Resume: A new potential treatment has been identified for rapid eye movement (REM) sleep behavior disorder.
The study established a new model describing the progression of the condition as a result of neurodegeneration linked to accumulation of tau proteins. Researchers found dual orexin receptor antagonists, commonly used for insomnia, significantly reduced the symptoms of this condition.
The discovery introduces a new treatment option that may have fewer side effects.
- Mount Sinai researchers discovered a new potential treatment for REM sleep behavior disorder, which affects more than 3 million Americans and involves acting out dreams during sleep.
- The study presented a new model showing how the condition develops as a result of neurodegeneration related to an accumulation of tau protein.
- Sleep medications known as dual orexin receptor antagonists, usually used for insomnia, have been shown to significantly reduce the disorder, opening up a promising new treatment option.
Source: Mount Sinai Hospital
Mount Sinai researchers have published what they say is the first study identifying a new form of treatment for rapid eye movement (REM) sleep behavior disorder.
This condition affects more than 3 million Americans, mostly adults over age 50, who often unknowingly act out their dreams physically with vocal sounds or sudden, violent arm and leg movements during sleep, leading to significant harm to themselves or bed partners.
The new study, published in the Journal of Neuroscienceoutlines a new model to better characterize how REM sleep behavior disorder develops as a result of neurodegeneration – when brain cells lose function over time – which is associated with the accumulation of tau protein.
This model provides an early biomarker of impending brain decline, which could guide future prevention and treatment.
The paper also shows for the first time that sleep medications known as dual orexin receptor antagonists — commonly used to treat insomnia, or difficulty falling asleep and staying asleep — can significantly reduce REM sleep behavior disorder.
Current therapeutic options for this condition are mainly 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 the ways sleep quality declines as neurodegeneration progresses and whether there are ways to mitigate such changes,” said corresponding author Andrew W. Varga, MD, Ph.D., associate professor of medicine (Pulmonary , Critical Care and Sleep Medicine) at Icahn School of Medicine at Mount Sinai.
“We identify a new model in which REM sleep behavior disorder can arise, due to neurodegeneration associated with tau protein accumulation, and a new therapy that could minimize REM sleep behavior disorder.”
Mount Sinai researchers used a mouse model to study neurodegenerative disorders by examining the brain after 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), sleep duration, transitions from wakefulness to sleep, and how some factors are related to age.
Nearly one-third of the older subjects exhibited dream-actualizing behaviors reminiscent of REM sleep behavior disorder, including chewing and extremity stretching.
After administering a dual orexin receptor antagonist twice over a 24-hour period to evaluate sleep in light and dark phases, the researchers noted that the medication not only reduced the time it took to fall asleep and both the quality as sleep duration increased, but also decreased levels of dream performance.
Researchers hope their findings will encourage future trials of dual orexin receptor antagonists to treat REM sleep behavior disorder in humans, as the medication is already FDA-approved and available to treat people with insomnia.
“We expected a deterioration in sleep quality with progressive neurodegeneration related to tau accumulation, but the observation of dream performance was a surprise,” said lead author Korey Kam, Ph.D., assistant professor of medicine (Pulmonary, Critical Care and Sleep Medicine) at Icahn’s Mount Sinai.
“It was even more surprising and exciting to see that a dual orexin receptor antagonist could significantly minimize the dream-execution behavior.”
About this sleep research news
Author: Andrew W. Varga
Source: Mount Sinai Hospital
Contact: Andrew W. Varga – Mount Sinai Hospital
Image: The image is credited to Neuroscience News
Original research: Closed access.
“Effect of aging and a dual orexin receptor antagonist on sleep architecture and NREM oscillations, including a REM behavior disorder phenotype in the PS19 mouse model of tauopathy” by Andrew W. Varga et al. Journal of Neuroscience
Effect of aging and a dual orexin receptor antagonist on sleep architecture and NREM oscillations, including a REM behavior disorder phenotype in the PS19 mouse model of tauopathy
The impact of tau pathology on sleep microarchitecture features, including slow oscillations, spindles and their coupling, has been understudied, despite the proposed importance of these electrophysiological features for learning and memory. Dual orexin receptor antagonists (DORAs) are known to promote sleep, but whether and how they affect sleep microarchitecture in the setting of tauopathy is unknown.
In the PS19 mouse model of tauopathy (MAPT P301S, both male and female), young PS19 mice aged 2-3 months show a sleep electrophysiological signature with markedly reduced spindle duration and strength and increased slow oscillation (SO) density in comparison with littermate controls, even though there is no significant tau hyperphosphorylation, tangle formation, or neurodegeneration at this age.
With age, there is evidence for sleep disruption in PS19 mice, characterized by decreased REM duration, increased non-REM and REM fragmentation and more frequent brief arousal at the macro level, and decreased spindle density, SO density, and spindle-SO coupling at micro level. In ∼33% of old PS19 mice, we observed unexpectedly abnormal goal-directed behaviors in REM, including chewing, paw grasping, and forelimb/hindlimb extension, seemingly consistent with REM behavior disorder (RBD).
Oral administration of DORA-12 in elderly PS19 mice increased non-REM and REM duration, albeit with shorter periods, and increased spindle density, spindle duration, and SO density with no change in spindle-SO coupling, strength in the SO or spindle tapes or the excitement index.
We observed a significant effect of DORA-12 on objective measures of RBD, encouraging future research on DORA effects on sleep-mediated cognition and RBD treatment.