Hormone Therapies Show Promise for Sleep Disorders in ALS

A groundbreaking study has revealed new insights into sleep disturbances associated with amyotrophic lateral sclerosis (ALS) and identified potential hormone-based treatments. The research, conducted by scientists from the University of Strasbourg and the University Hospital of Ulm, marks a significant step forward in understanding and potentially managing sleep-related symptoms in ALS patients.

Early-Stage Sleep Disruptions in ALS

The study, published in Science Translational Medicine on January 29, 2025, confirms that sleep alterations are an early phenomenon in ALS, preceding both respiratory impairment and motor symptoms. Researchers analyzed sleep patterns in early-stage ALS patients without respiratory issues and individuals carrying ALS-risk genes but not yet symptomatic. Both groups exhibited disrupted sleep, suggesting that these disturbances are intrinsic to the disease process rather than secondary effects of advanced symptoms.

Promising Hormone Therapies

Two hormone-based approaches showed potential in addressing sleep disruptions in ALS mouse models:

1. Suvorexant, an FDA-approved insomnia drug marketed as Belsomra by Merck & Co., effectively decreased wakefulness and increased REM sleep. This orexin/hypocretin (ORX) neuron inhibitor also normalized non-REM sleep patterns.

2. Melanin-concentrating hormone (MCH), when injected into cerebrospinal fluid, improved sleep and demonstrated a protective effect on motor neurons in the spine. This unexpected finding suggests a possible link between sleep regulation and the progression of ALS motor symptoms.

Implications for ALS Research and Treatment

The identification of sleep disturbances as an early marker of ALS opens new avenues for diagnosis and treatment. The protective effect of MCH on motor neurons is particularly intriguing, hinting at a potential connection between sleep regulation and the characteristic motor symptoms of ALS.

The study's authors emphasize the need for further research, stating, "Further preclinical and clinical research is warranted to investigate the impact of defects in sleep and sleep regulatory neuropeptides on cognitive deficits, weight loss, or motor symptom progression associated with ALS."

As the pharmaceutical industry continues to seek effective treatments for neurodegenerative diseases, these findings offer promising leads for developing targeted therapies that may address both sleep disturbances and underlying disease mechanisms in ALS.