Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr;27(4):389-406.
doi: 10.1080/13543784.2018.1459561. Epub 2018 Apr 9.

An Overview of Hypocretin Based Therapy in Narcolepsy


An Overview of Hypocretin Based Therapy in Narcolepsy

Shinichi Takenoshita et al. Expert Opin Investig Drugs. .


Introduction: Narcolepsy with cataplexy is most commonly caused by a loss of hypocretin/orexin peptide-producing neurons in the hypothalamus (i.e., Narcolepsy Type 1). Since hypocretin deficiency is assumed to be the main cause of narcoleptic symptoms, hypocretin replacement will be the most essential treatment for narcolepsy. Unfortunately, this option is still not available clinically. There are many potential approaches to replace hypocretin in the brain for narcolepsy such as intranasal administration of hypocretin peptides, developing small molecule hypocretin receptor agonists, hypocretin neuronal transplantation, transforming hypocretin stem cells into hypothalamic neurons, and hypocretin gene therapy. Together with these options, immunotherapy treatments to prevent hypocretin neuronal death should also be developed.

Areas covered: In this review, we overview the pathophysiology of narcolepsy and the current and emerging treatments of narcolepsy especially focusing on hypocretin receptor based treatments.

Expert opinion: Among hypocretin replacement strategies, developing non-peptide hypocretin receptor agonists is currently the most encouraging since systemic administration of a newly synthesized, selective hypocretin receptor 2 agonist (YNT-185) has been shown to ameliorate symptoms of narcolepsy in murine models. If this option is effective in humans, hypocretin cell transplants or gene therapy technology may become realistic in the future.

Keywords: Narcolepsy type1; cataplexy; hypocretin; narcolepsy type2; orexin; sleepiness.

Similar articles

See all similar articles

Cited by 7 articles

See all "Cited by" articles

Supplementary concepts

LinkOut - more resources