The pathogenesis of narcolepsy, current treatments and prospective therapeutic targets

Abstract

Introduction: Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness (EDS), cataplexy and abnormal manifestations of rapid eye movement (REM) sleep such as sleep paralysis and hypnagogic hallucinations. Recent studies have demonstrated that narcolepsy–cataplexy is caused by the postnatal loss of hypocretin neurons (Type 1 narcolepsy), possibly because of autoimmune mechanisms. Although several new therapeutic options have recently been introduced, these new findings have not yet been incorporated to the therapies.

Areas covered: In this review, we first describe clinical symptoms and pathogenesis of narcolepsy. Second, we summarize the current knowledge about pharmacological treatments of narcolepsy and the modes of action of each drug. Finally, we discuss prospective therapeutic targets for narcolepsy.

Expert opinion: Current treatments are mostly symptomatic, but it is necessary to initiate the appropriate pharmacological treatment for each symptom with the understanding of pharmacological mechanisms. Development of synthetic hypocretin receptor agonists is the first and most urgent step for the improved treatment of Type 1 narcolepsy. Successes in this step will likely lead to developments of cell transplantation and gene therapies.

Keywords:

• amphetamine
• antidepressants
• cataplexy
• gamma-hydroxybutyrate
• hypnogogic hallucinations
• modafinil
• Narcolepsy
• sleep paralysis
• sodium oxybate
• stimulants