DIGNA BIOTECH

Cardiotrophin-1

Acute liver failure is caused by a variety of insults, including toxic liver damage by poisons or drugs, immune or viral hepatitis, ischemia/reperfusion injury and graft rejection.

The liver has a remarkable ability to regenerate itself, but he may be overcome in situations of acute damage. Therefore, the identification of agents that reduce hepatocellular death has a special interest in the development of hepatoprotective therapeutics.

Cardiotrophin-1 (CT-1) belongs to the Interleukin-6 cytokine family. Our studies have shown that CT-1 is expressed in the liver, mainly by parenchymal cells. Binding of CT-1 to its receptor on hepatocytes triggers the activation of cell survival pathways: STAT-3, AKT and ERK1/2.

The administration of recombinant CT-1 has shown a clear hepatoprotective effect in several animal models of liver failure, such as the mice model of concanavalin-A induced hepatitis, the Fas-induced apoptosis in rodents and the fulminant viral hepatitis rabbit model.

CT-1 has also demonstrated its ability to induce liver regeneration in partial hepatectomy models. Its action was studied in a model of 70% hepatectomy in mini-pig resulting in an induction in liver regeneration and a decrease in the levels of liver damage markers. In a more extensive hepatectomy model in rat, we have managed to reproduce the same effect.

Digna Biotech, together with Biotecnol, is developing recombinant human CT-1 as a first in class drug to reduce ischemic reperfusion injury in the liver or kidney transplantation field and liver regeneration following hepatectomy. CT-1 has already been granted Orphan Drug Status by the EMEA (Orphan Designation Number EU/3/06/396) and the FDA for prevention of ischemia/reperfusion injury associated with solid organ transplantation.

Currently, the documentation for other CT-1 applications has been submitted in order to be evaluated by the regulatory agencies.