The failure of the liver 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. Hepatic injury by these agents frequently results in cell death. The liver has a remarkable ability to regenerate itself, but it sometimes sustains severe damage that cannot be reversed. The consequences of elevated cell death go beyond the simple loss of functional liver mass. Enhanced apoptosis may stimulate fibrogenesis, and increased cell turnover in the context of chronic inflammation may create a favourable scenario for cancer development. Thus, the identification of agents that reduce hepatocellular cell death is the special interest for the development of hepatoprotective therapeutics.

Cardiotrophin-1 (CT-1) belongs to the interleukin (IL-6) family of cytokines, which includes other cytokines such as IL-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M, IL-11, IL-27, cardiotrophin-like-cytokine (CLC) and neuropoietin. All cytokines in this family signal through receptor complexes that includes the receptor subunit glycoprotein-130 (gp-130).

It has been found that treatment with recombinant CT-1 is able not only to prevent Fas-induced apoptosis in various models of acute liver failure but can also reduce liver damage when given up to 3 hours after Fas-ligation, suggesting that CT-1 can block the apoptotic process when administered early after injury, a property that may increase its therapeutic potential.

Biotecnol and Digna Biotech, are developing recombinant human CT-1, exclusively in-licensed from Genentech, as a first in class drug to reduce ischemic reperfusion injury associated with organ transplantation and liver resection due to primary and secondary tumours, mainly originating from colorectal cancers. Both applications have a growing market with large unmet needs. CT-1 has already been granted Orphan Drug Status by the EMEA (Orphan Designation Number EU/3/06/396) for prevention of ischemia/reperfusion injury associated with solid organ transplantation, and a similar application has been granted by the FDA in June 2008.