From the Departments of Neurology (C.W.C.) and Neurological Surgery (M.E.T., K.S.B., P.S.L.), University of California, San Francisco; Department of Neurosurgery (R.M.R.), Massachusetts General Hospital; Harvard Medical School (R.M.R.), Boston, MA; Department of Neurology (A.D.V.L.), University of Pittsburgh Medical Center, PA; Brain Neurotherapy Bio (A.D.V.L.), Inc., Columbus, OH; Voyager Therapeutics, Inc. (E.M.F., O.S.K., C.L., A.M.), Cambridge, MA; Neurocrine Biosciences, Inc. (G.S.L., E.W.R.), San Diego, CA; ApotheCom (M.L.P., J.R.R.), New York, NY; and Department of Neurological Surgery (K.S.B.), Ohio State University, Columbus.
Neurology. 2022 Jan 4;98(1):e40-e50. doi: 10.1212/WNL.0000000000012952. Epub 2021 Oct 14.
To report final, 36-month safety and clinical outcomes from the PD-1101 trial of NBIb-1817 (VY-AADC01) in participants with moderately advanced Parkinson disease (PD) and motor fluctuations.
PD-1101 was a phase 1b, open-label, dose escalation trial of VY-AADC01, an experimental AAV2 gene therapy encoding the human aromatic l-amino acid decarboxylase (AADC) enzyme. VY-AADC01 was delivered via bilateral, intraoperative MRI-guided putaminal infusions to 3 cohorts (n = 5 participants per cohort): cohort 1, ≤7.5 × 10 vector genomes (vg); cohort 2, ≤1.5 × 10 vg; cohort 3, ≤4.7 × 10 vg.
No serious adverse events (SAEs) attributed to VY-AADC01 were reported. All 4 non-vector-related SAEs (atrial fibrillation and pulmonary embolism in 1 participant and 2 events of small bowel obstruction in another participant) resolved. Requirements for PD medications were reduced by 21%-30% in the 2 highest dose cohorts at 36 months. Standard measures of motor function (PD diary, Unified Parkinson's Disease Rating Scale III "off"-medication and "on"-medication scores), global impressions of improvement (Clinical Global Impression of Improvement, Patient Global Impression of Improvement), and quality of life (39-item Parkinson's Disease Questionnaire) were stable or improved compared with baseline at 12, 24, and 36 months following VY-AADC01 administration across cohorts.
VY-AADC01 and the surgical administration procedure were well-tolerated and resulted in stable or improved motor function and quality of life across cohorts, as well as reduced PD medication requirements in cohorts 2 and 3 over 3 years.
NCT01973543.
This study provides Class IV evidence that, in patients with moderately advanced PD and motor fluctuations, putaminal infusion of VY-AADC01 is well tolerated and may improve motor function.
报告 NBIb-1817（VY-AADC01）在中重度帕金森病（PD）和运动波动患者中的 PD-1101 试验的最终 36 个月安全性和临床结果。
PD-1101 是一项 1b 期、开放性、剂量递增的 VY-AADC01 试验，VY-AADC01 是一种实验性的 AAV2 基因治疗药物，编码人类芳香族 l-氨基酸脱羧酶（AADC）酶。VY-AADC01 通过双侧、术中 MRI 引导的豆状核输注递送至 3 个队列（每个队列 5 名参与者）：队列 1，≤7.5×10 个载体基因组（vg）；队列 2，≤1.5×10 vg；队列 3，≤4.7×10 vg。
未报告与 VY-AADC01 相关的任何严重不良事件（SAE）。所有 4 例非载体相关 SAE（1 例患者发生心房颤动和肺栓塞，另 1 例患者发生 2 例小肠梗阻事件）均已解决。在 36 个月时，最高 2 个剂量队列的 PD 药物需求减少了 21%-30%。运动功能的标准测量（PD 日记、统一帕金森病评定量表 III“关”药和“开”药评分）、整体改善印象（临床整体印象改善、患者整体印象改善）以及生活质量（39 项帕金森病问卷）在 VY-AADC01 给药后 12、24 和 36 个月在各个队列中均与基线相比保持稳定或改善。
VY-AADC01 和手术给药程序具有良好的耐受性，在各个队列中均导致运动功能和生活质量稳定或改善，并且在 3 年内，2 队列和 3 队列的 PD 药物需求减少。
NCT01973543。
本研究提供了 IV 级证据，表明在中重度 PD 和运动波动患者中，豆状核内输注 VY-AADC01 具有良好的耐受性，并可能改善运动功能。
Zotero 插件
