Hepatocyte Growth Factor Mimetic for Liver Fibrosis

DESCRIPTION (provided by applicant): Hepatic fibrosis, a disease affecting tens of millions of patients worldwide, is the liver scarring response that occurs in response to chronic injury from viral hepatitis B or C, excessive alcohol use, and iron overload, and often leads to liver failure and death. Despite the availability of antiviral and other therapies, most are ineffective in treating the underlying fibrosis and are associated with many side effects. Death from complications of liver fibrosis is expected to triple over the next decade as a result of the hepatitis C (HCV) epidemic and growing incidence of liver disease associated with obesity, so-called "non-alcoholic steatohepatitis" (NASH). Increasing numbers of patients are presenting to tertiary care centers in need of liver transplantation. Unfortunately, the number of cadaveric organs available for transplantation has plateaued and living related donor transplants have not shortened waiting lists. Hence, there is a critical need for potent antifibrotic therapies. Several recently published studies have demonstrated the therapeutic potential of exogenously administered HGF in the treatment of animal models of liver fibrosis. Endogenous HGF plays a key role in inhibiting fibrogenesis at least in part by downregulating TGFb1, the most potent factor for fibrogenesis. It may also act by its proliferative and anti-apoptotic actions. While administration of HGF holds promise as a therapeutic avenue for the treatment of liver fibrosis, protein-based therapies are notoriously difficult to administer because of potential immune responses, instability in solution, and cost-prohibitive production schemes. To overcome these shortfalls, low molecular weight compounds that mimic the activity of HGF would provide substantially improved therapeutic potential. Angion Biomedica Corp. has identified C6, a small molecular weight compound that mimics the effects of HGF both in vitro and in vivo. C6 inhibits renal cell apoptosis, promotes angiogenesis, prevents increased creatinine by renal ischemia and decreases the incidence of tubular necrosis in the mercuric chloride model of kidney failure. It is likely that C6 will have an antifibrotic effect in an animal model of liver fibrosis. These studies will provide the basis for more extensive Phase II studies to bring this potential therapy into clinical trials.