Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Muscle Nerve. 2018 Feb;57(2):193-199. doi: 10.1002/mus.25776. Epub 2017 Sep 18.
The aim of this study was to determine the safety and therapeutic potential of L-carnitine and valproic acid (VPA) in infants with spinal muscular atrophy (SMA).
Our investigation was an open-label phase 2 multicenter trial of L-carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated, matched cohort. Primary outcomes were: safety and adverse events; secondary outcomes were survival, time to death/>16 hours/day of ventilator support; motor outcomes; and maximum ulnar compound motor action potential amplitude.
A total of 245 AEs were observed in 35 of the 37 treated subjects (95%). Respiratory events accounted for 49% of all adverse events, resulting in 14 deaths. Survival was not significantly different between treated and untreated cohorts.
This trial provides evidence that, in infants with SMA type I, L-carnitine/VPA is ineffective at altering survival. The substantial proportion of infants reaching end-points within 6 months of enrollment underscores the urgent need for pre-symptomatic treatment in SMA type I. Muscle Nerve 57: 193-199, 2018.
本研究旨在确定左旋肉碱和丙戊酸（VPA）在脊髓性肌萎缩症（SMA）婴儿中的安全性和治疗潜力。
我们的研究是一项开放性、2 期、多中心左旋肉碱和 VPA 治疗 SMA Ⅰ型婴儿的试验，并与未经治疗的匹配队列进行回顾性比较。主要结果为：安全性和不良事件；次要结果为：生存率、死亡时间（>16 小时/天的呼吸机支持）、运动结果和最大尺神经复合运动动作电位幅度。
在 37 名治疗对象中的 35 名（95%）中观察到 245 例不良事件（AE）。呼吸事件占所有不良事件的 49%，导致 14 例死亡。治疗组和未治疗组的生存率无显著差异。
本试验表明，在 SMA Ⅰ型婴儿中，左旋肉碱/VPA 不能改变生存率。在招募后 6 个月内达到终点的婴儿比例很高，这突显了 SMA Ⅰ型进行症状前治疗的迫切需要。肌肉神经 57: 193-199, 2018.
