Hepatic fibrosis, a disease affecting tens of millions of patients worldwide, is the liver scarring response to chronic injury from viral hepatitis B or C, excessive alcohol use, iron overload or extrahepatic obstructions and can progress to liver cirrhosis, liver failure and death. In fact, deaths from complications of liver fibrosis/cirrhosis are expected to triple over the next decade as a result of the hepatitis C epidemic and the growing incidence of liver disease associated with non-alcoholic steatohepatitis. Currently available therapies, including antiviral, are largely ineffective in treating the underlying fibrosis, and in the majority of cases, liver transplantation is the only effective option. Scatter factor (SF), also known as hepatocyte growth factor (HGF), is a apheliotropic growth factor that induces the activation and proliferation of diverse cell types, largely through its mitogenic, motogenic and morphogenic activities. Additionally, SF/HGF exerts antifibrotic effects by modulating key profibrogenic elements including collagen and transforming growth factor-beta. In fact, several recently published studies have documented the therapeutic potential of exogenously administered SF/HGF in animal models of renal, pulmonary and liver fibrosis. A small molecule mimetic of SF/HGF has been discovered at Angion that recapitulates all in vitro and in vivo SF/HGF activities and has been shown to protect against liver fibrosis in two animal models. In order to further develop this promising compound as a potential therapeutic for fibrotic liver disease, it will be evaluated (1) in three animal models for its efficacy in liver fibrosis with respect to dose, time course of treatment, and route of administration, (2) in the studies of pharmacokinetics, toxicology and genotoxicity, (3) in the studies on its mechanism of action by proteomics. These studies are designed to collect complete data sets for the filing of an IND application. A safe and effective antifibrotic agent is expect to slow or stop the progression of liver fibrosis, prevent the development of end-stage liver cirrhosis, and possible reverse the pathological course of the diseases. ? ?
