帕金森病患者纹状体注射 AAV2-GDNF45 个月后持续表达 GDNF。
Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.
机构信息
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Laboratory of Pathology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
出版信息
Mov Disord. 2024 Aug;39(8):1412-1417. doi: 10.1002/mds.29820. Epub 2024 May 8.
OBJECTIVE
Gene 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).
METHODS
A 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 F-Fluorodopa (F-FDOPA) positron emission tomography (PET) scanning results before and 18 months after AAV2-GDNF infusion.
RESULTS
Parkinsonian 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 F-DOPA-PET scanning. Putaminal regions responded as expected to AAV2-GDNF.
CONCLUSION
After AAV2-GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and F-FDOPA-PET signal, suggesting the regenerative potential of AAV2-GDNF in PD.
目的
通过对流增强递送来实现脑源性神经营养因子（GDNF）的基因治疗，将 2 型腺相关病毒（AAV2-GDNF）递送至双侧壳核，旨在增加 GDNF 基因表达并治疗帕金森病（PD）。
方法
一名 63 岁的晚期 PD 男性患者参加了一项临床试验，接受了 AAV2-GDNF 的治疗。45 个月后，他因前颈椎间盘切除术和融合术后肺炎去世。尸检包括对 GDNF 转基因表达的脑检查。将 AAV2-GDNF 输注前后 18 个月的活体氟多巴（F-FDOPA）正电子发射断层扫描（PET）扫描结果与壳核儿茶酚胺浓度进行比较。
结果
帕金森病的临床进展稳定。死后神经病理学证实为 PD。先前用 AAV2-GDNF 输注的双侧壳核区域表达了 GDNF 基因。总壳核多巴胺为对照的 1%，证实了基线 F-DOPA-PET 扫描提示的纹状体多巴胺能缺乏。壳核区域对 AAV2-GDNF 的反应如预期的那样。
结论
在 AAV2-GDNF 输注后，输注的壳核区域显示出 GDNF 基因表达增加、酪氨酸羟化酶免疫反应性发芽、儿茶酚胺水平和 F-FDOPA-PET 信号增加，表明 AAV2-GDNF 在 PD 中的再生潜力。
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