Project Summary

KavithaYaddanapudi, Ph.D. (Young Investigator 2005) of Columbia University, plans to study an animal model of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, or PANDAS. Children with PANDAS develop obsessive-compulsive or tic disorder during streptococcal infections. They respond to immunomodulatory treatment with plasma exchange and intravenous immunoglobulin and the frequency of attacks is reduced with antibiotic therapy. These features suggest that antibodies induced by streptococcal infection cause disease. To investigate the role of antibodies in PANDAS, Dr. Yaddanapudi created an animal model of PANDAS. Mice immunized with streptococci develop abnormal behaviors and immune deposits in brain. Using molecular techniques, Dr. Yaddanapudi determined that these deposits contain antibodies directed against Hsc70, a protein implicated in neuropsychiatric and neurodegenerative disorders. Sera from children with PANDAS also contain antibodies to the Hsc70 protein. This project will: 1) determine in a PANDAS mouse model whether anti-Hsc70 antibodies alone can cause disease; 2) assess the prevalence and titer of antibodies to Hsc70 in children with PANDAS; 3) identify the bacterial proteins that cross-react with mouse and human anti-Hsc70 antibodies; 4) examine the mechanisms by which bacterial proteins may lead to production of autoantibodies against Hsc70. These studies will provide important insights into the basis of autoimmune brain disorders, and may lead to new strategies to identify and treat children at risk for PANDAS.

Program Area: MULTIPLE FOCUS AREAS\Tourette's Syndrome/OCD

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