Potential New Treatment for REM Sleep Behavior Disorder, Offering Hope to Millions

A team of researchers from Mount Sinai has conducted what they describe as the first study to identify a new treatment for rapid eye movement (REM) sleep behavior disorder. This condition affects a significant number of Americans, primarily adults over the age of 50, who unknowingly act out their dreams through vocal sounds or sudden, violent arm and leg movements during sleep, often resulting in injuries to themselves or their bed partners.

Published in the Journal of Neuroscience on May 25, the study presents a pioneering model that enhances our understanding of the development of REM sleep behavior disorder due to neurodegeneration. This process occurs when brain cells progressively lose function, often accompanied by the accumulation of tau protein. The model introduced in this study serves as an early-life biomarker, predicting impending deterioration of the brain, which could inform future prevention and treatment approaches.

Furthermore, the research demonstrates for the first time that dual orexin receptor antagonists, sleep medications commonly used to address insomnia, exhibit significant potential in reducing REM sleep behavior disorder. Currently, therapeutic options for this disorder are primarily limited to melatonin and clonazepam (also known as Klonopin). Hence, these findings offer a promising avenue for a new treatment that could potentially entail fewer side effects.

Lead 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, emphasized the study’s objective to comprehend the various ways in which sleep quality deteriorates during neurodegeneration and explore potential mitigation strategies. Dr. Varga explained, “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.”

To study neurodegenerative disorders, the Mount Sinai researchers utilized a mouse model, closely examining the brain after the abnormal deposition of tau protein—a substance that typically aids in stabilizing the internal structure of nerve cells in the brain. The team analyzed different behavioral states, including wakefulness, REM sleep (characterized by dreaming), non-REM sleep (dreamless sleep), sleep duration, transitions from wakefulness to sleep, and their association with age. They discovered that nearly one-third of the older subjects exhibited dream enactment behaviors similar to REM sleep behavior disorder, such as chewing and limb extension.

In a crucial breakthrough, the researchers administered a dual orexin receptor antagonist twice within a 24-hour period, assessing sleep patterns during both light and dark phases. The medication not only reduced the time taken to fall asleep and improved the quality and duration of sleep but also diminished levels of dream enactment.

The researchers are hopeful that their findings will encourage further clinical trials of dual orexin receptor antagonists for the treatment of REM sleep behavior disorder in humans, especially considering that the medication is already FDA-approved and available for individuals with insomnia.

Lead author Korey Kam, PhD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at Icahn Mount Sinai, expressed surprise at the observations made during the study. Kam stated, “We anticipated finding breakdown of sleep quality with progressive neurodegeneration related to tau accumulation, but the observation of dream enactment was a surprise. It was even more surprising and exciting to observe that a dual orexin receptor antagonist could significantly minimize the dream enactment behaviors.”

The research received support from the Alzheimer’s Association and the Merck Investigator Studies Program.

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