Dual Hormone Therapies Normalize Sleep Patterns in ALS Mouse Models

Sleep disturbances are early symptoms in ALS patients and presymptomatic gene carriers, characterized by increased wakefulness and decreased non-rapid eye movement (NREM) sleep14.

Two mouse models of ALS (SOD1G86R and FusΔNLS/+) exhibited similar sleep alterations, including increased wake time and decreased NREM and REM sleep4.

Intracerebroventricular administration of melanin-concentrating hormone (MCH) partially rescued sleep alterations in ALS mouse models, fully restoring REM sleep but exacerbating NREM sleep deficits4.

Oral administration of suvorexant, a dual orexin receptor antagonist, fully normalized sleep patterns in both ALS mouse models, restoring wake, REM, and NREM sleep to levels similar to wild-type animals4.

The study suggests that sleep alterations in ALS are primarily driven by imbalances in MCH and orexin signaling in the lateral hypothalamus14.

These findings indicate that targeting sleep-regulating hormones could be a potential therapeutic approach for addressing sleep disturbances in ALS patients410.

Sources:

1. https://www.medrxiv.org/content/10.1101/2024.08.21.24312343v1

4. https://www.medrxiv.org/content/10.1101/2024.08.21.24312343v1.full

10. https://www.fiercebiotech.com/research/two-hormone-therapies-restore-normal-sleep-mouse-models-amyotrophic-lateral-sclerosis