Blat Yuval, Blat Shachar
Wynnewood, PA, USA
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
J Biomol Screen. 2015 Dec;20(10):1189-203. doi: 10.1177/1087057115586535. Epub 2015 May 14.
Duchenne muscular dystrophy (DMD) is a genetic, lethal, muscle disorder caused by the loss of the muscle protein, dystrophin, leading to progressive loss of muscle fibers and muscle weakness. Drug discovery efforts targeting DMD have used two main approaches: (1) the restoration of dystrophin expression or the expression of a compensatory protein, and (2) the mitigation of downstream pathological mechanisms, including dysregulated calcium homeostasis, oxidative stress, inflammation, fibrosis, and muscle ischemia. The aim of this review is to introduce the disease, its pathophysiology, and the available research tools to a drug discovery audience. This review will also detail the most promising therapies that are currently being tested in clinical trials or in advanced preclinical models.
杜兴氏肌肉营养不良症（DMD）是一种遗传性、致死性的肌肉疾病，由肌肉蛋白肌营养不良蛋白缺失引起，导致肌肉纤维逐渐丧失和肌肉无力。针对DMD的药物研发主要采用两种方法：（1）恢复肌营养不良蛋白的表达或补偿蛋白的表达；（2）减轻下游病理机制，包括钙稳态失调、氧化应激、炎症、纤维化和肌肉缺血。本综述的目的是向药物研发领域的读者介绍该疾病、其病理生理学以及可用的研究工具。本综述还将详细介绍目前正在临床试验或先进临床前模型中进行测试的最有前景的疗法。
