Mount Sinai researchers have published what they say is the first study to identify a new form of treatment for rapid eye movement (REM) sleep behavior disorder. This condition affects more than 3 million Americans, mostly adults over the age of 50, who often unknowingly physically act out their dreams with vocal sounds or sudden, violent arm and leg movements during slumber, leading to significant injury to themselves or bed partners.
The new study, published in the Journal of Neuroscience on May 25, outlines a novel model to better characterize how REM sleep behavior disorder develops due to neurodegeneration—when brain cells lose function over time—which is associated with the accumulation of tau protein. This model provides an early-life biomarker of impending deterioration of the brain, which could guide future prevention and treatment.
The paper also demonstrates for the first time that sleep medications known as dual orexin receptor antagonists—commonly used to treat insomnia, or difficulty falling and remaining asleep—can significantly reduce REM sleep behavior disorder. Current therapeutic options for this disorder are primarily limited to melatonin and clonazepam, also known as Klonopin, so these findings suggest a promising new treatment with potentially fewer side effects.
"We were interested in understanding all of the ways in which sleep quality breaks down as neurodegeneration progresses and whether there were any ways to mitigate such changes," said corresponding author Andrew W. Varga, MD, PhD, Associate Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai. "We identify a novel model in which REM sleep behavior disorder can develop, due to neurodegeneration associated with accumulation of tau protein, and a novel therapy that could minimize REM sleep behavior disorder."
Mount Sinai researchers used a mouse model to study neurodegenerative disorders by examining the brain following abnormal deposits of tau, a protein that normally helps stabilize the internal skeleton of nerve cells in the brain. They analyzed behavioral states including wakefulness, phases of REM (sleep with dreams), phases of non-REM (sleep without dreams), length of sleep, transitions from waking to sleep, and how some factors are related to age. Nearly a third of the older subjects exhibited dream enactment behaviors reminiscent of REM sleep behavior disorder, including chewing and limb extension. After administering a dual orexin receptor antagonist twice during a 24-hour period, to evaluate sleep in light and dark phases, the researchers observed that the medication not only reduced the time it took to fall asleep and increased both the quality and duration of sleep but also reduced levels of dream enactment.
Researchers hope their findings will encourage future trials of dual orexin receptor antagonists to treat REM sleep behavior disorder in humans, given that the medication is already FDA approved and available to treat people with insomnia.
"We anticipated finding breakdown of sleep quality with progressive neurodegeneration related to tau accumulation, but the observation of dream enactment was a surprise," said lead author Korey Kam, PhD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at Icahn Mount Sinai. "It was even more surprising and exciting to observe that a dual orexin receptor antagonist could significantly minimize the dream enactment behaviors."
The research was supported by funding from the Alzheimer's Association and Merck Investigator Studies Program.
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population.
Ranked No. 14 nationwide in National Institutes of Health funding and in the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 34 academic departments and 44 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, and gastrointestinal and liver diseases.
Icahn Mount Sinai offers highly competitive MD, PhD, and master's degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. In addition, more than 535 postdoctoral research fellows are in training within the Health System.
A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai's technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into health care products and services that benefit the public.
Icahn Mount Sinai's commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School's programs. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others.
The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai's location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Beth Israel; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
