title: Recombinant adeno-associated viral vectors bring gene therapy for Parkinson's disease closer to reality.
abstract: The recombinant adeno-associated viral (rAAV) vector is a powerful tool for delivering therapeutic genes into mammalian brains. In rodents and non-human primates, a substantial number of striatal neurons can be transduced with high titer rAAV vectors by simple stereotaxic injection. Efficient and long-term expression of genes for dopamine (DA)-synthesizing enzymes in the striatum restored local DA production and achieved behavioral recovery in animal models of Parkinson's disease (PD). Moreover, sustained expression of a glial cell line-derived neurotrophic factor gene in the striatum rescued nigral neurons and led to functional recovery in a rat model of PD, even when treatment was delayed until after the onset of progressive degeneration. These results suggest that gene therapy using rAAV vectors may become a novel and feasible treatment for PD.
authors.affiliation: Department of Neurology, Jichi Medical School, 3311-1 Yakushiji, Minami-kawachi, Tochigi, Japan 3290498. muramats@jichi.ac.jp
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Muramatsu
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Ikeguchi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Imaharu
authors.initials: I
authors.lastname: Nakano
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D005240:Feasibility Studies; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008252:Macaca fascicularis; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000628:therapy*; D051381:Rats; D020127:Recovery of Function; D019076:Transgenes / Q000235:genetics
chemical_list: C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D004298:Dopamine