The advent of new therapies in spinal muscular atrophy (SMA) has highlighted the need to have natural history data for comparison. Natural history studies using structured assessments in type I however are very limited. We identified and reviewed all the existing longitudinal history data in infants with type I SMA first assessed before the age of 7 months with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Three longitudinal natural history studies, two performed in the United States and one in Italy, were identified. The different study design of these three studies made it possible for the cumulative dataset to include the full spectrum of severity; from infants with neonatal onset to those with a milder phenotype that were not always included in the individual natural history studies. The cumulative analysis confirmed that, even in a larger cohort, there was never an improvement on the CHOP INTEND over time. This was true for all the infants, irrespective of their age or baseline CHOP INTEND scores. Infants with neonatal onset had low CHOP INTEND scores and a fast decline. The relatively large number of patients allowed us to calculate the rate of progression in subgroups identified according to SMN2 copy number and baseline CHOP INTEND scores. A detailed understanding of the existing data is important, as it will be difficult to acquire new systematic longitudinal history data because of the availability of disease modifying therapies. The cumulative findings in this review help to better understand the variability of natural history data in untreated patients and will be of use for comparison to the real world patients treated with the recently approved therapies that have shown encouraging results in clinical trials.

中文翻译：

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I型脊柱肌肉萎缩症的纵向自然病史：一项重要的评论。

脊髓性肌萎缩症（SMA）的新疗法的出现突显了需要自然史数据进行比较的必要性。但是，使用I型结构化评估的自然史研究非常有限。我们鉴定并回顾了7个月之前首次由费城儿童医院神经肌肉疾病婴儿测试（CHOP INTEND）评估的I型SMA婴儿的所有现有纵向历史数据。确定了三项纵向自然历史研究，其中两项在美国进行，一项在意大利进行。这三项研究的不同研究设计使累积数据集可以涵盖整个严重程度。从初生婴儿到表型较轻的婴儿，并不总是包含在自然史研究中。累积分析证实，即使在较大的队列中，CHOP INTEND也不会随时间而改善。无论年龄或基线CHOP INTEND分数如何，所有婴儿均是如此。新生儿发作的婴儿CHOP INTEND得分低且下降快。相对大量的患者使我们能够计算根据SMN2拷贝数和基线CHOP INTEND分数确定的亚组的进展速度。对现有数据的详细了解很重要，因为由于疾病改良疗法的可用性，将很难获得新的系统性纵向历史数据。