Narcolepsy Type I as an autoimmune disorder

Narcolepsy Type 1 (NT1) is hypothesized to be an autoimmune disease targeting the hypocretin/orexin neurons in the lateral hypothalamus. Ample genetic and epidemiologic evidence point in the direction of a pathogenesis involving the immune system. Many autoantibodies have been detected in blood samples from NT1 patients, but none in a consistent manner. Importantly, T cells directed toward hypocretin/orexin neurons have been detected in samples from NT1 patients. However, it remains to be seen if these potentially autoreactive T cells are also present in the hypothalamus and if they are pathogenic. For this reason, NT1 does still not fully meet the criteria for being classified as a genuine autoimmune disease, even though more and more results are pointing in that direction as will be described in this chapter. The autoimmune hypothesis has led to many attempts at slowing or stopping disease progression with immunomodulatory treatment, but so far the overall results have not been very encouraging. It is clear that more research into the pathogenesis of NT1 is needed to establish the precise role of the immune system in disease development.