Rodino-Klapac Louise R, Chicoine Louis G, Kaspar Brian K, Mendell Jerry R
Center for Gene Therapy, Columbus Children's Research Institute, Columbus, OH, USA.
Arch Neurol. 2007 Sep;64(9):1236-41. doi: 10.1001/archneur.64.9.1236.
Duchenne muscular dystrophy is a debilitating X-linked disease with limited treatment options. We examined the possibility of moving forward with gene therapy, an approach that demonstrates promise for treating Duchenne muscular dystrophy. Gene therapy is not limited to replacement of defective genes but also includes strategies using surrogate genes with alternative but effective means of improving cellular function or repairing gene mutations. The first viral-mediated gene transfer for any muscle disease was carried out at Columbus Children's Research Institute and Ohio State University for limb girdle muscular dystrophy type 2D, and the first viral-mediated trial of gene transfer for Duchenne muscular dystrophy is under way at the same institutions. These studies, consisting of intramuscular injection of virus into a single muscle, are limited in scope and represent phase 1 clinical trials with safety as the primary end point. These initial clinical studies lay the foundation for future studies, providing important information about dosing, immunogenicity, and viral serotype in humans. This article highlights the challenges and potential pitfalls as the field advances this treatment modality to clinical reality.
杜氏肌营养不良症是一种使人衰弱的X连锁疾病，治疗选择有限。我们研究了推进基因治疗的可能性，这种方法显示出治疗杜氏肌营养不良症的前景。基因治疗不仅限于替换缺陷基因，还包括使用替代基因的策略，这些替代基因采用其他有效手段来改善细胞功能或修复基因突变。首次针对任何肌肉疾病进行的病毒介导基因转移是在哥伦布儿童研究所和俄亥俄州立大学针对2D型肢带型肌营养不良症开展的，而首次针对杜氏肌营养不良症的病毒介导基因转移试验正在同一机构进行。这些研究包括将病毒肌肉注射到单个肌肉中，范围有限，属于以安全性为主要终点的1期临床试验。这些初步临床研究为未来研究奠定了基础，提供了关于人体给药、免疫原性和病毒血清型的重要信息。本文强调了随着该领域将这种治疗方式推向临床实际所面临的挑战和潜在陷阱。
