Current and future therapeutic approaches in narcolepsy

Abstract

Narcolepsy with cataplexy (NC) is a disabling orphan sleep disorder characterized by excessive daytime sleepiness, cataplexy and other dissociated manifestations of rapid eye movement sleep (hypnagogic hallucinations and sleep paralysis), as well as frequent movement and awakening during night-time sleep. In this article, we will describe the main symptoms and the current and future treatments of NC. Pathophysiological studies have shown that NC is caused by the early loss of neurons in the hypothalamus that produce hypocretin/orexin, a wakefulness-associated neurotransmitter present in cerebrospinal fluid. The cause of neural loss could be autoimmune since most patients have the human leukocyte antigen DQB1*0602 allele that predisposes individuals to NC. The treatment of narcolepsy has evolved over the past few years with the widespread use of modafinil for daytime sleepiness, antidepressants for cataplexy and γ-hydroxybutyrate (sodium oxybate) for both symptoms. Potential development of new wake-promoting drugs, anticataplectic medications, slow-wave sleep-enhancing treatments, hypocretin-replacement therapy and immunotherapy at early stages of the disease needs to be evaluated in the near future.