Circulating miRNAs are generic and versatile therapeutic monitoring biomarkers in muscular dystrophies.
Circulating miRNAs are generic and versatile therapeutic monitoring biomarkers in muscular dystrophies.
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DOI：
10.1038/srep28097
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发表时间：
2016-06-21
影响因子：
4.6
通讯作者：
Richard I
中科院分区：
文献类型：
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作者：
Israeli D;Poupiot J;Amor F;Charton K;Lostal W;Jeanson-Leh L;Richard I
医学方法的发展需要临床前和临床试验来评估治疗效果。这种评估需要使用生物标志物，其提供关于对治疗干预的反应的信息。一类新提出的生物标志物是microRNA（miRNA）分子。在肌营养不良症（MD）中，最初在肌肉活检中观察到miRNA的失调，后来扩展到血浆样品，表明它们可能是感兴趣的生物标志物。首先，我们证明了肌营养不良蛋白相关糖蛋白复合物的表达被保留或被破坏的情况下，肌营养不良蛋白的失调发生在MD中，支持肌营养不良蛋白作为MD中的通用生物标志物的利用。然后，我们旨在评估miRNA作为监测MD实验性治疗方法的生物标志物的能力。为此，我们在α-肌聚糖病小鼠模型中利用了我们先前表征的基因治疗方法。我们确定了肌肉组织和血清中miRNA表达与治疗益处之间的剂量-反应相关性，如通过一组新的和经典使用的评估方法所评估的。本研究支持分析循环miRNA用于评价MD医学方法中的治疗结果的效用。
The development of medical approaches requires preclinical and clinical trials for assessment of therapeutic efficacy. Such evaluation entails the use of biomarkers, which provide information on the response to the therapeutic intervention. One newly-proposed class of biomarkers is the microRNA (miRNA) molecules. In muscular dystrophies (MD), the dysregulation of miRNAs was initially observed in muscle biopsy and later extended to plasma samples, suggesting that they may be of interest as biomarkers. First, we demonstrated that dystromiRs dysregulation occurs in MD with either preserved or disrupted expression of the dystrophin-associated glycoprotein complex, supporting the utilization of dystromiRs as generic biomarkers in MD. Then, we aimed at evaluation of the capacity of miRNAs as monitoring biomarkers for experimental therapeutic approach in MD. To this end, we took advantage of our previously characterized gene therapy approach in a mouse model for α-sarcoglycanopathy. We identified a dose-response correlation between the expression of miRNAs on both muscle tissue and blood serum and the therapeutic benefit as evaluated by a set of new and classically-used evaluation methods. This study supports the utility of profiling circulating miRNAs for the evaluation of therapeutic outcome in medical approaches for MD.