Eteplirsen in the treatment of Duchenne muscular dystrophy.
Eteplirsen in the treatment of Duchenne muscular dystrophy.
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DOI：
10.2147/dddt.s97635
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Yokota T
中科院分区：
文献类型：
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作者：
Lim KR;Maruyama R;Yokota T
杜氏肌营养不良症是一种致命的神经肌肉疾病，大约每3,500-5,000名男婴中就有一人患病，其特征是肌肉进行性恶化。它以x连锁隐性方式遗传，是由编码肌营养不良蛋白的DMD基因的功能丧失突变引起的，肌营养不良蛋白是一种稳定肌肉纤维质膜的细胞骨架蛋白。2016年9月，美国食品和药物管理局（fda）加速批准了eteplirsen（或Exondys 51），该药物通过在缺陷基因变体中特异性跳过51外显子来恢复DMD的翻译阅读框，从而促进肌营养不良蛋白的产生。Eteplirsen适用于约14%的DMD突变患者。本文广泛回顾和讨论了迄今为止关于eteplirsen的可用信息，重点关注临床前和临床试验的药理学、疗效、安全性和耐受性数据。将确定eteplirsen面临的问题，特别是与其功效有关的问题。最后，将讨论eteplirsen和外显子跳跃作为杜氏肌营养不良症治疗的一般治疗策略的地位。
Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500–5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the DMD gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame of DMD through specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients with DMD mutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed.