Novel D3 Receptor Compounds for the Treatment of Tourette Syndrome (TS): a combined In Vivo and In Vitro Approach

Grant Type
Basic
Grant Year
2009-2010
Institution Location
CA
Institution Organization Name
University of California
Investigators Name
Weber, Martin, PhD

Current medications for Tourette Syndrome (TS) successfully treat some symptoms of TS, but their efficacy is limited because they often cause significant side effects and/or may not treat all symptoms. Thus, there is a clear need for new, more effective medications. Our collaborators, Drs. Mach and Luedtke, have made available to us for testing, a potentially novel class of medications to assess for the treatment of TS. These compounds may have the ability to treat TS with fewer side effects because they predominantly target the dopamine D3 receptor subtype, while other dopamine receptors that have been linked to major side effects in some current medications, remain largely unaffected. Our project involves three research avenues: First, to characterize these novel compounds, we have established a screening procedure in rats that enables us to detect drug effects on the dopamine D3 receptor. This procedure is based on prepulse inhibition of startle, a behavioral measure in which individuals with TS differ from those who do not have TS. Using our novel assay in rats, we successfully identified a promising drug with D3 activity, which our collaborators will now modify to increase its D3 receptor selectivity. Our second line of research elucidates the intracellular (biochemical) pathways linked to D3 receptor activation/blockade. Our third line of research aims to expand our repertoire of methods for screening potential TS medications, using a measure called visuospatial priming (VSP). Individuals with TS exhibit deficits in VSP, and these deficits can be used to predict which individuals will, or will not, respond to specific TS treatments. In summary, we are screening new candidate TS treatments, understanding how they act within the brain to change brain cells, and developing new and potentially more sensitive ways to detect them. Martin Weber, Ph.D., Jared Young, Ph.D. University of California at San Diego School of Medicine La Jolla, CA Award: $40,000 (Fellowship, 2nd Year) Commentary: There continues to be a great need for effective and safe medicines to control tics and other symptoms in individuals with Tourette Syndrome (TS). One limitation in developing novel TS medications has been the lack of animal models that predict how well new drugs will work in humans. Drs. Weber and Young are developing a new animal model for TS which, if successful, may predict treatment response in patients. This model will be tested using current medications for TS and will then be used to test a new compound that has been made available to the investigators. If successful, this study could lead to the identification of novel medications with fewer side effects that could one day become available to people with TS. Tourette Association of America Inc. – Research Grant Award 2009-2010