Discovery of Novel Therapeutics for Disordered Sleep in Fragile X Syndrome

Project: Research project

Project Details


Discovery of Novel Therapeutics for Disordered Sleep in Fragile X Syndrome

PRMRP Topic Area: Fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited form of mental retardation. Individuals affected by Fragile X also exhibit disruptions in the duration, quality and timing of sleep. The gene responsible for FXS, FMR, is highly conserved in animal models including the fruit fly and the mouse. Importantly, genetic inactivation of FMR genes in flies and mice also disrupt circadian (~24 h) rhythms and sleep. Studies on Fragile X animal models have led to the development of novel drugs that effectively can treat cognitive deficits. However, these compounds fail to cure circadian and sleep disruption. As a tool to discover novel treatments for disrupted sleep and circadian rhythms in those affected with Fragile X, we propose to use in vivo screening of FDA-approved or clinical drug libraries in the fruit fly. Remarkably, the genes important for circadian rhythms and sleep are similar between flies and humans. Indeed, drugs, that promote wake, such as caffeine, and those that promote sleep in humans, have similar effects on flies. Flies are inexpensive to handle, allowing screening of large numbers of organisms and enabling economical testing of large numbers of drugs in a short time. Importantly, circadian rhythms and sleep can be quantitatively, reproducibly, and inexpensively assessed on a large scale. Identification of drugs for efficacy and side effects in flies will be highly predictive for similar functions in higher systems including humans. The proposed studies provide an unbiased economical strategy to develop novel therapeutics for the treatment of Fragile X syndrome. As compounds to be screened have already past stringent FDA filters, identified effective compounds can more quickly be tested in FXS patients.
Effective start/end date9/1/182/28/21


  • U.S. Army Medical Research and Materiel Command (W81XWH1810594)


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