Cell therapy for Parkinson's disease - status and perspectives
2011
Idiopathic Parkinson’s disease (PD) is caused by progressive degeneration of melanin containing dopaminergic neurons in substantia nigra pars compacta in the upper brain stem. The loss of dopaminergic neurons results in a gradual decrease of dopaminergic input to the striatum leading to the cardinal symptoms rigidity, tremor, hypokinesia and occasionally postural instability. One of the prospects for a curative treatment for PD is to replace the lost dopaminergic neurons by intracerebral transplantation. Grafting of fetal midbrain dopaminergic neurons into the dopamine-depleted striatum has thus emerged as an experimental therapeutic approach for PD. Preclinical and clinical trials have demonstrated that such fetal dopaminergic neurons have the potential to markedly improve motor function in animal models and PD patients. Over the last decades, approximately 400 PD patients have been grafted, and graft survival in the dopamine-depleted striatum, with substantial motor improvements, has been reported particularly in younger patients. However, looking across all the studies, where several different protocols and donor ages have been used, the symptomatic relief is inconsistent and not yet of a magnitude that would justify treatment at a large scale. Ethical concerns related to the use of human fetal brain tissue, shortage of suitable donor tissue and a poor survival of grafted dopaminergic neurons has stimulated the search for other reliable sources of donor material and development of applicable gene technological techniques for improving graft survival, differentiation and functional integration. Expanded midbrain precursor cells, predifferentiated human embryonic stem cells or induced pluripotent stem cells as well as human neural stem cells and mesenchymal stem cells have been proposed as promising alternative sources of donor cells. In this chapter we will review current status and discuss crucial issues that remain to be resolved to develop cell replacement into an effective and safe therapy.
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