Abstract：
Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive neuromuscular degeneration resulting from mutations in the survival motor neuron (SMN1) gene. The availability of disease-modifying therapies for SMA therapies highlights the pressing need for easily accessible and cost-effective blood biomarkers to monitor treatment response and for better disease management. Additionally, the wide implementation of newborn genetic screening programs in Western countries enables presymptomatic diagnosis of SMA and immediate treatment administration. However, the absence of monitoring and prognostic blood biomarkers for neurodegeneration in SMA hinders effective disease management. Neurofilament light protein (NfL) is a promising biomarker of neuroaxonal damage in SMA and reflects disease progression in children with SMA undergoing treatment. Recently, the European Medicines Agency issued a letter of support endorsing the potential utilization of NfL as a biomarker of pediatric neurological diseases, including SMA. Within this review, we comprehensively assess the potential applications of NfL as a monitoring biomarker for disease severity and treatment response in pediatric-onset SMA. We provide reference ranges for normal levels of serum based NfL in neurologically healthy children aged 0-18 years. These reference ranges enable accurate interpretation of NfL levels in children and can accelerate the implementation of NfL into clinical practice.
摘要：
脊髓性肌萎缩症（SMA）是婴儿死亡的主要遗传原因，以运动神经元存活（SMN1）基因突变导致的进行性神经肌肉变性为特征。SMA治疗的疾病修饰疗法的可用性凸显了对易于获得且具有成本效益的血液生物标志物的迫切需要，以监测治疗反应和更好的疾病管理。此外,在西方国家，新生儿基因筛查计划的广泛实施使SMA的症状前诊断和立即治疗得以实现。然而,SMA中缺乏神经变性的监测和预后血液生物标志物阻碍了有效的疾病管理。神经丝光蛋白（NfL）是SMA中神经轴突损伤的有希望的生物标志物，并反映了接受治疗的SMA儿童的疾病进展。最近,欧洲药品管理局（EuropeanMedicinesAgency）发布了一封支持信，支持将NfL用作儿科神经系统疾病的生物标志物，包括SMA。在这次审查中，我们全面评估了NfL作为儿科发病SMA疾病严重程度和治疗反应监测生物标志物的潜在应用.我们提供了0-18岁神经系统健康儿童中基于血清NfL正常水平的参考范围。这些参考范围可以准确解释儿童的NfL水平，并可以加快NfL在临床实践中的实施。
