A functional autoantibody in human narcolepsy: direct evidence for the autoimmune hypothesis [ 2006 - 2009 ]

Research Grant

Researchers: Prof Thomas Gordon (Principal investigator) ,  Prof R. Douglas Mcevoy

Brief description Narcolepsy is a chronic disabling sleep disorder causing irresistible sleepiness and, in most cases, brief attacks of weakness on emotional arousal (cataplexy). Other symptoms include a transient paralysis at the beginning or end of sleep and vivid hallucinations at the start of sleep. Symptoms usually appear during adolescence or early adulthood. It affects between one in 1,000 and one in 2,000 people, yet the diagnosis is often delayed for several years because of the lack of a simple diagnostic marker. It has been suspected for some time that narcolepsy is caused by a malfunctioning immune system, but direct evidence for the so-called autoimmune hypothesis has been lacking. We have recently discovered the smoking gun in the form of an autoantibody that circulates in the bloodstream and produces some of the features of narcolepsy on transfer to experimental animals. The identification of the autoantibody, which we term a functional autoantibody because it directly alters the function of nerves thought to be involved in narcolepsy and cataplexy, opens a new chapter in narcolepsy research that has important diagnostic and therapeutic implications. Testing for the autoantibody in subjects recruited from national and international centres for sleep research will determine its value in the diagnosis of narcolepsy and may help distinguish narcolepsy from other sleep disorders. Preliminary findings are encouraging and suggest that the autoantibody is a sensitive and specific marker for human narcolepsy and might lead to a clinically useful diagnostic test. In another part of the project, experimental approaches willl be used to identify an antibody called an antiidiotype that can neutralise the narcolepsy autoantibody and therefore be developed as a therapeutic agent. Finally, experiments have been designed to examine the effect of the autoantibody on neurotransmitters in the brain that are believed to result in cataplexy.

Funding Amount $AUD 444,928.85

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant