This is a proposal to establish a research center on narcolepsy and related disorders. Its purpose is to bring together a multidisciplinary group of investigators who will conduct research into the etiology, pathogenesis, diagnosis, prevention, and treatment of narcolepsy -- a neurogenetic disorder of sleep processes afflicting more than 250,000 persons in the United States. Disorders of excessive daytime sleepiness which do not fit the exact criteria for narcolepsy and afflict an additional large group of individuals, will also be at issue. The initiating concept is that scientific methodologies now routinely available for research on other medical and neurological problems will be brought to bear simultaneously and cooperatively in one place on a primary sleep pathology. The Center will have core facilities and research projects: For the latter, we propose a molecular genetic study of human and canine narcolepsy utilizng restriction fragment length polymorphism studies and DNA sequencing. Another project proposes experiments to test the autoimmune basis for narcolepsy. An autoimmune mechanism is strongly suggested by the high association of HLA-DR2 antigen and the narcolepsy phenotype, an association which is present in many other autoimmune diseases. A third project involves neurochemistry and rests on the foundation of prior findings showing regional abnormalities in catecholamines and neurotransmitter receptors in the central nervous system of the narcoleptic dog. The fourth project involves the refinement of the diagnosis of non-respiratory disorders of excessive daytime sleepiness, of which narcolepsy and CNS hypersomnia are the major categories. It will study the role of the HLA system through typing studies coupled with clinical evaluation and family studies. The fifth major project involves observations on sleep/wake behavior during adolescence in high-risk children, e.g. children who have a parent with narcolepsy. Finally, in order to accelerate research on narcolepsy and related disorders, we propose four special pilot projects in several promising new areas.
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