The future of cell-based transplantation therapies for neurodegenerative disorders.

Abstract

Parkinson's disease is a common neurodegenerative disease with a lifetime incidence of 2.5% and a prevalence of at least 2% in individuals over 70 years old. Patients can be effectively treated with drugs that target the dopaminergic nigro-striatal pathway, but over time the efficacy of these medications is limited by the development of profound motor fluctuations and dyskinesias. This has prompted the search for alternative treatments, including the use of cell replacement therapies. Over the last decade, human fetal nigral transplants have demonstrated that dopaminergic neurons can survive and provide clinical benefit for patients with Parkinson's disease. However, there are clearly ethical concerns and a limit to the supply of this tissue as well as more recently anxieties over side effects. As a result, alternative sources of tissue have been investigated, and one such source are stem cells, which provide an attractive renewable tissue supply. In this review, we will discuss the current state-of-the-art and the characteristics of Parkinson's disease that increase its attraction as a target of stem cell therapy against results of current clinical trials using fetal neural grafts. Then we will discuss the various types and sources of stem cells, and some early transplantation results in animal models of Parkinson's disease. Finally we will discuss the prospect of using stem cells to deliver drugs and neurotrophic factors involved in neuroprotective and neuroreparative strategies in Parkinson's disease and other neurodegenerative conditions.