Identification of Proteins Involved in Tourette Syndrome-Year 2

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Texas
Investigators Name
Bibb, James, PhD

Neuropsychiatric disorders are a major frontier of neuroscience. While therapeutic treatments exist for a number of disorders, their effectiveness varies and many drugs can cause nonspecific side effects. Bridging the gap between basic research (in the laboratory) and clinical (patient) approaches is essential for advancement toward better treatments, preventions, and cures for these disorders. A major impasse in studying the causes of complex maladies such as Tourette Syndrome (TS) is identifying the seminal molecular or biochemical aberration from which all subsequent dysfunctions result. Finding biological markers for a complex behavioral or neuropsychiatric disorder is often tedious and difficult. Children in underdeveloped countries often develop a movement disorder, Sydenham’s chorea, as a result of contracting severe streptococcal infections and rheumatic fever. Interestingly, a substantial number of these patients also develop TS. Indeed, the likely source of these complications is an autoimmune reaction where, in response to the severe bacterial infection, the patient’s own immune system produces antibodies that may cross react with, or destroy, neuronal circuitry in the brain that is used for motor learning. As a result, tics, or undesired motor responses, may escape unrepressed. Based on this information, we hypothesized that the sera from patients with obsessive compulsive disorder (OCD), Sydenham’s, and possibly, rheumatic fever could contain antibodies that are able to specifically detect and target proteins in the brain that are critical to the reward/motor circuitry. We conducted preliminary studies and found that indeed, we could detect, isolate and identify proteins that were specifically recognized by Sydenham’s patients’ sera. As a result of this work we were awarded a grant from the Tourette Syndrome Association to conduct a more thorough biochemical search. For these studies, sera were provided from an extremely valuable cohort of TS and OCD patients assembled by Drs. James Leckman and Paul Lombroso at Yale University. These sera enabled us to purify more specific proteins. So far we have identified at least one protein that may be a potential target of autoimmunity in TS. We are continuing these studies and have initiated new experiments with other collaborators including Harry Hill at the University of Utah and Kevin McIver here at UT Southwestern. Together with our colleagues, we hope to move toward an animal model of TS and contribute to the development of new treatments. For this work, we have received a continuation of funding from TSA for a second year. We are grateful for this support, without which we could not conduct this basic-clinical bridging approach to our research. James A. Bibb, Ph.D. University of Texas Southwestern Medical Center, Dallas, TX Award: $66,850 (Year 2 Award) Tourette Association of America Inc. – Research Grant Award 2004-2005