Mohanlal Smilu, Mubeena P M, Hussain Hafsa, Anand Manjula, Kumar Satish, Ashraf V V, Rabia Tajimal A, Janardhanan Sujith, Kumar Suresh
Department of Pediatric Neurology, Aster Malabar Institute of Medical Sciences, Kozhikode, Kerala, India.
Department of Pediatrics, Aster Malabar Institute of Medical Sciences, Kozhikode, Kerala, India.
Ann Indian Acad Neurol. 2025 Jul 1;28(4):547-553. doi: 10.4103/aian.aian_670_24. Epub 2025 Aug 7.
Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder that leads to anterior horn cell loss. Recent advancements in disease-modifying therapies (DMTs) offer promising new treatment options. This study aimed to evaluate and compare the efficacy and safety profiles of risdiplam, nusinersen, and gene therapy in SMA patients with different disease severities in an Indian cohort.
An observational retrospective study was conducted between June 2020 and October 2023, involving 47 genetically confirmed SMA patients (types 1-3). Participants received treatment with risdiplam (n = 11), nusinersen (Spinraza) (n = 25), gene therapy (n = 9), and combination therapy/bridging with risdiplam and gene therapy (n = 2). Motor function was assessed using the Hammersmith functional motor scale expanded (HFMSE) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders over 6 monthly follow-up intervals. Safety was monitored by tracking adverse events. As the majority were SMA types 2/3, the primary outcome was measured using HFMSE scores, with improvement defined as an absolute change in HFMSE score of ≥3 points from the baseline (first visit) to the third visit (completion of 12 months).
There were 47 patients aged 1-23 years (28 girls and 19 boys), who received various DMTs, with a minimum of three visits considered for analysis. All treatments resulted in motor function improvements. Gene therapy showed the most substantial benefit, with a median HFMSE score increase of 4 (2-15) compared to 3.5 (0-7.25) for nusinersen and 2.5 (0.25-8.0) for risdiplam. A positive correlation was observed between the number of SMN2 copies and baseline disease severity (Spearman's correlation = 0.57; P = 0.001). Safety profiles were consistent across all therapies, with no new concerns.
This study underscores the efficacy of contemporary SMA treatments and highlights the potential benefits of personalized treatment strategies, despite variability in disease severity. Future research should focus on optimizing individualized therapy approaches.
脊髓性肌萎缩症（SMA）是一种进行性神经肌肉疾病，会导致前角细胞丧失。疾病修饰疗法（DMTs）的最新进展提供了有前景的新治疗选择。本研究旨在评估和比较利司扑兰、诺西那生和基因疗法在印度队列中不同疾病严重程度的SMA患者中的疗效和安全性。
在2020年6月至2023年10月期间进行了一项观察性回顾性研究，纳入47例基因确诊的SMA患者（1 - 3型）。参与者接受了利司扑兰治疗（n = 11）、诺西那生（Spinraza）治疗（n = 25）、基因疗法治疗（n = 9）以及利司扑兰与基因疗法的联合治疗/桥接治疗（n = 2）。在6个每月一次的随访间隔中，使用扩展的哈默史密斯功能运动量表（HFMSE）和费城儿童医院婴儿神经肌肉疾病测试评估运动功能。通过跟踪不良事件监测安全性。由于大多数为2/3型SMA，主要结局使用HFMSE评分进行测量，改善定义为从基线（首次就诊）到第三次就诊（完成12个月）时HFMSE评分的绝对变化≥3分。
有47例年龄在1 - 23岁的患者（28名女孩和19名男孩）接受了各种DMTs治疗，至少考虑三次就诊进行分析。所有治疗均导致运动功能改善。基因疗法显示出最大的益处，HFMSE评分中位数增加4（2 - 15），而诺西那生为3.5（0 - 7.25），利司扑兰为2.5（0.25 - 8.0）。观察到SMN2拷贝数与基线疾病严重程度之间存在正相关（斯皮尔曼相关性 = 0.57；P = 0.001）。所有疗法的安全性概况一致，未出现新的问题。
本研究强调了当代SMA治疗的疗效，并突出了个性化治疗策略的潜在益处，尽管疾病严重程度存在差异。未来的研究应专注于优化个体化治疗方法。
