DIGNA BIOTECH

Amphiregulin

Amphiregulin (AR) is a member of the epidermal growth factor (EGF) family of proteins. AR is able to promote the growth and survival of different cell types, therefore representing an interesting molecule with potential applications in Regenerative Medicine. In mammals AR is expressed in different tissue types, albeit to a different extent. Our observations revealed that in the healthy liver parenchyma AR gene expression is almost undetectable. However this growth factor rapidly accumulates when the liver is injured in experimental models of tissue damage, as well as in human liver disease of viral or alcoholic etiology. Together these findings suggest that AR can participate in the natural regenerative response of the liver to injury, and that its controlled administration could enhance such reparative response.

The identification of hepatoprotective molecules is a highly relevant area of interest within biomedical research. Currently there are no available drugs that can effectively promote the survival and regeneration of liver parenchymal cells. Such lack of therapeutic resources is specially critical in situations of acute liver injury in which liver function may be compromised and result in acute liver failure (ALF). ALF is a dramatic patological condition with multiorganic complications including hepatic encephalopathy, brain edema, sepsis, respiratory and renal failure, intestinal bleeding and cardiovascular collapse. In spite of its low incidence, ALF remains a disease with a rapid evolution very high mortality (between 40 and 95% of the cases). ALF can be caused by a variety of agents that trigger liver injury such as hepatotropic viruses, drugs, toxins, metabolic alterations, acute ischemia and massive resection of the liver parenchyma. The successful management and resolution of ALF relies on the inhibition of hepatocellular damage and the regeneration of the lost parenchyma. Most of the therapeutic strategies available in the clinic are directed to the attenuation of the systemic complications of ALF. However there are no current strategies aimed at the prevention of hepatocyte necrosis and apoptosis or the stimulation of hepatocyte regeneration, leaving liver transplantation as the sole therapeutic alternative.

Parenteral administration of AR in experimental models that reproduce ALF of different etiology have demonstrated that this growth factor is a potent hepatoprotective agent. Our ongoing experiments are aimed to test the efficacy of AR in models of acute ischemia and reperfusion liver injury. This type of liver damage occurs during liver resection and organ transplantation, and in many cases limits the feasibility of the surgical intervention or compromises the viability of the graft. DIGNA Biotech is currently engaged in preclinical studies to assess the efficacy of AR in ischemia and reperfusion liver injury. Toxicological and pharmacokinetic studies will follow soon to pave the way towards phase I/II clinical trials.