Funded Studies
One of the promising potential treatments for halting the progress of Parkinson's disease and restoring lost function is cell replacement using dopamine producing neurons derived from human embryonic stem cells. Progress in the development of a cell therapy product is currently being slowed by the poor survival and function of stem cell derived dopaminergic neurons after transplantation. In the present project we plan to carry out a focused and methodological research program that will lead to the identification and selection of the progenitors of dopaminergic neurons that will have the best chance of surviving and flourishing after transplantation. The ultimate goal is to achieve complete behavioral recovery in rodent models of Parkinson's disease. We will initially characterize the timing for the expression of key landmark factors in cells as they differentiate from human embryonic stem cells into dopaminergic neurons in the laboratory. In parallel we will harvest cells at sequential time points during their differentiation, transplant them into Parkinsonian rats and monitor the number of dopaminergic neurons per cell graft and improvement in behavior. This will identify the time window and stage of differentiation required for optimal transplantation results. We will also develop human embryonic stem cells expressing reporter molecules and use them as tools for optimizing the cell production and transplantation results in animal models. Finally, we will also evaluate whether transplantation results can be improved using substances known to increase cell survival.
Final Outcome
Dr. Wiser found that hES cells undergoing differentiation into dopamine neurons show several patterns of gene expression markers. One particular set of markers appears to give the greatest munber of grafted dopamine neurons when transplanted into the brains of pre-clinical models. However, it was not possible to determine as part of this project whether these grafts were viable and could lead to functional improvements. Future work is likely to improve our understanding in this area.