Cell replacement therapy for Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the degeneration of dopaminergic neurons projecting from the substantia nigra to the striatum is a key pathological feature of the disease. Although pharmacological dopamine replacement is generally very effective in early disease, it is only a symptomatic therapy and can have significant side effects with long term use. One of the key strategies in a more restorative approach to PD therapy involves replacement of this degenerating nigro-striatal dopaminergic network with cells and several possible cell sources are being explored. While much experience and some success have been gained with fetal ventral mesencephalic (FVM) tissue transplants, the rapidly advancing stem cell field is providing attractive alternative options which circumvent many of the ethical and practical problems inherent in trials with FVM tissue. Of these embryonic stem cells and induced pluripotent stem cells seem the most promising. However further development and optimisation of the safety and efficacy of the techniques involved in generating and manipulating these, as well as other, cell sources will be essential before any further clinical trials are carried out.

Basic science in Parkinson’s disease: its impact on clinical practice

“…But a lot of pre-clinical research in cell culture and animal models still needs to be done before the transplantation of stem cells can be regarded as a feasible therapeutic strategy. Principally, stem cells might serve as a source for allografts [embryonic stem cells (ESCs), fetal neural precursor cells] or autografts [endogenous adult neural precursor cells, carotid body stem cells, mesenchymal stem cells, induced pluripotent stem (iPS) cells] [70]. Human ESCs extracted from the blastocyst were best differentiated into dopaminergic neurons in vitro using a combination of feeder cells and growth factors [55,57,61], but propagation of selected neural precursor cells from cultured aggregates of ESCs proved to be even more successful [15].…”

Induction and Transplantation of Neural Stem Cells from Human Pluripotent Stem Cells in Experimental Models (Rat) of Parkinson's disease

“…Its main pathology is the degeneration of dopaminergic (DA) neurons in the A9 region of the substantia nigra (Damier et al 1999). The treatment of PD is generally dopamine replacement therapy, but long-term use can cause side effects (Wijeyekoon and Barker 2009). Cell replacement therapy in PD has been studied as a potential alternative treatment to sustain DA neural functions.…”

Treatment strategies for Parkinson’s disease

“…Transplantation of fetal dopaminergic cells can provide functional and biochemical improvement in animal models of PD [18] . off-medication dyskinesia [19] .…”