One of the first targets proposed as an anti-fibrotic therapy was CCN2. Proof of its involvement in fibrosis was initially difficult, due to the lack of appropriate reagents and general understanding of the molecular mechanisms responsible for persistent fibrosis. As these issues have been progressively resolved over the last twenty-five years, it has become clear that CCN2 is a bone fide target for anti-fibrotic intervention. An anti-CCN2 antibody (FG-3019) is in Phase III clinical trials for idiopathic pulmonary fibrosis and pancreatic cancer, and in Phase II for Duschenne's muscular dystrophy. An exciting paper recently published by Mary Barbe and the Popoff group has shown that FG-3019 reduces established muscle fibrosis (Barbe et al., FASEB J 34:6554-6569, 2020). Intriguingly, FG-3019 blocked the decreased expression of the anti-fibrotic protein CCN3, caused by the injury model. These important data support the notion that targeting CCN2 in the fibrotic microenvironment may reverse established fibrosis, making it the first agent currently in development to do so.

中文翻译：

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慢速驶来：抗CCN2策略逆转了慢性过度使用肌肉纤维化的模型。

提出作为抗纤维化疗法的首批靶标之一是CCN2。由于缺乏合适的试剂以及对引起持续性纤维化的分子机制的一般理解，最初难以证明其参与纤维化。随着这些问题在过去的25年中逐步得到解决，很明显CCN2是抗纤维化干预的真正目标。抗CCN2抗体（FG-3019）处于特发性肺纤维化和胰腺癌的III期临床试验中，而Duschenne的肌营养不良症则处于II期中。Mary Barbe和Popoff小组最近发表的一篇令人振奋的论文表明，FG-3019可以减轻既定的肌肉纤维化（Barbe等人，FASEB J 34：6554-6569，2020）。有趣的是 FG-3019阻止了由损伤模型引起的抗纤维化蛋白CCN3表达的降低。这些重要的数据支持这样的观念，即在纤维化微环境中靶向CCN2可能逆转已建立的纤维化，使其成为目前正在开发的第一个这样做的药物。