Molecular genetics and treatment of narcolepsy.

Abstract

Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy. The hypocretin/orexin deficiency is likely to be the key to its pathophysiology in most of cases although the cause of human narcolepsy remains elusive. Acting on a specific genetic background, an autoimmune process targeting hypocretin neurons in response to yet unknown environmental factors is the most probable hypothesis in most cases of human narcolepsy with cataplexy. Although narcolepsy presents one of the tightest associations with a specific human leukocyte antigen (HLA) (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility. In addition to a point mutation in the prepro-hypocretin gene discovered in an atypical case, a few polymorphisms in monoaminergic and immune-related genes have been reported associated with narcolepsy. The treatment of narcolepsy has evolved significantly over the last few years. Available treatments include stimulants for hypersomnia with the quite recent widespread use of modafinil, antidepressants for cataplexy, and gamma-hydroxybutyrate for both symptoms. Recent pilot open trials with intravenous immunoglobulins appear an effective treatment of cataplexy if applied at early stages of narcolepsy. Finally, the discovery of hypocretin deficiency might open up new treatment perspectives.

• Authors: Yves Dauvilliers, Mehdi Tafti
• Journal: Annals of medicine (Ann Med) Vol. 38 Issue 4 Pg. 252-62 ( 2006) ISSN: 0785-3890 [Print] England
• PMID: 16754256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antidepressive Agents, Tricyclic
• Benzhydryl Compounds
• Central Nervous System Stimulants
• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• Immunoglobulins, Intravenous
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• Neuropeptides
• Orexin Receptors
• Orexins
• Receptors, G-Protein-Coupled
• Receptors, Neuropeptide
• Sodium Oxybate
• Catechol O-Methyltransferase
• Clomipramine
• Modafinil

Topics

• Animals
• Antidepressive Agents, Tricyclic (therapeutic use)
• Benzhydryl Compounds (therapeutic use)
• Catechol O-Methyltransferase (genetics)
• Central Nervous System Stimulants (therapeutic use)
• Clomipramine (therapeutic use)
• Genetic Predisposition to Disease
• HLA-DQ Antigens (genetics)
• HLA-DQ beta-Chains
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Intracellular Signaling Peptides and Proteins (genetics)
• Membrane Glycoproteins (genetics)
• Modafinil
• Molecular Biology (trends)
• Narcolepsy (cerebrospinal fluid, drug therapy, genetics)
• Neuropeptides (genetics)
• Orexin Receptors
• Orexins
• Polymorphism, Genetic
• Randomized Controlled Trials as Topic
• Receptors, G-Protein-Coupled (deficiency)
• Receptors, Neuropeptide (deficiency)
• Sodium Oxybate (therapeutic use)