Cell transplantation in Parkinson's disease: how can we make it work?
Previous open-label clinical trials have provided proof of principle that intrastriatal transplants of fetal dopaminergic neurons can induce substantial and long-lasting functional benefits in patients with Parkinson's disease. However, in two recent NIH-sponsored double-blind trials, functional improvements were only marginal and the primary endpoints were not met. Severe off-phase dyskinesias were observed in a significant proportion of the transplanted patients, raising doubts about the viability of the cell-transplantation approach. Here, we discuss the problems raised by the NIH-sponsored trials and point to several shortcomings that might explain the overall poor outcome, and we identify several crucial issues that remain to be resolved to develop cell replacement into an effective and safe therapy.
Winkler
Christian
C
Department of Neurology, Hannover Medical School, 30625 Hannover, Germany. winkler.christian@mh-hannover.de
Kirik
Deniz
D
Björklund
Anders
A
D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D004298:Dopamine