PDF(Pubmed)
Abstract：
This longitudinal cohort study aimed to determine whether circulating neurofilaments (NFs) can monitor response to molecular therapies in newborns with spinal muscular atrophy (SMA; NCT02831296). We applied a mixed-effect model to examine differences in serum NF levels among healthy control infants (n = 13), untreated SMA infants (n = 68), and SMA infants who received the genetic therapies nusinersen and/or onasemnogene abeparvovec (n = 22). Increased NF levels were inversely associated with SMN2 copy number. SMA infants treated with either nusinersen or onasemnogene abeparvovec achieved important motor milestones not observed in the untreated cohort. NF levels declined more rapidly in the nusinersen cohort as compared with the untreated cohort. Unexpectedly, those receiving onasemnogene abeparvovec monotherapy showed a significant rise in NF levels regardless of SMN2 copy number. In contrast, symptomatic SMA infants who received nusinersen, followed by onasemnogene abeparvovec within a short interval after, did not show an elevation in NF levels. While NF cannot be used as the single marker to predict outcomes, the elevated NF levels observed with onasemnogene abeparvovec and its absence in infants treated first with nusinersen may indicate a protective effect of co-therapy during a critical period of vulnerability to acute denervation.
摘要：
这项纵向队列研究旨在确定循环神经丝（NFs）是否可以监测患有脊髓性肌萎缩症的新生儿对分子疗法的反应（SMA;NCT02831296）。我们应用混合效应模型来检查健康对照婴儿（n=13）之间血清NF水平的差异，未经治疗的SMA婴儿（n=68），接受nusinersen和/或asemnogeneabeparvovec基因治疗的SMA婴儿（n=22）。增加的NF水平与SMN2拷贝数成反比。接受nusinersen或onasemnogeneabeparvovec治疗的SMA婴儿达到了未治疗队列中未观察到的重要运动里程碑。与未处理的队列相比，nusinersen队列中NF水平下降更快。出乎意料的是,无论SMN2拷贝数如何,接受onasemnogeneabeparvovec单药治疗的患者NF水平均显著升高.相比之下,接受nusinersen的有症状的SMA婴儿，紧随其后的是一个短暂的间隔内的asemnogeneabeparvovec，没有显示NF水平升高。虽然NF不能用作预测结果的单一标记，在首先接受nusinersen治疗的婴儿中观察到的NF水平升高和不存在NF水平升高可能表明在急性去神经支配易感的关键时期联合治疗具有保护作用.
