Recently, several promising treatments have emerged for neuromuscular disorders, highlighting the need for robust biomarkers for monitoring therapeutic efficacy and maintenance of the therapeutic effect. Several studies have proposed circulating and tissue biomarkers, but none of them has been validated to monitor acute and long-term drug response. We previously described how the myostatin (MSTN) level is naturally downregulated in several neuromuscular diseases, including Duchenne muscular dystrophy (DMD). Here, we show that the dystrophin-deficient Golden Retriever muscular dystrophy (GRMD) dog model also presents an intrinsic loss of Mstn production in muscle. The abnormally low levels of Mstn observed in the GRMD dog puppies at 2 months were partially rescued at both mRNA and protein level after adeno-associated virus (AAV)-microdystrophin treatment in a dose-dependent manner. These results show that circulating Mstn is a robust and reliable quantitative biomarker, capable of measuring a therapeutic response to pharmaco-gene therapy in real time in the neuromuscular system, as well as a quantitative means for non-invasive follow-up of a therapeutic effect. Moreover, a 2-year follow-up also suggests that Mstn could be a longitudinal monitoring tool to follow maintenance or decrease of the therapeutic effect.

近来，已经出现了几种针对神经肌肉疾病的有前途的治疗方法，突显了对用于监测治疗效果和维持治疗效果的健壮生物标志物的需求。几项研究提出了循环和组织生物标志物，但没有一项可以用于监测急性和长期药物反应。先前我们描述了肌生成抑制素（MSTN）水平在包括杜氏肌营养不良症（DMD）在内的几种神经肌肉疾病中是如何自然下调的。在这里，我们显示了肌营养不良蛋白缺陷型金毛寻回犬肌肉营养不良（GRMD）狗模型还呈现出肌肉中Mstn产生的固有损失。在腺相关病毒（AAV）-微肌营养不良蛋白以剂量依赖的方式治疗后，在2个月的GRMD狗幼犬中观察到的异常低水平的Mstn在mRNA和蛋白质水平上得到部分挽救。这些结果表明，循环Mstn是一种可靠且可靠的定量生物标志物，能够实时测量神经肌肉系统中对药物基因疗法的治疗反应，以及用于无创随访治疗效果的定量手段。此外，为期2年的随访还表明，Mstn可能是纵向监测工具，可以跟踪维持或降低治疗效果。能够实时测量神经肌肉系统中对药物基因治疗的治疗反应，以及用于无创随访治疗效果的定量方法。此外，为期2年的随访还表明，Mstn可能是纵向监测工具，可以跟踪维持或降低治疗效果。能够实时测量神经肌肉系统中对药物基因治疗的治疗反应，以及用于无创随访治疗效果的定量方法。此外，为期2年的随访还表明，Mstn可能是纵向监测工具，可以跟踪维持或降低治疗效果。