Abstract：
Myostatin is a member of the transforming growth factor-beta superfamily and is an endogenous negative regulator of muscle growth. This study aimed to determine whether an oral administration of Lactobacillus casei expressing modified human myostatin (BLS-M22) could elicit sufficient levels of myostatin-specific antibody and improve the dystrophic features of an animal model of Duchenne muscular dystrophy (DMD; mdx mouse). BLS-M22 is a recombinant L. casei engineered to harbor the pKV vector and poly-gamma-glutamic acid gene linked to a modified human myostatin gene. Serological analysis showed that anti-myostatin IgG titers were significantly increased, and serum creatine kinase was significantly reduced in the BLS-M22-treated mdx mice compared to the control mice. In addition, treatment of BLS-M22 resulted in a significant increase in body weight and motor function (Rotarod behavior test). Histological analysis showed an improvement in the dystrophic features (fibrosis and muscle hypertrophy) of the mdx mice with the administration of BLS-M22. The circulating antibodies generated after BLS-M22 oral administration successfully lowered serum myostatin concentration. Myostatin blockade resulted in serological, histological, and functional improvements in mdx mice. Overall, the findings suggest the potential of BLS-M22 to treat DMD; however, further clinical trials are essential to ascertain its efficacy and safety in humans.
摘要：
肌肉生长抑制素是转化生长因子-β超家族的成员,并且是肌肉生长的内源性负调节因子。本研究旨在确定口服施用表达修饰的人类肌肉生长抑制素(BLS-M22)的干酪乳杆菌是否可以引起足够水平的肌肉生长抑制素特异性抗体并改善杜氏肌营养不良(DMD;mdx小鼠)动物模型的营养不良特征。BLS-M22是重组干酪乳杆菌,其被工程化以携带pKV载体和与修饰的人肌肉生长抑制素基因连接的聚-γ-谷氨酸基因。血清学分析显示抗肌生成抑制素IgG滴度显著升高,与对照小鼠相比，BLS-M22治疗的mdx小鼠的血清肌酸激酶显着降低。此外,BLS-M22的治疗导致体重和运动功能的显着增加（旋转杆行为测试）。组织学分析显示,施用BLS-M22后,mdx小鼠的营养不良特征(纤维化和肌肉肥大)得到改善。口服BLS-M22后产生的循环抗体成功地降低了血清肌肉生长抑制素浓度。肌肉生长抑制素阻断导致血清学，组织学,和mdx小鼠的功能改善。总的来说,研究结果表明，BLS-M22治疗DMD的潜力;然而，进一步的临床试验对于确定其在人体中的有效性和安全性至关重要。
