Wake-ALS

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. It is characterized by progressive paralysis, appearing around age 60 and progressing to death within 2 to 5 years. ALS has long been considered a disease affecting only cortical and spinal motor neurons. However, recent work clearly demonstrates that it is a neurodegenerative disease affecting the central nervous system globally, and non-motor symptoms predict the severity and survival of patients. Our previous work has shown the existence of significant defects in the sleep-wake cycle, in early-onset patients, but also in asymptomatic carriers of mutations associated with ALS as well as in animal models. Our data also show that pharmacological intervention on MCH and orexin neurons prevents these sleep defects in animal models. From these preliminary results, we hypothesize that alterations in the sleep-wake cycle contribute to different ALS symptoms, metabolic, cognitive and motor which characterize the disease and its severity. To address this hypothesis, we will systematically characterize the wake and sleep circuits in ALS and their contribution to non-motor symptoms, but also to the triggering of motor symptoms. Our consortium includes teams with the essential expertise to carry out the project, with strong expertise in ALS (L. Dupuis, France) and complementary expertise in sleep physiology and pathology and functional neuroanatomy (P.H. Luppi, France) thus providing an ideal combination to achieve our objectives. The completion of this project will provide a better understanding of the role of early alterations in brain functioning in the course of ALS, and could lead to therapeutic strategies targeting sleep alterations in ALS.