- Gene Therapy for Parkinson’s: Disease from Bench to Bedside

Gene therapy involves the introduction of a novel genetic sequence to a specic population of cells, either ex vivo or in vivo, for the purpose of de novo synthesis of proteins or various peptides, or to reduce gene expression of endogenous (toxic) proteins. An engineered vector containing the desired genetic sequence facilitates the transduction of the target cells. Gene therapy for Parkinson’s disease (PD) can be used to continuously produce large molecules like dopamine (DA) or its precursors by overexpressing enzymes involved in DA synthesis, as well as various trophic factors inside the

blood-brain barrier (BBB), or other molecules aimed at intersecting the disease processes in the disease, without the use of indwelling mechanical devices such as pumps or reservoirs. A neurosurgical procedure is still required to deliver the gene therapy vector to a localized delivery area. Therefore, the treatment of PD continues to be a major focus for neurological gene therapists because it will be sufcient to deliver a transgene or reduce expression of a gene in a particular anatomical region to the exclusion of global delivery. This chapter will review the current gene therapy strategies under investigation for the treatment of PD and will discuss gene therapy treatments for PD that have reached clinical trial status.