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Sleep researchers at SRI International identify promising new treatment for narcolepsy
Date:5/7/2014

rugs that only address the symptoms, rather than the underlying causes, of narcolepsy.

In the first of the two papers, "Conditional Ablation of Orexin/Hypocretin Neurons: A New Mouse Model for the Study of Narcolepsy and Orexin System Function," Kilduff and Black teamed with colleagues at five institutions in Japan to generate a model of narcolepsy that better mimics the human disorder. The existing model, called "Ataxin mice," has been available for over 10 years. Although Ataxin mice have enabled researchers to study narcolepsy, an important limitation is that these mice are born with the deficiency of the neurotransmitter hypocretin that has been implicated in causing narcolepsy, whereas the onset of human narcolepsy typically occurs after puberty.

"The mouse model developed by Dr. Kilduff and his colleagues offers a new approach to study narcolepsy and to explore potential therapies for this devastating sleep disorder. This new model allows more precise control of the timing and extent of hypocretin/orexin neuron loss, and thus may better mimic human narcolepsy," said Janet He, Ph.D., program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

In collaboration with Professor Akihiro Yamanaka of Nagoya University in Japan, formerly an SRI International Fellow in Dr. Kilduff's laboratory, the research team genetically engineered a mouse in which the hypocretin neurons could be selectively eliminated at any age simply by removal of an antibiotic in the mouse food. In the new "DTA" model, degeneration of hypocretin neurons can be initiated after puberty, causing the mice to exhibit the two major symptoms of narcolepsy: excessive daytime sleepiness and cataplexy, the brief loss of muscle tone experienced by most narcoleptics.

In the second paper, "GABAB Agonism Promotes Sleep and Reduces Cataplexy in Murine Narcolepsy," Black, Kilduff and colleagues used the ne
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Contact: Dina Basin
dina.basin@sri.com
650-859-3845
SRI International
Source:Eurekalert

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