Narcolepsy is a rare, chronic neurological disorder characterized primarily by excessive daytime sleepiness, disrupted nighttime sleep, and abnormal transitions between the state of sleep and wakefulness.
This review looked at the animal models of narcolepsy and how they provided important insights into the disease, particularly by demonstrating the critical role of the hypocretin-system, which is also called the orexin system.
Orexin regulates wakefulness through OX1 and OX2 receptors. The authors review how animal studies—particularly in dogs and mice—contributed to the discovery of orexin deficiency in people with narcolepsy, which influenced diagnostic criteria and directed research toward orexin-related drug development. The differences seen between animal models and humans, including possible causes, drug pharmacokinetics, and circadian biology, lead to differences in research findings and treatment responses.
Our saporin conjugate, Orexin-SAP, was included in this review because it was used to lesion the lateral hypothalamus which produced many of the phenotypes associated with narcolepsy.
There are still significant challenges that remain in treating symptoms beyond the excessive daytime sleepiness and cataplexy, which indicates there is still a need for broader therapeutic approaches.
Looking to the future, with reports that the narcolepsy therapeutics market will continue growing, there will be the need to identify new drug targets and developing diurnal animal models that more closely reflect the human sleep-wake cycle.
