Strategic study of atelocollagen-mediated application of myostatin-targeting siRNA for therapeutic use for muscular atrophy diseases

肌营养不良是一种严重的肌肉萎缩性疾病引起的基因突变。这种疾病是致命的，但基本的遗传缺陷的治疗方法尚未建立。近年来，针对肌营养不良症的有效治疗进行了大量研究，局部应用Mst-siRNA/ ATCOL复合物后，大鼠咬肌增大，而对侧未见明显变化。组织学分析显示，Mst-siRNA/ ATCOL复合物处理的咬肌的肌原纤维尺寸大于对照侧的那些。通过实时PCR分析进一步检查Mst-siRNA/ ATCOL处理的肌肉，显示在野生型和mCAV-3 Tg小鼠的处理的咬肌中Mst基因表达的显著下调。从肌电图记录，在mCAV-3 Tg小鼠咬肌活动量增加的Mst-siRNA/ ATCOL复合物的局部给药。此外，全身应用Mst-siRNA/ ATCOL复合物诱导mCAV-3 Tg小鼠TA肌肉的收缩力显著恢复。

Muscular dystrophy is a severe muscle wasting disorder caused by gene mutations. The disease is lethal, but the treatment of the basic genetic defect has not been established. Recently, many studies have been performed towards establishing an effective treatment for muscular dystrophy.After local application of the Mst-siRNA/ ATCOL complex, masseter muscles were enlarged, while no significant change was observed on the contralateral side. Histological analysis showed that the myofibril sizes of the masseter muscles treated with the Mst-siRNA/ ATCOL complex were larger than those of the control side. The Mst-siRNA/ ATCOL treated muscles were further examined by a real-time PCR analysis, showing a significant down-regulation of Mst gene expression in the treated masseters of both wild type and mCAV-3Tg mice. From EMG records, the amounts of masseter muscle activity in mCAV-3Tg mice were increased by local administration of Mst-siRNA/ ATCOL complex. Furthermore, systemic application of the Mst-siRNA/ ATCOL complex induced considerable recovery of contractile forces for TA muscles in mCAV-3Tg mice.