Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Curr Opin Neurol. 2012 Oct;25(5):588-96. doi: 10.1097/WCO.0b013e328357b0be.
Duchenne muscular dystrophy is a severe neuromuscular disorder for which there is currently no cure. Years of research have come to fruition during the past 18 months with publications on clinical trials for several gene therapy approaches for Duchenne muscular dystrophy. This review covers the present status of these approaches.
The exon skipping approach is most advanced in the process of clinical application. Encouraging results have been obtained in two systemic clinical trials and further optimization has increased delivery to the heart in animal models. Limitations of the approach are the mutation-specificity and the anticipated requirement for lifelong treatment. Gene therapy by means of gene transfer holds the promise of more long-lasting effects. Results of a first, early-stage gene therapy trial, using viral vectors to deliver a minidystrophin gene, were reported. Animal studies suggest that it may be possible to overcome the main challenges currently facing gene therapy (immunogenicity of the vector and systemic body-wide delivery).
Significant steps have been made in the development of gene therapy approaches for Duchenne muscular dystrophy. These approaches aim to slow down disease progression, requiring robust outcome measures to assess efficacy.
目前尚无治疗杜氏肌营养不良症的方法，这种严重的神经肌肉疾病仍亟待攻克。在过去的 18 个月中，多项临床试验对多种杜氏肌营养不良症的基因治疗方法进行了研究并取得了成果。本文综述了这些方法的现状。
外显子跳跃方法在临床应用中最为先进。两项系统临床试验取得了令人鼓舞的结果，进一步优化提高了心脏的转导效率。该方法的局限性在于其突变特异性和预期的终身治疗需求。基因转移的基因治疗有望产生更持久的效果。使用病毒载体传递微小肌营养不良蛋白基因的首次早期基因治疗试验的结果已经公布。动物研究表明，有可能克服基因治疗目前面临的主要挑战（载体的免疫原性和全身系统传递）。
在开发杜氏肌营养不良症的基因治疗方法方面已经取得了重大进展。这些方法旨在减缓疾病进展，需要强有力的结果测量来评估疗效。
