Cell Therapeutics in Parkinson’s Disease |
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Authors: | Olle Lindvall Anders Björklund |
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Institution: | 1.Laboratory of Neurogenesis and Cell Therapy, Wallenberg Neuroscience Center,University Hospital,Lund,Sweden;2.Neurobiology Unit, Wallenberg Neuroscience Center, BMC A11,Lund,Sweden;3.Lund Stem Cell Center,Lund,Sweden |
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Abstract: | 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. |
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