SRI Scientists Uncover Potential New Treatment For Narcolepsy

Neuroscientists at SRI International have discovered that a form of baclofen, used to treat muscle spasticity, is a better treatment for narcolepsy than the best drug available in the market when tested in mice models.

Narcolepsy is a chronic neurologic disorder characterized by excessive sleepiness during daytime hours. The disorder is not a rare condition but is typically under-recognized and under-diagnosed. Narcolepsy affects approximately 1 in 2,000 people worldwide.

The scientists developed a new mouse model of narcolepsy along with a standard model to investigate a novel therapeutic pathway and determine a promising approach in the treatment of the condition. In humans, the disorder typically sets during adolescence or later. An existing model of narcolepsy called “Ataxin mice” has been used for the past decade to study narcolepsy, however the study has been hampered by a significant limitation: the mice are born with the deficiency of the neurotransmitter hypocretin implicated in narcolepsy, while humans often develop narcolepsy 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 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, program director at the National Institute of Neurological Disorders and Stroke (NINDS) under the National Institutes of Health.

Thomas Kilduff, Director of the Center for Neuroscience within SRI Biosciences, and colleagues used the new model and the Ataxin model to compare R-baclofen against gamma-hydroxybutyrate (GHB). R-baclofen is one of the two isomers that comprise the chemical compound mixture baclofen. Sodium oxybate, the sodium salt of GHB, received approval from the FDA in 2002 as the only therapeutic for narcolepsy that offered relief from excessive daytime sleepiness and sleep disruption.

The team discovered that R-baclofen promoted sleep time and wakefulness during appropriate times for the mice models. GHB increased sleep intensity at a lesser level but failed to improve narcolepsy symptoms to the extent that R-baclofen did. “R-Baclofen works better than GHB in these two mouse models, but it remains to be determined whether it will work better in humans. Although baclofen is already known to be safe for use in humans, the dose that is effective for spasticity may be different than the dose of R-baclofen that has the potential to treat narcolepsy,” said Kilduff.