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Mount Sinai researchers claim to have discovered a novel therapy for rapid eye movement (REM) sleep behaviour disorder. This disorder affects approximately 3 million Americans, usually, seniors over the age of 50, who sometimes inadvertently physically play out their dreams during rest by making vocal noises or making abrupt, violent arm and leg movements, causing serious damage to themselves or their bedmates.
The new study, published in the Journal of Neuroscience, proposes a unique model to better characterise how REM sleep behaviour problem develops as a result of neurodegeneration, which is related to tau protein buildup. This model gives a biomarker of imminent brain damage in early life, which might guide future prevention and therapy. The study also shows for the first time that dual orexin receptor antagonists, which are routinely used to treat insomnia or difficulties falling and staying asleep, can considerably improve REM sleep behaviour disorder. Because the only current treatments for this illness are melatonin and clonazepam, popularly known as Klonopin, these findings suggest a viable new medication with perhaps fewer adverse 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." (ANI)
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