脊髓性肌萎缩症的疾病修正治疗  

Disease-modifying therapy for spinal muscular atrophy

作　　者：刘珊 熊晖[1] Liu Shan;Xiong Hui(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院儿科,北京100034

出　　处：《中华实用儿科临床杂志》2023年第6期465-468,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(82171393,81571220);国家重点研发计划(2016YFC0901505);北京市自然科学基金(7212116)。

摘　　要：脊髓性肌萎缩症(SMA)是一种严重的遗传性神经肌肉病,是由于运动神经元存活基因1(SMN1)致病性变异导致的编码产物SMN蛋白缺乏所致。根据患者起病年龄及获得的最大运动功能,SMA分为4个亚型,其中最常见且表型最严重的为SMA1型。自然病程中,大多数SMA1型患儿2岁内死于呼吸衰竭,2~4型患者均有不同程度缓慢进展的肌无力和肌萎缩。疾病修正治疗问世以前,以康复训练、呼吸及营养支持为主的综合治疗是延缓SMA患者病程进展、提高生存率的唯一手段,但由于未从根本上解决SMN蛋白的缺乏,因此患者无法取得运动里程碑的改善。5年来,先后有3种药物获批用于治疗SMA。越来越多的临床试验及真实世界研究数据表明,疾病修正治疗药物可以有效维持各型SMA患者的运动功能,且可促进部分患者获得里程碑进步,显著降低死亡率。但是,不同亚型、病情和病程的患者对药物治疗的反应可能存在明显差异,因此,选择合适的治疗方案,保证患者生活质量尤为重要。本综述主要讨论SMA治疗方面的最新进展及面临的新挑战。Spinal muscular atrophy(SMA)was a severe inherited neuromuscular disease caused by the deficiency of the survival motor neuron(SMN)protein encoded by SMN1 gene with pathogenic variants.According to the age of onset and maximal achievement of motor function,SMA was classified into 4 subtypes.The most common and severe subtype was SMA type 1.During the natural course,most of patients with SMA type 1 die of respiratory failure within 2 years of age if not treated.Patients with other subtypes have progressive muscle weakness and atrophy at varying degrees.Before the emergence of disease-modifying therapy,a multidisciplinary management,including physical therapy,respiratory and nutritional support,has been the only approach to delay the disease progression and enhance the survival rate of SMA.However,motor milestone progress is unable to achieve by SMA patients,because the lack of SMN protein has not been solved.In the past 5 years,3 drugs have been approved for the treatment of SMA.Clinical trials and a growing number of real-world study data have shown that medications of disease-modifying agents contribute to effectively improve motor function in SMA patients with different subtypes,and promote the motor milestone progress in some patients,which significantly reduce the mortality.However,treatment response of disease-modifying agents to SMA varies with the subtypes of SMA,individualized conditions and courses of disease.Therefore,it is particularly important to choose an optimal treatment to ensure the quality of life of patients.This review focuses on recent advances and emerging challenges in the treatment of SMA.

关 键 词：脊髓性肌萎缩症 治疗 进展 不良反应 

分 类 号：R746.4[医药卫生—神经病学与精神病学]