PDF(Pubmed)
Abstract：
Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping in these patients has the potential to be highly therapeutic through restoration of full-length dystrophin expression. We conducted a 48-week open label study of casimersen and golodirsen in 3 subjects with an exon 45 or 53 duplication. Two subjects (aged 18 and 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, and cardiac function appeared stable in the 2 subjects in whom they could be evaluated. Dystrophin expression increased from 0.94 % ±0.59% (mean±SD) of normal to 5.1% ±2.9% by western blot. Percent dystrophin positive fibers also rose from 14% ±17% at baseline to 50% ±42% . Our results provide initial evidence that the use of exon-skipping drugs may increase dystrophin levels in patients with single-exon duplications.
摘要：
在少数Duchenne型肌营养不良患者中，单外显子重复是疾病的原因。这些患者中的外显子跳跃具有通过恢复全长肌营养不良蛋白表达而具有高度治疗性的潜力。我们对3名外显子45或53重复的受试者进行了为期48周的casimersen和golodirsen开放标签研究。两名受试者（年龄为18岁和23岁）在基线时无法走动。上肢,肺,在可以评估的2名受试者中，心功能似乎稳定。通过蛋白质印迹,肌营养不良蛋白表达从正常的0.94%±0.59%(平均值±SD)增加至5.1%±2.9%。肌营养不良蛋白阳性纤维百分比也从基线时的14%±17%上升至50%±42%。我们的结果提供了初步证据，表明使用外显子跳跃药物可能会增加单外显子重复患者的肌营养不良蛋白水平。
