Developing dopaminergic cell therapy for Parkinson's disease--give up or move forward?

Despite 3 decades of basic and clinical studies, there is still no dopaminergic cell therapy for Parkinson's disease. Several arguments have been put forward why this approach, so far tested with transplantation of human fetal mesencephalic dopamine-rich tissue, will never be of clinical use and should be abandoned: (1) Lack of efficacy in 2 sham surgery-controlled trials; (2) occurrence of troublesome off-medication dyskinesias in a subgroup of grafted patients; (3) disease process destroys grafted neurons; and (4) non-motor symptoms will not be influenced by intrastriatal dopaminergic grafts. Here, the author argues that, based on recent scientific advancements, the development of a dopaminergic cell therapy for Parkinson's disease should continue. Factors influencing the outcome after transplantation have now been identified, and dopaminergic neurons can be generated in large numbers from stem cells. Mechanisms of graft-induced dyskinesias are much better understood, and patients with well functioning grafts can exhibit long-term motor recovery of therapeutic value even in the presence of non-motor symptoms.