Dopamine on Demand: a Possible Step Toward Stem Cell Therapy for Parkinson's Disease
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Parkinson?s Disease (PD) is a degenerative brain disorder in which dopamine-producing cells in the substantia nigra are lost. Dopamine is a neurotransmitter that is essential for smooth motor control and the initiation of voluntary movement. The loss of these dopamine producing cells causes the classical symptoms of PD. Currently treatment involves pharmacotherapy with L-dopa, which is converted to dopamine in the remaining cells. Unfortunately, since many of the cells capable of converting L-dopa to dopamine have died, the therapeutic window begins to close after about five years. Also, the treatment itself has been shown to cause involuntary movements, or dyskinesias. A different approach to treatment is cell therapy, which seeks to replace the cells that are lost due to the disease. We have genetically engineered a stem cell line to express dopa decarboxylase and tyrosine hydroxylase, enabling these cells to produce dopa and convert dopa to dopamine. We have been able to characterize these cells biochemically using HPLC. By engineering stem cells in this way we can control the amount of dopamine produced by regulating the amount of dopa. One major concern in using stem cells is that undifferentiated mitotic cells will cause tumors upon transplantation. Our cells have also been engineered to over express OCT ? causing them to spontaneously differentiate into neurons upon removal of trophic factors, significantly decreasing the concern of undifferentiated cells forming tumors. Our goal is to identify cells that produces dopamine on demand, transplant into an animal model of PD, and treat with L-Dopa.