Disease-modifying therapy for spinal muscular atrophy / 中华实用儿科临床杂志

ABSTRACT

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.