Tori Shaeffer

Development of a Novel GABA-A Agonist in Fragile X Syndrome

Of the many genes known to be regulated by FMRP, the gamma-aminobutyric acid receptor A (GABA(A)), is gaining attention as a potential target for the treatment of FXS. Mounting evidence suggests decreased expression and functioning of GABA(A) is involved in the pathophysiology of FXS. Non-selective GABA(A) agonism in animal models of FXS has been associated with normalization of morphological features, GABA(A) expression, and behavior. However, the clinical use of these agents in fragile X is associated with unwanted side-effects, such as sedation, dulling of cognition, and occasional paradoxical agitation, which limits their use. Given the limitations in available GABA(A)-based treatment of FXS, this group plans to investigate a novel selective GABA(A) agonist in a mouse model of FXS. This agent has the potential to relieve many symptoms of fragile X without the unwanted side effects.