Treatment of Fragile X Syndrome via Dopamine Enhancers and Glutamate Inhibitors
with Patricia Cogram, PhD
$50,000 in 2011
$50,000 in 2010
by Justin Cowan, 4/1/2010
Dopamine Enhancers and Glutamate Inhibitors
This project aims to follow up our and others observations that the dopamine receptor is under expressed in the fragile X syndrome and thus determine the effectiveness of targeted pharmacological treatments in fragile X syndrome. We hope to increase our understanding of the mechanism of under expression of dopamine in fmr1 knockout mice and to test whether drugs that activate dopamine release and glutamate inhibition can alleviate the clinical symptoms of fragile X syndrome.
For the purpose of this project, we are investigating two compounds, Safinamide and Kuvan (BH4). We are using human cortical cells fmr1-/- to analyze the direct effects of these compounds on the neuronal phenotype and also to help us understanding the role of Safinamide and Kuvan in regulating dopamine signaling and glutamate inhibition. We will also evaluate changes in synaptic plasticity in fmr1 knockout mice, as measured by long-term potentiation with electrophysiological methods. Lastly, we will develop novel sensitive behavioral phenotyping tests for the fmr1 knock-out mouse and evaluate the treatment effects of Safinamide and Kuvan on mouse behaviors.
The FRAXA project will be principally conducted at our Center for the Investigation of Fragile X Syndrome (CiX-Fra), a recently established clinical and research center based at the University of Chile, Santiago, Chile. Our group is engaged in multidisciplinary research and research training on the pathogenesis and treatment of fragile X syndrome, from genes to cognition, using several models including the fly, the fish, the mouse, and also our patient population.