A number of recent studies have suggested that some specific cases of Tourette Syndrome (TS) and related disorders, such as obsessive-compulsive disorder (OCD) may be triggered by infections. Part of the suggestive evidence includes the clinical and biological similarity among TS, OCD and another movement disorder known as Sydenham’s chorea (SC). SC is triggered by streptococcal infection, and is one part of a medical disorder known as rheumatic fever. Antibodies to brain molecules can be found in the blood of patients with SC, and this led us to look for similar antibodies in patients with TS and OCD. We have found that about 80% of patients with TS and OCD seem to have antibodies to a specific brain protein which we have called ts83. We have isolated ts83, and have found good evidence that it is a special form of a molecule called calpain, a protein-metabolizing enzyme found in both the brain and elsewhere in the body. Over-activation of a brain form of calpain could lead to the “neurochemical imbalance” that appear to underlie both TS and OCD. If our studies can be confirmed and extended, they could represent a completely new avenue of research into the cause of TS and OCD which might lead to new types of treatment. In fact, one calpain inhibitor, valproate, has already been found to be successful in drug-resistant OCD. We sincerely hope that this research will lead to both a better understanding of these disorders and ultimately to more effective treatments. Rosario R. Trifiletti, M.D., Ph.D. Cornell University Medical Center/New York Hospital, New York, NY Award $39,800 Tourette Association of America Inc. – Research Grant Award 1999-2000