ObjectiveGene therapy by convection‐enhanced delivery of type 2 adeno‐associated virus‐glial cell derived neurotrophic factor (AAV2‐GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD).MethodsA 63‐year‐old man with advanced PD received AAV2‐GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later. An autopsy included brain examination for GDNF transgene expression. Putaminal catecholamine concentrations were compared to in vivo 18F‐Fluorodopa (18F‐FDOPA) positron emission tomography (PET) scanning results before and 18 months after AAV2‐GDNF infusion.ResultsParkinsonian progression stabilized clinically. Postmortem neuropathology confirmed PD. Bilateral putaminal regions previously infused with AAV2‐GDNF expressed the GDNF gene. Total putaminal dopamine was 1% of control, confirming the striatal dopaminergic deficiency suggested by baseline 18F‐DOPA‐PET scanning. Putaminal regions responded as expected to AAV2‐GDNF.ConclusionAfter AAV2‐GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and 18F‐FDOPA‐PET signal, suggesting the regenerative potential of AAV2‐GDNF in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

中文翻译：

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帕金森病患者壳核输注 AAV2-GDNF 45 个月后持续表达 GDNF

目的通过对流增强将 2 型腺相关病毒胶质细胞源性神经营养因子 (AAV2-GDNF) 递送至双侧壳核进行基因治疗，旨在增加GDNF基因表达并治疗帕金森病 (PD)。方法一名患有晚期 PD 的 63 岁男性接受了 AAV2‐GDNF在临床试验中。 45个月后，他在颈椎前路椎间盘切除融合术后死于肺炎。尸检包括脑部检查GDNF转基因表达。壳核儿茶酚胺浓度与体内比较18F-氟多巴（18AAV2 之前和之后 18 个月的 F-FDOPA）正电子发射断层扫描（PET）扫描结果GDNF输注。结果帕金森病进展在临床上稳定。尸检神经病理学证实帕金森病。先前注入 AAV2‐ 的双侧壳核区域GDNF表达了GDNF基因。壳核多巴胺总量为对照的 1%，证实了基线提示的纹状体多巴胺能缺乏18F-DOPA-PET 扫描。壳核区域对 AAV2 的反应符合预期-GDNF.AAV2之后的结论‐GDNF输注，输注壳核区域显示增加GDNF基因表达、酪氨酸羟化酶免疫反应性出芽、儿茶酚水平和18F-FDOPA-PET 信号，表明 AAV2-GDNF 在 PD 中具有再生潜力。 © 2024 作者。运动障碍由 Wiley periodicals LLC 代表国际帕金森和运动障碍协会出版。本文由美国政府雇员撰写，他们的作品在美国属于公共领域。