The principal goal of this revised proposal is to establish a blood hypocretin measure for a diagnostic test for human narcolepsy. Narcolepsy is a debilitating sleep disorder that affects 1 in 2000 U.S. citizens. Although the onset of the disease most typically occurs in adolescence, the diagnosis is often delayed by up to 10 years from the disease onset. This is mainly due to the fact that no specific diagnostic tool of narcolepsy is currently available. We have discovered that hypocretin levels are undetectably low in the cerebrospinal fluid (CSF) of most patients with narcolepsy-cataplexy. Considering the fact that genetic ablations of the hypocretin ligand and receptors induce narcolepsy in animals, deficits in hypocretin neurotransmission is likely to be the major pathophysiology of most human narcolepsy. Undetectably low CSF hypocretin levels are very specific for narcolepsy among various sleep and neurological disorders, and CSF hypocretin measures are now included as a positive diagnosis of narcolepsy-cataplexy in the 2nd revision of International Classification of Sleep Disorders (ICSD). Although many patients will likely receive benefits from this new diagnostic test, development of less invasive-methods, such as blood testing would be ideal, especially at outpatient sleep clinics. Our preliminary results suggest that hypocretin can be detected in the plasma of healthy subjects, but may be absent in narcoleptic subjects. We therefore will evaluate whether plasma measurement can be used as an alternative diagnostic tool for narcolepsy. We will focus on the validation of the plasma assay as well as the development of more sensitive assays for plasma measurement. If this is successfully achieved, central hypocretin deficiency can be tested for at sleep clinics by a routine blood test.

Public Health Relevance

Narcolepsy is a debilitating disorder that affects 1 in 2000 U.S. citizens. Our preliminary results suggest that hypocretin can be detected in the plasma of healthy subjects, but may be absent in narcoleptic subjects. We will therefore evaluate whether a plasma measurement can be used as an alternative diagnostic tool for the treatment of narcolepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH078103-02
Application #
7564059
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
2008-02-05
Project End
2010-11-30
Budget Start
2008-12-01
Budget End
2010-11-30
Support Year
2
Fiscal Year
2009
Total Cost
$187,625
Indirect Cost
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305