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May 23, 2006; 66 (10 suppl 4) Articles

Gene transfer of trophic factors and stem cell grafting as treatments for Parkinson’s disease

Biplob Dass, C. Warren Olanow, Jeffrey H. Kordower
First published May 22, 2006, DOI: https://doi.org/10.1212/WNL.66.10_suppl_4.S89
Biplob Dass
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C. Warren Olanow
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Jeffrey H. Kordower
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Citation
Gene transfer of trophic factors and stem cell grafting as treatments for Parkinson’s disease
Biplob Dass, C. Warren Olanow, Jeffrey H. Kordower
Neurology May 2006, 66 (10 suppl 4) S89-S103; DOI: 10.1212/WNL.66.10_suppl_4.S89

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Abstract

Current therapies for Parkinson’s disease (PD) are limited in their ability to control PD symptomatology, are associated with motor and psychiatric side effects, and do not prevent disease progression. Considerable scientific and media interest has focused on the potential value of gene and stem cell therapies to overcome these problems and to enhance the quality of life for PD patients. Gene therapies utilize a viral vector to deliver a protein of interest to specific brain region. Clinical trials of gene therapy are currently underway using adeno-associated virus to deliver AADC to the striatum, the trophic factor nurturin to the striatum, and GAD to the STN. To date, no serious adverse effects have been noted, but only a small number of patients have been studied. Stem cells are pluripotential cells that offer the potential of generating unlimited numbers of optimized dopamine cells for transplantation. Stem cells can be grown and expanded in tissue culture and then induced to differentiate into dopamine neuronal phenotypes. Transplantation of these cells into the striatum is associated with behavioral improvement in 6-OHDA rodents and MPTP monkeys. Still, only small numbers of transplanted dopaminergic cells survive, and benefits are modest. Clinical trials in PD have not yet been performed. There is considerable enthusiasm for the potential of these procedures, but there remains much to learn in the laboratory and neither has been established to be effective as a treatment for PD. Long term safety and efficacy trials have not been performed in PD patients and the potential of unanticipated side effects must be addressed. Further, neither treatment is expected to improve the non-dopaminergic features of PD.

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