This commentary provides an overview of the putamen as an established target site for gene therapy in treating aromatic l-amino acid decarboxylase (AADC) deficiency and Parkinson’s disease, two debilitating neurological disorders that involve motor dysfunction caused by dopamine deficiencies. The neuroanatomy and the function of the putamen in motor control provide good rationales for targeting this brain structure. Additionally, the efficacy and safety of intraputaminal gene therapy demonstrate that restoration of dopamine synthesis in the putamen by using low doses of adeno-associated viral vector serotype 2 to deliver the hAADC gene is well tolerated. This restoration leads to sustained improvements in motor and nonmotor symptoms of AADC deficiency and improved uptake and conversion of exogenous l-DOPA into dopamine in Parkinson’s patients.

中文翻译：

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壳核基因治疗可治疗 AADC 缺乏症和帕金森病


本评论概述了壳核作为基因治疗的既定靶位点，用于治疗芳香族L-氨基酸脱羧酶 (AADC) 缺乏症和帕金森病，这两种神经系统疾病涉及多巴胺缺乏引起的运动功能障碍。神经解剖学和壳核在运动控制中的功能为针对这种大脑结构提供了很好的理论基础。此外，壳核内基因治疗的有效性和安全性表明，通过使用低剂量的腺相关病毒载体血清型2来传递hAADC基因来恢复壳核中的多巴胺合成具有良好的耐受性。这种恢复导致帕金森病患者 AADC 缺乏的运动和非运动症状持续改善，并改善外源性左旋多巴(l -DOPA) 的摄取和转化为多巴胺。