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.