Transcriptomic analysis of disease pathways in animal models of Tourette syndrome

Prof. Marco Bortolato, Department of Pharmacology & Toxicology
University of Kansas

Project dates: 2013-2014

Tourette syndrome (TS) is a neurodevelopmental disorder with marked male predominance (M:F=4:1). The disease is characterized by multiple motor and vocal tics, which have a disrupting impact on social and occupational functioning. The current available therapies for TS have variable efficacy and induce significant side effects, highlighting the need for novel treatment and diagnostic biomarkers that can predict treatment response.The objective of this pilot NIH/COBRE grant is to study the molecular bases of the gender differences in TS and the mechanisms of action of finasteride in this disease. Finasteride is the inhibitor of 5J-reductase (5AR), the enzyme catalyzing the conversion of testosterone and other steroid precursors into their neuroactive metabolites. Recent evidence from our group suggests that FIN may be a highly efficacious therapy for TS with limited side effects.

The proposed studies will be focused on transcriptomic changes in the animal model of TS with highest degree of homology, the D1CT-7 transgenic mice, which exhibit tic-like manifestations. The results of these studies will set the stage for future large-scale NIH-funded translational studies aimed at the development of new therapeutic strategies for TS with limited side effects.


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