Journal
NEUROTHERAPEUTICS
Volume 8, Issue 4, Pages 539-548Publisher
SPRINGER
DOI: 10.1007/s13311-011-0069-6
Keywords
Neural transplantation; Dopamine neurons; Parkinson's disease; Stem cells; Dyskinesias
Funding
- Swedish Research Council
- EU [22943]
- Swedish Government Initiative for Strategic Research Areas (StemTherapy and MultiPark)
- Michael J. Fox Foundation, New York, USA
Ask authors/readers for more resources
The main pathology underlying motor symptoms in Parkinson's disease (PD) is a rather selective degeneration of nigrostriatal dopamine (DA) neurons. Intrastriatal transplantation of immature DA neurons, which replace those neurons that have died, leads to functional restoration in animal models of PD. Here we describe how far the clinical translation of the DA neuron replacement strategy has advanced. We briefly summarize the lessons learned from the early clinical trials with grafts of human fetal mesencephalic tissue, and discuss recent findings suggesting susceptibility of these grafts to the disease process long-term after implantation. Mechanisms underlying graft-induced dyskinesias, which constitute the only significant adverse event observed after neural transplantation, and how they should be prevented and treated are described. We summarize the attempts to generate DA neurons from stem cells of various sources and patient-specific DA neurons from fully differentiated somatic cells, with particular emphasis on the requirements of these cells to be useful in the clinical setting. The rationale for the new clinical trial with transplantation of fetal mesencephalic tissue is described. Finally, we discuss the scientific and clinical advancements that will be necessary to develop a competitive cell therapy for PD patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available