Toward an Oligonucleotide Therapy for Duchenne Muscular Dystrophy: A Complex Development Challenge
Toward an Oligonucleotide Therapy for Duchenne Muscular Dystrophy: A Complex Development Challenge
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DOI：
10.1126/scitranslmed.3000512
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发表时间：
2010-03-31
影响因子：
17.1
通讯作者：
Wood, Matthew J. A.
中科院分区：
文献类型：
--
作者：
Wood, Matthew J. A.
反义寡核苷酸（AO）介导的外显子跳跃是治疗杜氏肌营养不良症（DMD）的一种有前途的新疗法，最近证明了恢复DMD患者中缺失的肌营养不良蛋白的原理。然而，可用于外显子跳跃的AO化学的范围是有限的;有效的系统性肌营养不良蛋白蛋白恢复尚未得到证实，并且将需要患者的疾病修饰;并且目前的方法是突变特异性的，需要开发多种AO药物来治疗所有DMD患者。因此，这是一个高度复杂的药物开发挑战。
Antisense oligonucleotide (AO)-mediated exon skipping is a promising new therapy for Duchenne muscular dystrophy (DMD), recently demonstrating proof of principle for restoring the absent dystrophin protein in DMD patients. However, the range of AO chemistries available for exon skipping is limited; effective systemic dystrophin protein restoration has yet to be demonstrated and will be required for disease modification in patients; and the current approach is mutation-specific, necessitating the development of multiple AO drugs to treat all DMD patients. This is therefore a highly complex drug development challenge.