Recent advances in treatment for narcolepsy

• Published in: Therapeutic Advances in Neurological Disorders Vol. 12; p. 1756286419875622
• Main Authors: Barateau, Lucie, Dauvilliers, Yves
• Format: Book Review Journal Article
• Language: English
• Published: London, England SAGE Publications 2019; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Amphetamines; Cataplexy; Children; Clinical trials; Cognitive science; Dopamine receptors; Drug development; Etiology; Histamine H3 receptors; Human health and pathology; Inverse agonists; Life Sciences; Methylphenidate; Modafinil; Narcolepsy; Neurons; Neurons and Cognition; Neurotrophin 1; Neurotrophin 2; Norepinephrine; Orexins; Patients; Phenylalanine; Precision medicine; REM sleep; Review; Sleep; Sleep and wakefulness; Sleep disorders; Sodium; cataplexy; hypocretin/orexin; sleepiness; narcolepsy type 1; immune-based therapies; narcolepsy type 2
• ISSN: 1756-2864; 1756-2856; 1756-2864
• DOI: 10.1177/1756286419875622

Narcolepsy type 1 (NT1) is a chronic orphan disorder, caused by the selective and irreversible loss of hypocretin/orexin (ORX) neurons, by a probable autoimmune process. Little is known about NT2 etiology and prevalence, sharing with NT1 excessive daytime sleepiness (EDS) and dysregulation of rapid eye movement (REM) sleep, but without cataplexy and loss of ORX neurons. Despite major advances in our understanding of the neurobiological basis of NT1, management remains nowadays only symptomatic. The main and most disabling symptom, EDS, is managed with psychostimulants, as modafinil/armodafinil, methylphenidate, or amphetamines as a third-line therapy. Narcolepsy is an active area for drug development, and new wake-promoting agents have been developed over the past years. Pitolisant, a selective histamine H3 receptor inverse agonist, has been recently approved to treat patients with NT1 and NT2. Solriamfetol, a phenylalanine derivative with dopaminergic and noradrenergic activity will be soon a new therapeutic option to treat EDS in NT1 and NT2. Sodium oxybate, used for decades in adult patients with narcolepsy, was recently shown to be effective and safe in childhood narcolepsy. The discovery of ORX deficiency in NT1 opened new therapeutic options oriented towards ORX-based therapies, especially nonpeptide ORX receptor agonists that are currently under development. In addition, immune-based therapies administered as early as possible after disease onset could theoretically slow down or stop the destruction of ORX neurons in some selected patients. Further well-designed controlled trials are required to determine if they could really impact on the natural history of the disease. Given the different clinical, biological and genetic profiles, narcolepsy may provide a nice example for developing personalized medicine in orphan diseases, that could ultimately aid in similar research and clinical efforts for other conditions.