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- CLINICA NEUROL, 43: 835－838, 2003
- Vol.43 No.11 contents
The 44th Annual Meeting of the Japanese Society of Neurology
Symposium 4-6: AAV vector-mediated gene transfer and its application to the nervous system
Keiya Ozawa, M.D., Ph. D.
Division of Hematology, Department of Medicine; Division of Cell Transplantation and Transfusion; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School
AAV vectors are considered to be promising gene-delivery vehicles for gene therapy, because they are derived from non-pathogenic virus, efficiently transduce non-dividing cells, and cause long-term gene expression. Appropriate AAV serotypes are utilized depending on the type of target cells; e.g., neurons are efficiently transduced with AAV2 and AAV5 vectors, and an AAV1 vector is most suitable for muscles. Among various neurological disorders, Parkinson's disease (PD) is one of the most appropriate candidates of gene therapy. PD is a progressive neurodegenerative disorder that predominantly affects dopaminergic neurons in the substantia nigra. There are two major approaches to gene therapy of PD; i.e., 1) intrastriatal expression of dopamine (DA) -synthesizing enzyme genes, and 2) neuroprotection using the glial cell line-derived neurotrophic factor (GDNF) gene to prevent the disease progression. As for the initial step of clinical application, AADC (aromatic L-amino acid decarboxylase; the enzyme converting L-DOPA to DA) gene transfer in combination with oral administration of L-DOPA would be appropriate, since DA production can be regulated by the dose of L-DOPA. Preclinical studies are being conducted in MPTP-parkinsonian monkeys. AAV vector-mediated gene therapy would be feasible as a novel treatment of PD in the near future.
(CLINICA NEUROL, 43: 835－838, 2003)
key words: gene therapy, AAV vector, Parkinson's disease, Dopamine-synthesizing enzyme gene, GDNF gene
(Received: 16-May-03)
