Approach to ex vivo gene therapy in the treatment of Parkinson's disease

Approaches to ex vivo gene therapy hold great promise for the treatment of central nervous system disorders where there is currently no care or enough treatment for suffering patients. In this review we have focused on the application of ex vivo gene therapy techniques in Parkinson's disease models, however, the issues and approaches are applicable to other neurodegenerative disorders. In utilizing the ex vivo strategy two considerations are critical for delivery of therapeutic levels of transgene product to the target organ: (i) the vector system and (ii) the cell type for grafting. We describe different vector systems that are currently available and review the various cell types that have been genetically modified and grafting into the striatum of animal models with experimental Parkinson's disease. The strategies for application of gene therapy techniques to the treatment for Parkinson's disease have expanded beyond the classical dopamine replacement toward the use of neurotrophic factors in enhancing cell function or preventing cell death. In addition, we explore the utility of autologus primary skin fibroblasts as alternative cell type for ex vivo gene therapy in the animal model of Parkinson's disease. These results have general implications for the application of ex vivo gene therapy to human neurological diseases and specific implications for Parkinson's disease.