Cell therapy for Parkinson's disease: problems and prospects.
Cell replacement therapy in Parkinson's disease (PD) has so far been based on the use of primary dopaminergic (DA) neuroblasts obtained from the brain of aborted human fetuses. Clinical trials show that intrastriatal DA neuron transplants can give substantial symptomatic relief in advanced PD patients. Two recent NIH-sponsored placebo-controlled trials, however, have given disappointing results and highlighted a number of critical issues that need to be resolved in order to turn cell transplantation into an acceptable clinical therapy. First, graft survival and clinical outcome has so far been too variable, suggesting that DA neuron grafts may not be equally effective in all PD patients. Secondly, it has become clear that immune mechanisms leading to slowly developing inflammatory responses may compromise long-term graft survival and function. Third, the problems associated with the use of tissue from aborted fetuses make it necessary to develop alternative sources of cells for transplantation. Recent progress in the generation of DA neuroblasts from neural progenitors and embryonic stem cells suggest that these kinds of cell may offer more accessible, defined and standardized sources of cells for clinical transplantation in PD.
Björklund
Anders
A
Wallenberg Neuroscience Center, Division of Neurobiology, Lund University, BMC A11, S 22184 Lund, Sweden.
D002454:Cell Differentiation / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D010300:Parkinson Disease / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation
D004298:Dopamine