Embryonic stem (ES) cells are non-transformed primitive cells derived from early embryos and are capable of essentially unlimited proliferation in an undifferentiated state yet retain the potential to give rise to all cell and tissue types of the body. Thus ES cells provide an almost limitless source for deriving specialized cells for cell therapy. Both human and nonhuman primate ES cell lines have been established by James Thomson of the Wisconsin Regional Primate Research Center and they behave similarly in vitro and in vivo. This proposal will explore the feasibility of using rhesus monkey ES cells (which are available only from the Wisconsin Regional Primate Research Center) as a source to produce dopamine neurons, the major cell type lost in human Parkinson?s disease. First, the ES cells will be directed to neural precursors in a "neural promoting" condition. Second, the ES cell-derived neural precursors will be coaxed to become specialized dopamine neurons based on the developmental requirement of midbrain dopamine neurons. Third, the ES cell-derived dopamine neurons will be examined for their therapeutic potential in restoring motor dysfunction in a rat model of Parkinson?s disease. If successful, this exploratory/developmental grant (R21) will be expanded to a five-year proposal to transplant the monkey ES cell-derived dopamine neurons to a monkey model of Parkinson?s disease in the future. Information gained from these studies will be crucial in ultimately utilizing human ES cells to treat neurological illnesses including Parkinson?s disease.