Previous work has identified a stromal cell-derived inducing activity (SDIA) in a stromal cell line (PA6 cells) that can induce mouse and primate ES cells to differentiate into mid/hindbrain neurons, dopaminergic (DA) neurons in particular. In our previous study, these SDIA-treated pre-clinical model ES cells have been transplanted into the brains of MPTP-treated pre-clinical models of Parkinson's disease. Behavioral studies and functional imaging by PET for three months following the graft demonstrated that the transplanted cells functioned as DA neurons, attenuating the MPTP-induced neurological symptoms. These results suggest that transplantation of ES cells as a clinical therapy for Parkinson's disease is approaching the point of technical feasibility. We will be able to use human ES cell lines established by one of our collaborators in Japan. Using our experimental methods with modifications, we will determine whether the human ES cells can differentiate and function as DA neurons in our model of Parkinson's disease. The goal is to induce authentic DA neurons from the human ES cells, and to prove the effectiveness and safety of grafting them into the brains of MPTP-treated pre-clinical models.