The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC, USA; Pediatrics, Epidemiology and Biostatistics, George Washington University, Washington, DC, USA.
Neuromuscul Disord. 2023 Feb;33(2):199-207. doi: 10.1016/j.nmd.2023.01.001. Epub 2023 Jan 6.
Myostatin is a myokine which acts upon skeletal muscle to inhibit growth and regeneration. Myostatin is endogenously antagonised by follistatin. This study assessed serum myostatin and follistatin concentrations as monitoring or prognostic biomarkers in dysferlinopathy, an autosomal recessively inherited muscular dystrophy. Myostatin was quantified twice with a three-year interval in 76 patients with dysferlinopathy and 38 controls. Follistatin was quantified in 62 of these patients at the same timepoints, and in 31 controls. Correlations with motor function, muscle fat fraction and contractile cross-sectional area were performed. A regression model was used to account for confounding variables. Baseline myostatin, but not follistatin, correlated with baseline function and MRI measures. However, in individual patients, three-year change in myostatin did not correlate with functional or MRI changes. Linear modelling demonstrated that function, serum creatine kinase and C-reactive protein, but not age, were independently related to myostatin concentration. Baseline myostatin concentration predicted loss of ambulation but not rate of change of functional or MRI measures, even when relative inhibition with follistatin was considered. With adjustment for extra-muscular causes of variation, myostatin could form a surrogate measure of functional ability or muscle mass, however myostatin inhibition does not form a promising treatment target in dysferlinopathy.
肌肉生长抑制素是一种肌因子，作用于骨骼肌以抑制生长和再生。肌肉生长抑制素被卵泡抑素内源性拮抗。本研究评估了血清肌肉生长抑制素和卵泡抑素浓度作为肌营养不良症（一种常染色体隐性遗传性肌肉疾病）的监测或预后生物标志物。在 76 名肌营养不良症患者和 38 名对照者中，每隔三年对肌肉生长抑制素进行了两次定量检测。在同一时间点对 62 名患者和 31 名对照者进行了卵泡抑素的定量检测。进行了与运动功能、肌肉脂肪分数和收缩横截面积的相关性分析。使用回归模型来解释混杂变量。基线肌肉生长抑制素，但不是卵泡抑素，与基线功能和 MRI 测量相关。然而，在个别患者中，肌肉生长抑制素的三年变化与功能或 MRI 变化无关。线性模型表明，功能、血清肌酸激酶和 C 反应蛋白，而不是年龄，与肌肉生长抑制素浓度独立相关。基线肌肉生长抑制素浓度预测丧失步行能力，但不能预测功能或 MRI 测量的变化率，即使考虑了卵泡抑素的相对抑制作用也是如此。在调整肌肉外因素引起的变化后，肌肉生长抑制素可以作为功能能力或肌肉质量的替代测量指标，但是肌肉生长抑制素抑制在肌营养不良症中并不是一个有前途的治疗靶点。
