Neuronal cell replacement in Parkinson's disease

Abstract

Transplantation of foetal dopamine neurons into the striatum of Parkinson's disease patients can provide restoration of the dopamine system and alleviate motor deficits. However, cellular replacement is associated with several problems. As with pharmacological treatments, cell therapy can lead to disabling abnormal involuntary movements (dyskinesias). The exclusion of serotonin and GABA neurons, and enrichment of substantia nigra (A9) dopamine neurons, may circumvent this problem. Furthermore, although grafted foetal dopamine neurons can survive in Parkinson's patients for more than a decade, the occurrence of Lewy bodies within such transplanted cells and reduced dopamine transporter and tyrosine hydroxylase expression levels indicate that grafted cells are associated with pathology. It will be important to understand if such abnormalities are host- or graft induced and to develop methods to ensure survival of functional dopamine neurons. Careful preparation of cellular suspensions to minimize graft-induced inflammatory responses might influence the longevity of transplanted cells. Finally, a number of practical and ethical issues are associated with the use of foetal tissue sources. Thus, future cell therapy is aiming towards the use of embryonic stem cell or induced pluripotent stem cell derived dopamine neurons.