EMBRYONIC MOUSE STEM CELLS REPAIR BRAIN TOXICITY CAUSED BY ANTIPSYCHOTIC DRUGS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Kovoor is presently an assistant professor at the University of Rhode Island. Antipsychotic drugs have revolutionized the treatment of schizophrenia and other related mental disorders. However, a serious toxicity of chronic treatment with many antipsychotic drugs is the development of tardive dyskinesia (TD), an irreversible and debilitating movement disorder of unknown pathophysiology (Rascol and Fabre, 2001; Llorca et al., 2002; Casey, 2004; Margolese et al., 2005). L-DOPA-induced dyskinesia (LID) is a similar unexplained and debilitating toxicity of the pharmacotherapy of Parkinson's disease (Brotchie et al., 2005). The funded pilot grant proposal was designed to test the hypothesis that embryonic mouse stem cells genetically modified to express RGS9-2 and implanted into the striatum can treat TD and LID. The following two specific aims were proposed SPECIFIC AIM 1: We will test if mouse embryonic stem (ES) cells can stably express RGS9 2 and that expression is not silenced upon neuronal differentiation of the ES cells. SPECIFIC AIM 2: We will implant ES cell lines stably transfected with the RGS9 2 construct from Specific Aim 1 into dyskinetic RGS9 knockout mice and quantify the level of abnormal involuntary movements pre and post-implantation.