Transplantation of dopamine neurons in Parkinson's disease has resulted in significant improvements for some patients. However, large-scale clinical trials are impossible due to the technical and ethical issues surrounding the use of fetal tissues required for these programs. Neural stem cells can be derived from human fetal brain tissue and expanded in culture for long periods of time and represent a valuable alternative. However, they do not give rise to large numbers of dopamine neurons. This grant will use two approaches to generate more dopamine neurons from human neural stem cells. The first will identify small numbers of developing dopamine neurons and try to enrich and expand them. The second will use gene transfer methods to "force" the cells to turn into dopamine neurons. These will then be transplanted into animal models of Parkinson's disease. Finally, we will establish a tissue bank that will be able to distribute well-characterized human neural stem cells to other researchers.