Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy
Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy
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DOI：
10.1016/j.pediatrneurol.2019.05.005
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发表时间：
2019-09-01
影响因子：
3.8
通讯作者：
Mendell, Jerry
中科院分区：
文献类型：
--
作者：
Lowes, Linda P.;Alfano, Lindsay N.;Mendell, Jerry
背景：这项研究描述了早期使用AVXS-101(Onasemnogene Abparvovec)基因替代疗法治疗1型严重脊肌萎缩症(SMA1)后的运动功能反应。方法：这项研究是对12名在1期开放研究(NCT02122952)中接受AVXS-101治疗剂量的严重脊肌萎缩症(SMA1)婴儿的随访分析。根据服药时的年龄和基线将婴儿分组：(1)早期服药/低运动量，服药年龄<3个月，得分=20(n=3)。结果：早期服药/低运动量组平均增加35.0分，平均基线15.7分，而晚期服药组平均增加23.3分，平均基线26.5分。早期剂量/高运动组的平均得分很快达到60.3，接近最大评分()，从平均基线44.0分开始。尽管基线运动评分较低，但早期服药/低运动量组比晚服药组更早实现无辅助坐姿(平均年龄：17.0比22.0个月)。早期剂量/高运动组最早达到这一里程碑(平均年龄：9.4个月)。结论：早期使用AVXS-101治疗重度SMA1的婴儿运动能力迅速显著改善，突显了新生儿筛查和早期治疗的重要性，并证明了AVXS-101的治疗潜力，无论基线运动功能如何。(C)2019年提交人。由爱思唯尔公司出版。
Background: This study characterizes motor function responses after early dosing of AVXS-101 (onasemnogene abeparvovec) in gene replacement therapy in infants with severe spinal muscular atrophy type 1 (SMA1).Methods: This study is a follow-up analysis of 12 infants with SMA1 who received the proposed therapeutic dose of AVXS-101 in a Phase 1 open-label study (NCT02122952). Infants were grouped according to age at dosing and baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores: (1) early dosing/low motor, dosed age less than three months with scores = 20 (n = 3).Results: Early dosing/low motor group demonstrated a mean gain of 35.0 points from a mean baseline of 15.7, whereas the late dosing group had a mean gain of 23.3 from a mean baseline of 26.5. The early dosing/high motor group quickly reached a mean score of 60.3, near the scale maximum (64), from a mean baseline of 44.0. Despite a lower baseline motor score, the early dosing/low motor group achieved sitting unassisted earlier than the late dosing group (mean age: 17.0 vs 22.0 months). The early dosing/high motor group reached this milestone earliest (mean age: 9.4 months).Conclusions: The rapid, significant motor improvements among infants with severe SMA1 treated with AVXS-101 at an early age highlight the importance of newborn screening and early treatment and demonstrate the therapeutic potential of AVXS-101 regardless of baseline motor function. (C) 2019 The Authors. Published by Elsevier Inc.