Further Studies on Autoimmune Mechanisms in Tourette Syndrome and Relates Neuropsychiatric Disorders

Grant Type
Clinical
Grant Year
2000-2001
Institution Location
NY
Institution Organization Name
Cornell University Medical Center
Investigators Name
Trifiletti, Rosario, MD, PhD

One of the most exciting developments in Tourette Syndrome (TS) research over the past decade has been the recognition that at least a subset of cases seems to be associated with an infectious trigger. In some instances, this trigger is thought to be Group A streptococcus, the bacterium that is responsible for common strep throat. Children who have sudden onset or marked exacerbation of either tics or obsessive-compulsive behaviors associated with streptococcal infection are said to have PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus). Our research team has begun to examine the immune system in patients with TS, OCD and PANDAS. We have found that there are changes in the immune system in these disorders which closely resemble those seen in Sydenham’s chorea (a type of movement disorder seen with rheumatic fever). These are conditions which have long been known to be triggered by streptococcal infections. Because patients with Sydenham’s chorea have been shown to have anti-brain antibodies in their blood which seem to be related to the development of movements, many have wondered whether patients with TS, OCD or PANDAS display such antibodies. After examining over 100 patients, we found two types of antibodies: one directed against brain protein ts83 and another against brain protein ts60. About 60% of patients with TS have serum antibodies to ts83, and 60% have antibodies to ts60. While only 15% of TS patients have antibodies to both proteins, 100% of TS patients have antibodies to either protein. However, we believe that no more than 10% of patients without TS, OCD or PANDAS display antibodies to one or another of these proteins. We also think that the presence of a serum antibody to ts83 or ts60 represents a significant risk factor for TS symptoms. This vulnerability can be determined by a blood test. Because these proteins could be important in the mechanism of disease, the goal of this study is to determine what ts83 and ts60 are. With TSA funding, we have been able to purify ts83 and have some information on its structure. Specifically, we believe that it may be a special brain form of a protein called calpain. Also, we hypothesize that ts60 is a closely related protein. If our further studies bear out these theories, we may have identified a key molecule in the brain that could be the target of the abnormal immune response in TS. Since calpain is an enzyme protein which can be turned off with specific drugs, this avenue of research might lead to entirely new drug treatments for TS. Rosario R. Trifiletti, M.D., Ph.D. The New York Hospital-Cornell University Medical Center, New York, NY Award: $40,000 Tourette Association of America Inc. – Research Grant Award 2000-2001