Mignot and Yanagisawa Awarded Lasker Prize for Orexin Discovery in Wake, Sleep, and Narcolepsy

Narcolepsy is a chronic neurological disorder characterized by overwhelming daytime sleepiness and often cataplexy, significantly impairing quality of life. Historically, the precise neurochemical mechanisms underlying sleep-wake regulation and the pathophysiology of narcolepsy were poorly understood, leading to symptomatic but often inadequate treatments. The identification of a specific system responsible for maintaining wakefulness was a critical unmet need, paving the way for targeted therapeutic interventions. The orexin (also known as hypocretin) system emerged as a pivotal player in this complex biological process.

This paper commemorates the independent, yet converging, discoveries by Mignot and Yanagisawa. Mignot's group used a genetic approach, identifying a mutation in the orexin receptor 2 (HCRTR2) gene as the cause of canine narcolepsy. Concurrently, Yanagisawa's team employed reverse pharmacology, isolating novel neuropeptides from rat brains, named orexin A and orexin B. They then identified the corresponding G-protein coupled receptors, orexin receptor 1 (HCRTR1) and orexin receptor 2 (HCRTR2), establishing the complete orexin system.