Abstract
The characteristic and selective degeneration of a unique population of cells—the nigrostriatal dopamine (DA) neurons—that occurs in Parkinson’s disease (PD) has made the condition an iconic target for cell replacement therapies. Indeed, transplantation of fetal ventral mesencephalic cells into the DA-deficient striatum was first trialled nearly 30 years ago, at a time when other treatments for the disease were less well developed. Over recent decades standard treatments for PD have advanced, and newer biological therapies are now emerging. In the 21st century, stem cell technology will have to compete alongside other sophisticated treatments, including deep brain stimulation and gene therapies. In this review we examine how stem cell–based transplantation therapies compare with these novel and emerging treatments in the management of this common condition. J. Comp. Neurol. 522:2802–2816, 2014.
Highlights
Treating Parkinson’s disease (PD) requires choices, for patients and families, for physicians, and for societies
With its selective dopaminergic cell degeneration, PD has been at the forefront of attempts to use novel cell replacement strategies to restore a normal dopamine (DA) supply to the striatum
This review examines where stem cells may fit, alongside other existent and proposed therapies, in the future management of this common disease (Fig. 1)
Summary
Whereas the door seemed to be closing on transplantation at the turn of the millennium, stereotactic neurosurgery, long used as a treatment for difficult movement disorders, was seeing a renaissance. As the therapeutic effect probably requires this transport, the group took the logical step of evaluating dual injections to the SN and striatum (Bartus et al, 2013; Bartus et al, 2011) This strategy has failed in blinded studies, analysis of subgroups showed significant improvements in UPDRS III OFF scores in those treated within 5 years of diagnosis (Ceregene, 2013). Better delivery methods are being explored in a trial just started in Bristol (UK), including “convection-enhanced delivery” (CED) (Taylor et al, 2013), delivery of the GF by gene therapy, rather than implanted catheter, seems likely to be the eventual technology To this end, a phase I study sponsored by the U.S National Institute of Neurological Disorders and Stroke (NINDS) has recently opened to recruitment, using AAV2-GDNF injected surgically via a CED system (ClinicalTrials.gov)
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