治疗45外显子跳跃突变杜氏肌营养不良症的药物——Casimersen

A new drug for treating Duchenne muscular dystrophy with exon 45 skipping——Casimersen

Casimersen是用于治疗45外显子跳跃突变杜氏肌营养不良症(DMD)的磷酸二酰胺吗啉低聚物(PMO)。DMD是由DMD基因突变导致肌营养不良蛋白缺失引起的。Casimersen可与抗肌萎缩蛋白前mRNA第45外显子结合,从而使mRNA加工过程中排除或跳过该外显子,最终产生一种缩短的、功能性的抗肌萎缩蛋白达到治疗的目的。Casimersen能够为8%适合45外显子跳跃突变的DMD患者提供治疗。临床试验结果表明,接受Casimersen治疗的患者骨骼肌中肌营养不良蛋白的产生增多,且该药物在患者中具有较好的安全性和耐受性。本文对其药物作用机制、药物代谢动力学、药物有效性、药物安全性及用法用量等内容进行总结,旨在为临床用药提供基本参考。

Casimersen(Amondys 45?)is a phosphodiamide morpholine oligomer(PMO)for the treatment of exon 45skipping mutant Duchenne muscular dystrophy(DMD).DMD is caused by mutations in the DMD gene,which resulting in the absence of dystrophin.Casimersen can bind to exon 45 of dystrophin pre-mRNA,thus,the exon is excluded or skipped during mRNA processing,eventually producing a shortened,functional dystrophin for therapeutic purposes.Casimersen is able to treat 8%of DMD patients with exon 45 skipping mutations.Clinical trial results showed that patients treated with Casimersen had increased dystrophin production in skeletal muscle,and the drug was safe and well tolerated.This article summarized its drug action mechanism,pharmacokinetics,efficacy,safety,and usage,aiming to provide a basic reference for clinical drug use.