Cooper Katy, Nalbant Gamze, Sutton Anthea, Harnan Sue, Thokala Praveen, Chilcott Jim, McNeill Alisdair, Bessey Alice
School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK.
Int J Neonatal Screen. 2024 Aug 14;10(3):56. doi: 10.3390/ijns10030056.
Spinal muscular atrophy (SMA) causes the degeneration of motor neurons in the spinal cord. Treatments including nusinersen, risdiplam, and onasemnogene abeparvovec have been shown to be effective in reducing symptoms, with recent studies suggesting greater effectiveness when treatment is initiated in the presymptomatic stage. This systematic review synthesises findings from prospective studies of presymptomatic treatment for 5q SMA published up to December 2023. The review identified three single-arm interventional studies of presymptomatic treatment (NURTURE, RAINBOWFISH, and SPR1NT), six observational studies comparing presymptomatic or screened cohorts versus symptomatic cohorts, and twelve follow-up studies of screened cohorts only (i.e., babies identified via newborn screening for SMA). Babies with three copies met most motor milestones in the NURTURE study of nusinersen and in the SPR1NT study of onasemnogene abeparvovec. Babies with two copies in these two studies met most motor milestones but with some delays, and some required ventilatory or feeding support. The RAINBOWFISH study of risdiplam is ongoing. Naïve comparisons of presymptomatic treatment in SPR1NT, versus untreated or symptomatic treatment cohorts, suggested improved outcomes in patients treated presymptomatically. Comparative observational studies supported the finding that presymptomatic treatment, and early treatment following screening, may improve outcomes compared with treatment at the symptomatic stage. Further research should assess the long-term clinical outcomes and cost-effectiveness of presymptomatic treatment for SMA.
脊髓性肌萎缩症（SMA）会导致脊髓中的运动神经元退化。包括诺西那生钠、利司扑兰和onasemnogene abeparvovec在内的治疗方法已被证明在减轻症状方面有效，最近的研究表明，在症状前阶段开始治疗时效果更佳。本系统评价综合了截至2023年12月发表的关于5q SMA症状前治疗的前瞻性研究结果。该评价确定了三项症状前治疗的单臂干预研究（NURTURE、RAINBOWFISH和SPR1NT）、六项比较症状前或筛查队列与症状队列的观察性研究，以及仅针对筛查队列（即通过新生儿SMA筛查确定的婴儿）的十二项随访研究。在诺西那生钠的NURTURE研究和onasemnogene abeparvovec的SPR1NT研究中，携带三个拷贝的婴儿达到了大多数运动里程碑。在这两项研究中，携带两个拷贝的婴儿达到了大多数运动里程碑，但有一些延迟，一些婴儿需要通气或喂养支持。利司扑兰的RAINBOWFISH研究正在进行中。SPR1NT中症状前治疗与未治疗或症状性治疗队列的简单比较表明，症状前治疗的患者预后有所改善。比较观察性研究支持了这一发现，即与症状期治疗相比，症状前治疗和筛查后的早期治疗可能会改善预后。进一步的研究应评估SMA症状前治疗的长期临床结果和成本效益。
