Harish Pradeep, Forrest Leysa, Herath Shanti, Dickson George, Malerba Alberto, Popplewell Linda
Department of Biological Sciences, Centre of Gene and Cell Therapy and Biomedical Sciences, Royal Holloway, University of London, Egham, United Kingdom.
Front Physiol. 2020 Mar 5;11:184. doi: 10.3389/fphys.2020.00184. eCollection 2020.
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease presented by ptosis, dysphagia, and limb weakness. Affected muscles display increased fibrosis and atrophy, with characteristic inclusion bodies in the nucleus. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to improve symptoms in models of muscular dystrophy.
We systemically administered a monoclonal antibody to block myostatin in the A17 mouse model of OPMD at 42 weeks of age. The mice were administered a weekly dose of 10 mg/kg RK35 intraperitonially for 10 weeks, following which serum and histological analyses were performed on muscle samples.
The administration of the antibody resulted in a significant decrease in serum myostatin and collagen deposition in muscles. However, minimal effects on body mass, muscle mass and myofiber diameter, or the density of intranuclear inclusions (INIs) (a hallmark of disease progression of OPMD) were observed.
This study demonstrates that inhibition of myostatin does not revert muscle atrophy in a mouse model with established OPMD disease, but is effective at reducing observed histological markers of fibrosis in the treated muscles.
眼咽型肌营养不良症（OPMD）是一种迟发性肌肉疾病，表现为上睑下垂、吞咽困难和肢体无力。受影响的肌肉显示出纤维化和萎缩增加，细胞核中有特征性包涵体。肌生成抑制素是肌肉质量的负调节因子，在肌营养不良症模型中，抑制肌生成抑制素已被证明可改善症状。
我们在42周龄时，对OPMD的A17小鼠模型全身注射一种单克隆抗体以阻断肌生成抑制素。小鼠每周腹腔注射10 mg/kg RK35，持续10周，之后对肌肉样本进行血清和组织学分析。
抗体给药导致血清肌生成抑制素和肌肉中胶原蛋白沉积显著减少。然而，观察到对体重、肌肉质量和肌纤维直径，或核内包涵体（INIs）密度（OPMD疾病进展的标志）的影响极小。
本研究表明，在已建立OPMD疾病的小鼠模型中，抑制肌生成抑制素并不能恢复肌肉萎缩，但能有效减少治疗肌肉中观察到的纤维化组织学标志物。
