Muramatsu Shin-Ichi, Wang Lijun, Ikeguchi Kunihiko, Fujimoto Ken-Ichi, Nakano Imaharu, Ozawa Keiya
Department of Neurology, Jichi Medical School, 3311-1 Yakushiji, Minami-kawachi, Tochigi, Japan 3290498.
J Neurol. 2002 Sep;249 Suppl 2:II36-40. doi: 10.1007/s00415-002-1207-1.
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.
重组腺相关病毒（rAAV）载体是一种将治疗性基因导入哺乳动物大脑的强大工具。在啮齿动物和非人类灵长类动物中，通过简单的立体定向注射，大量纹状体神经元可以被高滴度rAAV载体转导。在帕金森病（PD）动物模型中，纹状体中多巴胺（DA）合成酶基因的高效长期表达恢复了局部DA的产生，并实现了行为恢复。此外，即使治疗延迟到进行性变性开始后，纹状体中胶质细胞源性神经营养因子基因的持续表达仍能挽救黑质神经元，并导致PD大鼠模型的功能恢复。这些结果表明，使用rAAV载体的基因治疗可能成为一种新颖且可行的PD治疗方法。
