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Neural stem cell-derived neurons offer new cellular therapeutic alternatives for diseases of the central nervous system. Selective neural repair can be particularly valuable in progressive degenerative diseases with discrete cell loss, like Parkinson's disease. Some benefits were previously demonstrated following transplantation of fetal embryonic tissue. This approach, however, carries inherent risks of immunological reactions, infectious transmission, and intractable dyskinesias, in addition to serious ethical concerns.
Cortical and subcortical tissue samples were obtained during neurosurgical procedures. Neural stem cells were isolated and expanded in vitro for several months. Safety, differentiation and functional studies were performed during the expansion phases. Nine months after harvesting, autologous cell suspensions containing differentiated dopaminergic and GABAergic neurons were microinjected unilaterally in a patient with advanced Parkinson’s disease. 18F-dopa PET studies and neurological evaluations were performed serially (pre/post-operatively).
Over the next 36 months, the overall Unified Parkinson’s Disease Rating Scale (UPDRS) improved by 81% while “on” medication and 83% while “off” medication. At five-years post-operatively, clinical motor scores returned to baseline.
At three and twelve months post-operatively, 18F-dopa PET studies showed a 55.6% and 33.2% increase in dopamine uptake in the implanted left putamen.
Adult neural stem cells derived from a patient's cerebral tissue can become a source of differentiated neurons, useful for grafting in the treatment of Parkinson's disease. The combined GABAergic and dopaminergic cells produced a long lasting motor improvement. This approach has the potential to make neural stem cell therapy acceptable and available to a large number of patients.