In previous work, we have successfully generated functional dopamine neurons from both fetal CNS- and embryonic stem cells in animals. More recently (in collaboration with Rockefeller University) we have achieved the derivation of dopaminergic neurons from adult somatic cells such as animal cells or cumulus cells via nuclear transfer. In this proposal, we capitalize on these exciting preliminary findings and plan to optimize several aspects of this burgeoning technology, with a view towards restorative therapy in Parkinson's disease. Our goals are to (1) achieve efficient and reproducible in vitro generation of midbrain dopamine neurons from animal embryonic stem cells established via nuclear transfer from adult somatic cells (ntES cells), and (2) to purification of the resultant ntES-derived CNS cell population from cells of non-CNS origin via promoter driven selection. We will then carry out pilot studies addressing the in vivo potential of purified populations of ntES derived dopamine neurons in an animal model of Parkinson's disease. In comprehensively combining ES and cloning technologies, we will contribute toward a renewable source of isogenic cells for transplantation, originating from adult somatic cells.