| Popis: |
Publisher Summary Because of certain limitations of current therapy for Parkinson's disease (PD) new therapeutic approaches to PD are must needed. Direct administration of therapeutic agents into the central nervous system (CNS) eliminates the need to bypass the blood brain barrier (BBB), thereby reducing systemic side effects. However, cellular implants can overcome the need for persistent and local physical delivery of therapeutic agents into the CNS. Several alternative approaches utilizing genetic engineering have been proposed by many investigators. Primary or immortalized cells have been engineered to produce a specific protein in culture, and the cells are then implanted into the host CNS either by direct cell transplantation or by encapsulating cells into semipermeable membranes. Other approaches consist of in vivo gene transfer based on direct introduction of genetic material into the CNS, using viral or synthetic vectors. Several vehicles have been used for in vivo transfer of cDNA, including herpes simplex viral vectors, adenoviral vectors, direct plasmid DNA transfer, and, most recently, retroviral vectors Ex vivo methods using primary fibroblasts transduced with retroviral vectors and the in vivo method utilizing adeno-associated virus (AAV) are also described in this chapter as possible means of chronic delivery of therapeutic agents into CNS. However, further technological advances are required to optimize gene delivery, regulation of gene expression, and testing in appropriate functional models before gene therapy can be used extensively. |
