脊髓性肌萎缩症治疗药物研究进展

A review of advances in spinal muscular atrophy treatment agents

目的介绍脊髓性肌萎缩症(spinal muscular atrophy,SMA)治疗药物研究进展,为新药开发提供思路。方法检索2013—2022年国内外与SMA发病机制和相关药物有关的文献,进行归纳总结。结果SMA是一种由运动神经元存活(survival motor neuron,SMN)基因1的纯合缺失或突变引起的遗传性神经肌肉疾病,主要表现为肌无力。药物主要通过干预剪切、递送完整SMN1基因及神经保护的途径进行治疗,且疾病表型与钙离子之间存在潜在关系,需要进一步探索。结论对现有药物的研究,有助于深入了解疾病机制以及药物的作用方式,为药物开发奠定基础。

Objective To introduce the progress of medications used to treat spinal muscular atrophy(SMA),and to provide ideas for the research of new medications.Methods The literatures about the mechanism and treatment medications of SMA were retrieved and summarized.Results SMA is an inherited neuromuscular disease arising from homozygous loss or mutation of the survival motor neuron gene(SMN1),the main symptom is muscle weakness,medications work by altering splicing and cutting,delivering SMN1 gene copies into cells or neuroprotection.Moreover,Ca2+was found to have the potential relationship with disease phenotype.Existing researches are mainly based on the abovementioned patterns and targets.Conclusion The comprehension of existing medications helps us to understand the mechanism of disease and the way medications work,which lays the foundation for drug development.