Tinsley J M, Potter A C, Phelps S R, Fisher R, Trickett J I, Davies K E
Genetics Laboratory, Department of Biochemistry, Oxford, UK.
Nature. 1996 Nov 28;384(6607):349-53. doi: 10.1038/384349a0.
Duchenne muscular dystrophy (DMD) is a severe, progressive muscle-wasting disease that causes cardiac or respiratory failure and results in death at about 20 years of age. Replacement of the missing protein, dystrophin, using myoblast transfer in humans or viral/liposomal delivery in the mouse DMD model is inefficient and short-lived. One alternative approach to treatment would be to upregulate the closely related protein, utrophin, which might be able to compensate for the dystrophin deficiency in all relevant muscles. As a first step to this approach, we have expressed a utrophin transgene at high levels in the dystrophin-deficient mdx mouse. Our results indicate that high expression of the utrophin transgene in skeletal and diaphragm muscle can markedly reduce the dystrophic pathology. These data suggest that systemic upregulation of utrophin in DMD patients may lead to the development of an effective treatment for this devastating disorder.
杜兴氏肌肉营养不良症（DMD）是一种严重的进行性肌肉萎缩疾病，会导致心脏或呼吸衰竭，并在约20岁时导致死亡。在人类中使用成肌细胞移植或在小鼠DMD模型中使用病毒/脂质体递送方法来替代缺失的蛋白质——抗肌萎缩蛋白，效率低下且维持时间短。一种替代治疗方法是上调密切相关的蛋白质——抗肌萎缩蛋白聚糖，它或许能够补偿所有相关肌肉中抗肌萎缩蛋白的缺乏。作为该方法的第一步，我们已在缺乏抗肌萎缩蛋白的mdx小鼠中高水平表达了抗肌萎缩蛋白聚糖转基因。我们的结果表明，抗肌萎缩蛋白聚糖转基因在骨骼肌和膈肌中的高表达可显著减轻营养不良性病理变化。这些数据表明，在DMD患者中全身上调抗肌萎缩蛋白聚糖可能会促成针对这种毁灭性疾病的有效治疗方法的开发。
