Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex
Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex
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DOI：
10.1089/hum.1998.9.7-1093
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发表时间：
1998-05-01
影响因子：
4.2
通讯作者：
Nagatsu, T
中科院分区：
文献类型：
--
作者：
Imaoka, T;Date, I;Nagatsu, T
作为病毒介导的基因转移的替代方法，我们之前证明了一种简单、安全、有效的外源基因转移到中枢神经系统的方法，即连续注射质粒dna -阳离子脂质体复合物。为探索该方法是否可应用于某些神经系统疾病的治疗，本研究采用帕金森病（PD）实验模型，连续注射7天后，将牛乳头瘤病毒质粒载体携带的酪氨酸羟化酶（TH）和芳香l -氨基酸脱羧酶（AADC）基因高效导入6-羟多巴胺损伤大鼠纹状体胶质细胞。转染TH基因后，阿帕吗啡诱导的PD模型旋转行为明显恢复，且这种效果持续至注射后5周。此外，通过这种方法可以很容易地完成TH与AADC基因的共转染，并且与单独转染TH基因相比，可以更大更持久地改善阿帕吗啡诱导的旋转行为。我们认为，这种方法是一种可控的和可管理的替代其他方法的基因治疗PD。
As an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid DNA-cationic liposome complex. To explore whether this approach can be applied to the treatment of certain neurological disorders, we used an experimental model of Parkinson's disease (PD) in the present study, Following continuous injection for 7 days, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes carried by a bovine papilloma virus-based plasmid vector were efficiently introduced into glial cells in the striatum of 6-hydroxydopamine-lesioned rats. Significant recovery in apomorphine-induced rotational behavior of PD models was obtained by transfection of TH gene and this effect continued for up to 5 weeks after injection. Moreover, cotransfection of TH with AADC genes was readily accomplished by this procedure and resulted in a greater and longer-lasting improvement of apomorphine-induced rotational behavior than was achieved by transfection of TH gene alone. We suggest that this approach is a controllable and manageable alternative to other methods of gene therapy for the treatment of PD.