Voisin Vincent, de la Porte Sabine
Laboratoire de Neurobiologie Cellulaire et Moléculaire, 91198 Gif sur Yvette, France.
Int Rev Cytol. 2004;240:1-30. doi: 10.1016/S0074-7696(04)40001-1.
Duchenne muscular dystrophy (DMD), a severe X-linked genetic disease affecting one in 3500 boys, is the most common myopathy in children. DMD is due to a lack of dystrophin, a submembrane protein of the cytoskeleton, which leads to the progressive degeneration of skeletal, cardiac, and smooth muscle tissue. A milder form of the disease, Becker muscular dystrophy (BMD), is characterized by the presence of a semifunctional truncated dystrophin, or reduced levels of full-length dystrophin. DMD is the focus of three different supportive or therapeutic approaches: gene therapy, cell therapy, and drug therapy. Here we consider these approaches in terms of three potential goals: improvement of dystrophic phenotype, expression of dystrophin, and overexpression of utrophin. Utrophin exhibits 80% homology with dystrophin and is able to perform similar functions. Pharmacological strategies designed to overexpress utrophin appear promising and may circumvent many obstacles to gene and cell-based therapies.
杜兴氏肌肉营养不良症（DMD）是一种严重的X连锁遗传病，每3500名男孩中就有1人患病，是儿童中最常见的肌病。DMD是由于缺乏肌营养不良蛋白，一种细胞骨架的膜下蛋白，这导致骨骼肌、心肌和平滑肌组织的进行性退化。该疾病的一种较轻形式，贝克氏肌肉营养不良症（BMD），其特征是存在半功能性截短的肌营养不良蛋白，或全长肌营养不良蛋白水平降低。DMD是三种不同支持或治疗方法的重点：基因治疗、细胞治疗和药物治疗。在这里，我们根据三个潜在目标来考虑这些方法：改善营养不良表型、肌营养不良蛋白的表达和肌养蛋白的过表达。肌养蛋白与肌营养不良蛋白有80%的同源性，并且能够执行类似的功能。旨在使肌养蛋白过表达的药理学策略似乎很有前景，并且可能规避基于基因和细胞的疗法的许多障碍。
