Dual orexin receptor antagonists (DORAs), a class of drugs approved to treat insomnia, may also be effective for rapid eye movement sleep behavior disorder (RBD), a new study suggests.
About 3 million people in the United States have RBD, which is often a precursor to Parkinson’s disease. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking and exhibiting other behaviors while asleep.
Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD.
Dr Andrew Varga
“REM behavior disorder is difficult to treat, and the treatments are mostly limited to clonazepam and melatonin,” which may have side effects, senior investigator Andrew Varga, MD, PhD, associate professor of pulmonary, critical care and sleep medicine at the Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News. “We’re using something completely different, which raises the possibility this might be something useful for REM behavior disorders.”
The findings, with Mount Sinai assistant professor Korey Kam, PhD, as lead author, were published online May 25 in the Journal of Neuroscience.
A New Model for RBD?
RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson’s disease that involve the formation of clumps of alpha-synuclein protein in the brain.
Prior research on RBD was done in synucleinopathy mouse models. For this study, however, researchers used a tauopathy mouse model to investigate how the abnormal accumulation of tau protein might affect RBD.
Researchers collected data on biophysical properties when the mice were awake and in REM and non-REM sleep. They examined length of sleep, transitions from waking to sleep, and how some factors are related to age.
Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension.
But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD.
The “Bigger Highlight”
Finding RBD behaviors in a tauopathy animal model was surprising, Varga said, because RBD has been previously linked to synucleinopathies. There was no known correlation between RBD and abnormal accumulation of tau.
Another unexpected finding was the detection of RBD in some of the younger animals, who had not yet shown evidence of tau accumulation.
“It appears to be a biomarker or a signature of something that’s going on that predicts the impending tauopathy at a time where there is very little, or no, tau pathology going on in the brain,” Varga said.
If RBD is an early predictor of future tau accumulation, the model could guide future prevention and treatment. However, the more important finding is the potential new treatment for the condition.
“The bigger highlight here is less about what’s causing the RBD as to what you can do to make it better,” he said.
The next step in the work is to study whether the effect of DORAs on RBD seen in this tauopathy mouse model is evidenced in other animals and whether it is effective in humans with RBD, Varga said.
The study was funded by the Alzheimer’s Association and Merck Investigator Studies Program. Kam, Varga, and co-authors report no relevant financial relationships.
J Neurosci. Published online May 25, 2203. Abstract
Kelli Whitlock Burton is a reporter for Medscape Medical News covering neurology and psychiatry.
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