Identification of Factors that Promote Midbrain Dopaminergic Fate from Embryonic Stem Cells and Neural Stem Cells

Parkinson's disease is a progressive neurological disorder caused by the degeneration of midbrain dopaminergic neurons. While cell transplantation has shown promising clinical benefit in some patients, several difficulties remain to be addressed before this could be considered as a routine treatment. A particular problem is associated with the fact that we do not have sufficient knowledge of how to make the transplanted cells survive well and connect appropriately in the recipient brain. Therefore we are seeking novel regulators for the determination of midbrain dopaminergic fate, and for nigrostriatal axon growth. Using modern DNA chip technology, we have identified a number of candidate molecules. We propose to test these molecules for their ability to direct dopaminergic differentiation from embryronic stem cells, and/or to promote neuritogenesis of midbrain dopaminergic neurons. Knowledge obtained from these studies would have implications for the eventual application of stem cells in cell based therapies for Parkinson's disease. The development of a robust dopamine neuron differentiation protocol from ES cells would also aid the development of standardised culture systems to be used for Parkinson's related pharmaceutical drug screens.