Animal models are among the most important tools for understanding complex disorders. They greatly facilitate rapid drug screening, understanding brain mechanisms, and studying the effects of abnormal genes. A common misconception is that animal models are supposed to “look like”the human condition they are modeling. On the contrary, important animal models of TS may bear little resemblance to the condition itself, but they may involve a protein, receptor, gene or brain circuit that is affected in causing TS. In other words, they may be very informative about the biology of TS.In fact, at virtually every major TS scientific conference discussion inevitably turns to the issue of the development of an animal model for this disorder. Faced with the importance of this scientific mission, the TSA advertised a special RFA (Request for Applications) to encourage the best proposals with the specific goal of developing animal models of relevance to this disorder. A group of eight scientists from the TSA Scientific Advisory Board (SAB) worked hard to develop specific criteria for applicants to consider when proposing to develop such a model. More than a dozen proposals were received and carefully reviewed by a committee of the SAB. The TSA is very pleased to be able to support three of these investigations at this time. Dr. James Bibb (University of Texas, Southwestern) will trigger an immune reaction in mice by injecting them with sera from individuals with TS. A TSA funded investigator, Dr. Bibb has reported that he can identify a target of this immune reaction that might also be a target in human autoimmune conditions that are implicated in some forms of TS. If this model is successful, it could have broad applications—from studying autoimmune reactions related to streptococcal infections, to developing treatments or vaccines for immune-mediated movement disorders, to understanding the brain mechanisms involved in the more common forms of TS. In two other projects, scientists from Yale University—led by Dr. Jane Taylor and from Cardiff University (UK)—led by Dr. Simon Killcross—will use animal models to study the mechanisms within the frontal cortex and basal ganglia that are responsible for the persistence of abnormal motor patterns or “habits.” Funded by the NIH, a TSA Behavioral Sciences Consortium is already studying behavioral therapies for TS based on the ability of the cortex and basal ganglia to “unlearn” motor patterns that fuel tics. The models by Taylor and Killcross will be used to examine the cellular processes that transpire in specific brain regions –the cortex and the basal ganglia—during the formation of these abnormal repetitive motor patterns. These models will also help determine whether specific medications can be used to help “undo” those patterns. As TS genes are identified (see summary of Dr.State’s report), the imperative to have such models in place as part of the TSA scientific “armory” will be critical over the next few years.Once these genes are found, a very important next scientific step is to develop rodents with mutations of those genes in order to study their biological effects in models of relevance to TS. By proactively seeking and supporting the development of these three models, the TSA will be positioned to move quickly into the next phase of “post-gene”investigations, and along the way, we will gain important new insights into the immune and neural mechanisms related to TS. — Neal R. Swerdlow, Chair, TSA Scientific Advisory Board James Bibb, Ph.D. University of Texas, Southwestern Medical Center, Dallas, Texas Award: $74,500 Jane Taylor, Ph.D. Yale University School of Medicine, New Haven, Connecticut Award: $60,825 Simon Killcross, Ph.D. Cardiff University, Cardiff, United Kingdom Award: $74,387 Tourette Association of America Inc. – Research Grant Award 2005-2006