Results of a preliminary study in this week's issue of THE LANCET suggest a step forward in our understanding of the processes behind narcolepsy; there appears to be an underlying autoimmune process for people with a certain genetic profile. Future diagnostic testing of people with this profile should lead to substantial improvements in disease treatment.
Narcolepsy is a chronic disabling sleep-wake disorder characterised by excessive daytime sleepiness, which is caused by changes in hormone concentrations and nervous system activity. Tom Gordon (Flinders University, South Australia) and colleagues induced narcolepsy-like symptoms in smooth muscles of mice by injecting antibodies from blood samples of 9 people with confirmed narcolepsy. Mice injected with antibodies from 9 people who did not have narcolepsy (the control group) did not develop such symptoms.
Professor Gordon comments: "Our findings suggest that the functional autoantibody is a sensitive and specific marker for human narcolepsy and might lead to a clinically useful assay for diagnosing narcolepsy… Identification of the target of the autoantibody and a better understanding of its long-term effects could open up new possibilities for diagnosis and management of this disabling disease."
In an accompanying commentary (p 2076), Merrill S Wise (Baylor College of Medicine, Houston, USA, concludes: "If these preliminary findings are replicated with larger numbers of narcolepsy patients and appropriately selected healthy and diseased controls…[this study] will have opened an exciting new chapter in the narcolepsy story. The investigators might have identified the missing link that connects an autoimmune process to selective loss of hypocretin neurons and the development of narcolepsy. A clinically useful assay could lead to earlier diagnosis and improve the likelihood for effective use of immunomodulators, hypocretin agonists, or perhaps a preventive strategy before loss of hypocretin neurons below a critical threshold.
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