PDF(Pubmed)
Abstract：
Duchenne Muscular Dystrophy (DMD) includes predictable phases requiring dedicated standard treatments. Therapeutic strategies feature corticosteroids or the more recent gene therapy/stop codon read-through. Ataluren (Translarna®) is an oral drug promoting the readthrough of premature stop codons caused by nonsense mutation (nm) in order to produce full-length dystrophin. It was licensed by EMA in 2014 for ambulatory patients with nmDMD aged ≥ 5 years. Our aim is to report data on long-term ataluren use in Italian patients with nmDMD, with emphasis on continuity of the treatment after loss of ambulation (LoA). Four DMD patients aged between 16 and 24 years who lost ambulation between 12 and 14 years continued to take ataluren after LoA. The oldest patient, aged 24 years, is still taking a few steps. Even in those experiencing motor decline, PUL-test performances were stable and respiratory function satisfactory in all; two patients developed severe cardiomyopathy, stable in one. Therapeutic continuity with ataluren should be offered to all nmDMD patients after LoA given its favourable safety and efficacy profile. However, further research is recommended to identify additional clinically meaningful outcomes and treatment goals following LoA.
摘要：
杜氏肌营养不良症(DMD)包括需要专用标准治疗的可预测阶段。治疗策略的特点是皮质类固醇或最近的基因治疗/终止密码子通读。Ataluren（Translarna®）是一种口服药物，可促进由无义突变（nm）引起的过早终止密码子的连读，以产生全长肌营养不良蛋白。2014年获得EMA许可，适用于年龄≥5岁的非卧床nmDMD患者。我们的目的是报告意大利nmDMD患者长期使用ataluren的数据，强调失去行走(LoA)后治疗的连续性。四名年龄在16至24岁之间的DMD患者在12至14岁之间失去了行走能力，在LoA后继续服用ataluren。最老的病人,24岁,仍在采取一些步骤。即使在那些运动衰退的人中，所有患者的PUL测试表现稳定，呼吸功能令人满意；两名患者发展为严重心肌病，稳定在一个鉴于LoA具有良好的安全性和有效性，应在LoA后向所有nmDMD患者提供ataluren的治疗连续性。然而,建议进一步研究以确定LoA后其他有临床意义的结局和治疗目标.
