Genomic Analysis in Narcolepsy-Cataplexy

Investigator: Neil J. Risch, PhD
Sponsor: Stanford University

Location(s): United States


Narcolepsy is a frequent and disabling neurological disorder affecting more than 1 in 2,000 Americans. Our recent findings have led to new diagnostic procedures but have not yet changed therapeutic options. Our aims are improved diagnosis, a better understanding of the narcolepsy pathophysiology and the discovery of new treatments, if not a cure for narcoleptic patients. To support this research proposal, five main core activities are recognized: 1) A research administrative and coordinating function to facilitate the research & interactions among investigators and projects 2) Management of the Stanford University Center for Narcolepsy animal colonies used in this proposal; this includes zebrafish, mice, and rats. 3) Recruitment of human narcolepsy patients for research projects: this includes the banking of DNA, serum, cerebrospinal fluid and brain specimens from narcolepsy and control subjects. 4) Maintenance of computerized databases containing human, mouse/rat, canine narcolepsy data and tissue sample data; maintenance of the project's website and data-sharing on-line. 5) Maintenance of all documentation supporting adherence to all federal guidelines and policies for conducting research. It is the responsibility of the Principal Investigator to assure that the Center for Narcolepsy scientists work as an integrated team. His direction and scientific leadership, is essential to the pursuit of the overall goals of the program. A weekly research meeting is held to facilitate communication among the investigators and between the research staff and research administration staff.

This study has four projects and a core (Project A). The core (Project A) provides the necessary core resources to support research projects at the Stanford Center for Narcolepsy, most notably biological samples. The goal of Project B, directed by Dr. Terry Young at the University of Wisconsin, Madison is to determine the prevalence of narcolepsy without cataplexy using an epidemiological approach and to study its association with HLA and lypocretin deficiency. Project D, directed by Dr. Juliette Faraco, will use a zebrafish model to isolate novel genes regulating hypocretin and histamine neurotransmission. In Project F, directed by Dr. Luis de Lecea, the discoverer of hypocretins, is seeking to identify novel genes with preferential expression in hypocretin-containing cells; an accessory goal of this project will be to study the neuropathology of narcolepsy without cataplexy. Project E, directed by Dr. Joachim Hallmayer, will use a human genetic approach to identify novel narcolepsy susceptibility genes.