Tori Schaefer, PhD — Cincinnati Children’s Hospital

Development of a Novel GABA(A) a2,3 Agonist in Fragile X Syndrome

withTori Shaeffer
Craig Erickson, MD, Consultant

FRAXA Awards:
$21,000 in 2013

SUMMARY:
Dr. Schaeffer used this 2013 grant from FRAXA Research Foundation to analyze an investigational new compound that targets the GABA-A receptor. This study has led to a clinical trial of the compound, led by Dr. Craig Erickson at Cincinnati Children’s Hospital.

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.