Cell therapy for Parkinson disease

Abstract

Advances in the field of stem cell research have raised hopes of creating novel cell replacement therapies for Parkinson disease (PD), although double-blinded clinical trials have met with controversial success in patients implanted with fetal midbrain tissue and autopsy results have shown that some of the grafted fetal neurons displayed pathological changes typical of PD. Dopaminergic neurons have been efficiently derived from stem cells using various methods, and beneficial effects after transplantation have been demonstrated in animal models of PD. Some obstacles remain to be overcome before stem cell therapy can be routinely and safely used to treat PD in humans. A widely used prodrug/suicide gene therapy would be applied to stem cells to reduce risk of tumor formation. Since grafts were transplanted ectopically into the striatum instead of the substantia nigra in most current protocols, surviving dopaminergic neurons would not have to be the same subtype as the nigral cells. If the main mechanism underlying any functional recovery achieved by cell therapies is restoration of dopaminergic neurotransmission, then viral vector-mediated gene delivery of dopamine-synthesizing enzymes represents a more straightforward approach. Future targets for cell therapy should include some types of Parkinsonism with degeneration of striatal neurons.