Trouble sleeping is common in other neurodegenerative diseases, but past research has only suggested that it occurs in patients with amyotrophic lateral sclerosis. Now, a new study has not only confirmed that sleep disruption is a symptom of ALS but has identified two potential hormone therapies that could treat it.
In mouse models of ALS, the approved drug suvorexant and melanin-concentrating hormone were both able to decrease time awake and increase REM sleep. Suvorexant was also able to normalize non-REM sleep, while MCH did not.
The study was led by researchers from the University of Strasbourg in France and the University Hospital of Ulm in Germany. The results were published in Science Translational Medicine on January 29.
While previous studies have found links between ALS and sleep disruptions, the authors wrote, that research was on advanced patients whose respiratory symptoms may have been causing the sleep problems rather than the disease itself. ALS causes progressive nerve degeneration that leads to muscle weakness, difficulty swallowing and breathing, and eventually, death.
In the new study, researchers analyzed the sleep of patients in the early stages of ALS who don’t yet have respiratory impairment, as well as people who carry genes that increase the risk of ALS but who don’t have the disease. They found that both early-stage and presymptomatic patients had disrupted sleep, confirming that “sleep alterations are an early phenomenon in ALS that precedes respiratory impairment and even motor symptoms,” the authors wrote.
Because two types of neurons known to be involved in sleep regulation, MCH neurons and orexin/hypocretin (ORX) neurons, are degraded in ALS, the researchers tested therapies targeting them in mice with the disease.
Inhibiting ORX neurons with suvorexant, sold by Merck & Co. as Belsomra for insomnia, suppressed their known function in promoting wakefulness, the authors reported. Injecting MCH into the cerebrospinal fluid not only improved sleep but also reduced the loss of motor neurons in the spine.
The protective effect that MCH has on motor neurons suggests a link between sleep disruption and ALS’ characteristic motor symptoms, the authors suggest.
“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,” they wrote.