Cell replacement therapy in human neurodegenerative disorders

Clinical studies with intrastriatal transplants of embryonic mesencephalic tissue in patients with Parkinson's disease (PD) provide proof- of-principle for the cell replacement strategy in the diseased human brain. The grafted dopaminergic neurons can reinnervate the denervated striatum, restore regulated dopamine release and movement-related frontal cortical activation, and give rise to significant symptomatic relief. In the most successful cases, patients have been able to withdraw -DOPA treatment after transplantation and resume an independent life. However, it is unlikely that transplantation of human primary embryonic tissue can be developed into therapies for large numbers of patients. Stem cells could be useful as an unlimited source of specific neuron types, e.g. dopamine neurons. So far, neurons with at least some dopaminergic characteristics have been generated from stem cells. However, their survival after grafting in animal models has been poor and it is also unclear if they function as normal dopamine neurons. It is important to emphasize that the biological problems which have to be solved in order to develop stem cell-based therapies for neurodegenerative disorders like PD are complex and should not be underestimated. Progress should therefore be made with great care.