Worldwide attention is presently focused on the potential use of exogenous progenitor cells as a source of cells for transplantation therapy in neurodegenerative diseases such as Huntington's and Parkinson's disease. Because controversy has surrounded the use of human fetal and embryonic tissue for the purposes of experimentation and transplantation, new sources of cells for transplantation have been sought. Less controversial, and probably more notable, is the recent demonstration of the presence of endogenous progenitor cells in the adult human brain in both the hippocampus and the subependymal layer overlying the caudate nucleus. 1,2 These observations indicate that, contrary to the well rehearsed dogma, the adult human brain contains progenitor cells that are capable of producing new neurons. This raises the possibility that endogenous neural progenitor cells may provide an alternative strategy for cell replacement therapy through the enhancement of endogenous neural replacement mechanisms to produce new neurons that replace the cells that die in neurodegenerative diseases.We have recently demonstrated that in Huntington's disease (a progressive autosomal dominant neurodegenerative disorder that principally affects the striatum) there are significantly more dividing cells in the subependymal layer (the neurogenic layer that overlies the striatum) compared with controls. 2 In this study we have shown that about 5% of the cells that have recently divided become neurons and others become glial cells. In this case, the trigger for the increased cell production in the Huntington's disease brain appears to be the death of neurons in the striatum because as cell death advances in Huntington's disease more dividing cells are present in the subependymal layer of the diseased brain. However, in Huntington's disease it would appear that the increase in cell proliferation and neurogenesis is too little too late. If the proliferation, migration and differentiation of endogenous progenitor cells could be pharmacologically enhanced then progenitor cells may more effectively replace the specific cells that die in neurodegenerative diseases.Neural progenitor cells have been shown to respond to a variety of mitogenic growth/trophic factors and cytokines in vivo such as epidermal growth factor (EGF), fibroblast growth factor (FGF-2), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), erythropoietin (EPO) and others by facilitating the proliferation, migration and differentiation of progenitor cells in the adult central nervous system. [3][4][5][6][7][8][9][10][11][12][13][14] In one such in vivo study the growth factor EGF was infused into the lateral ventricle of adult mice; the results demonstrated a dramatic increase in the number of proliferating cells in the subependymal layer of the lateral ventrical. 9 Immunohistochemical analysis revealed that more than 95% of the cells present in the subependymal layer were immunopositive for the EGF receptor and were also nestin...