磁共振引导的壳核基因治疗晚期帕金森病试验
Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson's disease
本研究评估了磁共振引导下对流增强递送 AAV2-GDNF 至晚期帕金森病患者双侧壳核的安全性和耐受性。13 名患者接受递增剂量注射，术中 MRI 监测分布。治疗无临床或影像学毒性，平均壳核覆盖率为 26%。UPDRS 评分保持稳定，10/13 和 12/13 的患者在 6 和 18 个月时 [18F]FDOPA 摄取增加。结果表明该递送方式安全，并提示对多巴胺能神经元有神经营养效应，但未显示显著临床改善。
为什么推荐给您：AAV2-GDNF 壳核注射的 1 期安全性试验，未达主要临床疗效终点，属常规早期试验。
不需要生物学背景，多打比方
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摘要Abstract
OBJECTIVE: To investigate the safety and tolerability of convection-enhanced delivery of an adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor into the bilateral putamina of PD patients.
METHODS: Thirteen adult patients with advanced PD underwent adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor and gadoteridol (surrogate MRI tracer) coinfusion (450 μL/hemisphere) at escalating doses: 9 × 10^10 vg (n = 6); 3 × 10^11 vg (n = 6); and 9 × 10^11 vg (n = 1). Intraoperative MRI monitored infusion distribution. Patients underwent UPDRS assessment and [18 F]FDOPA-PET scanning preoperatively and 6 and 18 months postoperatively.
RESULTS: Adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor was tolerated without clinical or radiographic toxicity. Average putaminal coverage was 26%. UPDRS scores remained stable. Ten of thirteen and 12 of 13 patients had increased [18 F]FDOPA Kis at 6 and 18 months postinfusion (increase range: 5-274% and 8-130%; median, 36% and 54%), respectively. Ki differences between baseline and 6- and 18-month follow-up were statistically significant (P < 0.0002).
CONCLUSION: Adeno-associated virus, serotype-2 vector carrying glial cell line-derived neurotrophic factor infusion was safe and well tolerated. Increased [18 F]FDOPA uptake suggests a neurotrophic effect on dopaminergic neurons. © 2019 International Parkinson and Movement Disorder Society.