Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
BioMarin Nederland BV, Leiden, The Netherlands.
Sci Rep. 2021 Mar 15;11(1):5952. doi: 10.1038/s41598-021-84863-w.
Becker muscular dystrophy (BMD) is the milder allelic variant of Duchenne muscular dystrophy, with higher dystrophin levels. To anticipate on results of interventions targeting dystrophin expression it is important to know the natural variation of dystrophin expression between different muscles and over time. Dystrophin was quantified using capillary Western immunoassay (Wes) in the anterior tibial (TA) muscle of 37 BMD patients. Variability was studied using two samples from the same TA biopsy site in nine patients, assessing nine longitudinal TA biopsies, and eight simultaneously obtained vastus lateralis (VL) muscle biopsies. Measurements were performed in duplicate with two primary antibodies. Baseline dystrophin levels were correlated to longitudinal muscle strength and functional outcomes. Results showed low technical variability and high precision for both antibodies. Dystrophin TA levels ranged from 4.8 to 97.7%, remained stable over a 3-5 year period, and did not correlate with changes in longitudinal muscle function. Dystrophin levels were comparable between TA and VL muscles. Intra-muscle biopsy variability was low (5.2% and 11.4% of the total variability of the two antibodies). These observations are relevant for the design of clinical trials targeting dystrophin production, and may urge the need for other biomarkers or surrogate endpoints.
贝克肌营养不良症（BMD）是杜氏肌营养不良症的轻度等位基因变异，其肌营养不良蛋白水平较高。为了预测针对肌营养不良蛋白表达的干预措施的结果，了解不同肌肉之间以及随时间推移肌营养不良蛋白表达的自然变化非常重要。使用毛细管 Western 免疫分析（Wes）在 37 名 BMD 患者的胫骨前肌（TA）中定量肌营养不良蛋白。在 9 名患者中使用来自同一 TA 活检部位的两个样本研究了变异性，评估了 9 个纵向 TA 活检和 8 个同时获得的股外侧肌（VL）肌肉活检。使用两种主要抗体进行了两次重复测量。基线肌营养不良蛋白水平与纵向肌肉力量和功能结果相关。结果表明，两种抗体的技术变异性低且精度高。TA 肌营养不良蛋白水平范围为 4.8%至 97.7%，在 3-5 年内保持稳定，与纵向肌肉功能的变化无关。TA 和 VL 肌肉中的肌营养不良蛋白水平相当。肌肉内活检变异性较低（两种抗体总变异性的 5.2%和 11.4%）。这些观察结果与针对肌营养不良蛋白产生的临床试验设计相关，可能需要其他生物标志物或替代终点。
