent clinical trial funded by the National Institutes of Health (NIH), a team of researchers concluded that providing peanut oral immunotherapy to highly peanut-allergic children safely desensitized the majority of them to peanut protein and induced remission of peanut allergy in one-fifth of the study participants. Nearly 150 children ages 1 to 3 years took part in the IMPACT trial at five academic medical centers in the United States. Only children who had an allergic reaction after eating half a gram of peanut protein or less were eligible to join the study.
The immunotherapy consisted of a daily oral dose of peanut flour for 2.5 years. Remission was defined as being able to eat 5 grams of peanut protein, equivalent to 1.5 tablespoons of peanut butter, without having an allergic reaction six months after completing immunotherapy. The youngest children and those who started the trial with lower levels of peanut-specific antibodies were most likely to achieve remission.
The research team found two key predictive factors that a child would achieve remission following the therapy: lower levels of peanut-specific immunoglobulin E antibodies at the start of the trial and being younger in age. The study data indicated an inverse relationship between age at the start of the trial and remission, with 71% of the 1-year-olds, 35% of the 2-year-olds and 19% of the 3-year-olds experiencing remission.
“The landmark results of the IMPACT trial suggest a window of opportunity in early childhood to induce remission of peanut allergy through oral immunotherapy,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID). “It is our hope that these study findings will inform the development of treatment modalities that reduce the burden of peanut allergy in children.” NIAID sponsored the trial and funded it through its Immune Tolerance Network.
NIH study classifies vision loss and retinal changes in Stargardt disease
In a recent study conducted by the National Eye Institute (NEI), a team of researchers developed an artificial-intelligence-based method to evaluate patients with Stargardt, an inherited an eye disease that begins in childhood and leads to the progressive loss of vision. An estimated 1 in 10,000 people have Stargardt disease. This novel method quantifies disease-related loss of light-sensing retina cells that will enable a better understanding of the genetic causes of the disease and insights into the development of therapies for the treatment of the disease.
The most common form of Stargardt is 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.
Among patients who all have ABCA4 gene variants, there can be a wide spectrum in terms of age of onset and disease progression.
“Different variants of the ABCA4 gene are likely driving the different disease characteristics, or phenotypes. However, conventional approaches to analyzing structural changes in the retina have not allowed us to correlate genetic variants with phenotype,” said the study’s co-leader, Dr. Brian Brooks, chief of the NEI Ophthalmic Genetics & Visual Function Branch. Dr. Brooks co-led the study with Dr. Brett Jeffrey, head of the Human Visual Function Core of the NEI’s Ophthalmic Genetics and Visual Function Branch.
The study followed 66 Stargardt patients for a period of five years using a retinal imaging technology called spectral-domain optical coherence tomography (SD-OCT). The 3D cross-sectional retinal images were and analyzed using deep learning, a type of artificial intelligence (AI) in which vast amounts of imaging data can be fed into an algorithm, which then learns to detect patterns that allow the images to be classified. This methodology allowed the researchers to quantify and compare the loss of photoreceptors and various layers of the retina according to the patient’s phenotype and ABCA4 variant and provided a way of classifying the severity of 31 different ABCA4 variants.
“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 Dr. Michael Chiang, director of the NEI.
Researchers highlight COVID-19 neurological symptoms and need for rigorous studies
Acute COVID-19 infection, caused by the SARS-CoV-2 virus, can sometimes lead to long-lasting effects, collectively termed as “Long Covid”. This can include a wide variety of symptoms in the brain and nervous system that range from a loss of taste and smell, impaired concentration, fatigue, pain, headache, sleep disorders, and autonomic disorders to psychological effects such as depression or psychosis.
Although SARS-CoV-2 was initially identified as a respiratory virus, it can affect the entire body. Neurological symptoms that have been reported with acute COVID-19 include loss of taste and smell, headaches, stroke, delirium, and brain inflammation. There does not seem to be extensive infection of brain cells by the virus, but the neurological effects may be caused by immune activation, neuroinflammation, and damage to brain blood vessels.
In a recent Viewpoint published in Science by Dr. Avindra Nath, clinical director of the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS), and Dr. Serena Spudich, Yale School of Medicine, highlight current scientific insights surrounding the effects of SARS-CoV-2 on the brain, and how physiological responses to acute COVID-19 infection could lead to Long Covid symptoms. Dr. Nath and Dr. Spudich also outline common risk factors between individuals with Long Covid and those living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or post-Lyme disease.
The authors emphasize the need for the further study of individuals with Long Covid, categorized by their specific symptoms, as being crucial to the development of diagnostic and therapeutic tools to identify and treat what is becoming a significant public health concern.
NIH launches first phase of $9.8 million competition to accelerate development of neuromodulation therapies
The National Institutes of Health (NIH) has launched the first phase of the Neuromod Prize, a $9.8 million competition dedicated to accelerating the development of targeted neuromodulation therapies. The Neuromod Prize is part of the SPARC (Stimulating Peripheral Activity to Relieve Conditions) initiative from the NIH Common Fund and focuses on novel uses of peripheral nerve stimulation treatments that selectively target multiple organs and functions. The competition seeks scientists, engineers, and clinicians to submit innovative concepts and clinical development plans to demonstrate solutions for precisely stimulating the peripheral nervous system to treat disease and improve human health.
The first phase of the competition (Concepts and plans for development) will select up to eight winners who will receive a share of the up to $800,000 prize pool and will exclusively be invited to participate in phase two of the competition. The second phase (Proof-of-concept studies) will award a planned prize pool of $4 million. Up to four winners from the second phase may be selected to continue on to phase three (IDE-enabling studies), awarding up to $5 million. The competition is subject to change along with the availability of funds. Details surrounding phases two and three are expected to be announced at a future date.
“Through the Neuromod Prize, we’re asking potential solvers to use the foundational knowledge and technologies that have come out of our SPARC program and take it to the next level with their innovative concepts and ideas,” said Dr. James Anderson, director of the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), which oversees the NIH Common Fund. “This competition is an exciting opportunity to come up with tangible plans for harnessing the power of the body’s electrical system to help transform treatments for millions of people living with chronic or acute illnesses.”
For more information about the Neuromod Prize, visit neuromodprize.com.
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