Article record

机器学习预测非坐立型脊髓性肌萎缩症（SMA）患者对诺西那生钠的治疗反应

Machine learning predicts treatment response to nusinersen in non-sitter spinal muscular atrophy (SMA).

AI/ML耳科IF 3.5Q2

文献信息

PMID	42900957
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Georgia Stimpson 查看其他 11 位作者 Emer O'Reilly；Giorgia Coratti；Deborah Ridout；Tapabrata Chakraborti；Robin Mitra；Roberto de Sanctis；Marika Pane；Mariacristina Scoto；Eugenio Mercuri；Francesco Muntoni；Giovanni Baranello
作者单位	Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK. 查看其他 7 条单位信息 Health and Medical Science Programme, The Alan Turing Institute, London, UK.；NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, London, UK.；Paediatric Neurology Unit, Catholic University, Rome, Italy.；Centro Clinico Nemo, U.O.C. Neuropsichiatria Infantile Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.；Population, Policy & Practice Department, UCL Great Ormond Street Institute of Child Health, London, UK.；UCL Cancer Institute and Dept of Medical Physics & Biomedical Engineering, UCL, London, UK.；Department of Statistical Science, UCL.
期刊	Journal of neuromuscular diseases
SCI 分区	Q2
IF	3.5
研究类型	AI/ML · 临床
所属专科	耳科

中文摘要

背景： 诺西那生钠显著提高了脊髓性肌萎缩症（SMA）患者的生存率并改善了疾病进展。然而，治疗反应存在异质性，部分患者获得坐立和行走能力，而另一些患者的变化则不明显。方法：来自SMA Reach UK和意大利Telethon网络，纳入124例4岁以下接受诺西那生钠治疗的非坐立型SMA患者，并随机分配至训练集和测试集（80/20%）。比较了基于树和回归的生存结局机器学习方法，最终选择斜随机森林，测试集C-Index为0.74。特征从CHOP-INTEND和HINE-2运动功能评估条目、呼吸和吞咽状态中通过互信息进行筛选。结果：62例患者（50%）在中位年龄2.4岁时实现坐立。治疗开始时需要管饲的患者，其预测的中位至坐立时间比不需要管饲者晚4个月，且这是影响最大的因素。特定运动功能特征，包括仰卧位踢腿能力，与更高的坐立可能性强烈相关。结论：本研究提供了一个预测诺西那生钠治疗反应的框架，并代表了SMA治疗计划个性化咨询的第一阶段。资助：SMA Reach的支持由Biogen、Roche和Novartis提供，历史上还得到NIHR BRC、SMA Trust、MRC转化研究中心和MD UK的支持。意大利网络的支持由Famiglie SMA、Telethon（GSP 13002）和ASAMSI提供。

英文摘要

BackgroundNusinersen has substantially increased survival and improved disease progression in Spinal Muscular Atrophy (SMA) patients. However, treatment response is heterogeneous, with some patients gaining the ability to sit and walk whilst others display less obvious changes.MethodFrom the SMA Reach UK and the Italian Telethon Network, 124 non-sitter SMA patients treated with nusinersen under 4 years were included and randomly allocated to training and testing (80/20%). Tree and regression-based machine learning for survival outcomes were compared, and oblique random forests were selected, with a testing C-Index of 0.74. The features were selected from items of the CHOP-INTEND and HINE-2 motor function assessments, respiratory and swallowing status using mutual information.FindingsSixty-two patients (50%) achieved sitting, at a median age of 2.4 years. The predicted median time-to-sitting in those requiring tube feeding at treatment initiation was 4-months later than those without, and this was the most influential factor. Specific motor function features, including the ability to kick in supine, were strongly associated with a higher likelihood of sitting.InterpretationThis work provides a framework for predicting nusinersen-response and represents the first stage in personalised counselling on treatment plans for SMA.FundingSupport for SMA Reach is provided by Biogen, Roche and Novartis, and historically the NIHR BRC, SMA Trust, the MRC Translational Research Centre and MD UK. Support for the Italian network is provided by Famiglie SMA, Telethon (GSP 13002), and ASAMSI.