Characterizing the neuroprotective properties of neural precursors cells for the treatment of Parkinson's Disease

Neurodegenerative diseases such as Parkinson's disease (PD) are progressive neurological disorders that afflict thousands of Canadians each year. At present there are no known cures. Possible treatments include: 1) pharmacological intervention to decrease symptoms and reduce neuronal cell death and 2)transplantation of new cells to replace those that died due to the disease. Support for the latter strategy comes from studies indicating that locomotor skills are improved in animal models of PD when neural stem cells are transplanted into the diseased brain. The mechanisms underlying the improvement in behavour are not known. Recent recent work in our laboratories indicates that neural stem cells secrete at least one potent factor, known as sonic hedgehog (Shh), that protects neurons from dying in culture. At present, we do not know whether Shh is secreted by stem cells after they are transplanted into a diseased brain or whether this secretion accounts for the improvement in locomoter function observed in the transplanted animals. The aim of this proposal is to first develop genetically engineered neural stem cells that are incapable of producing sonic hedgehog. Second, once generated, their neuroprotective properties will be tested in tissue culture and after being transplanted in animal models of PD. Finally, it will be determined whether Shh is secreted by endogenous neual stem cells in the adult brain and, if so, whether this secretion is required for normal brain development and function. The outcome of this research will improve the health of millions of Canadians suffering from degenerative diseases because it will dictate how neural stem cell transplantation therapy in conducted in the future and it will provide some much needed insight into the function of endogenous stem cells in the adult and aging population.