Anti-MT Antibodies as Novel Therapy for Acetaminophen-Induced Liver Injury
Gut-Liver Immunopharmacology Unit
Project 1
Anti-MT Antibodies as Novel Therapy for Acetaminophen-Induced Liver Injury
Description
An overdose of acetaminophen (APAP), known as paracetamol, can cause severe liver damage and acute liver failure. Excessive intake of APAP exceeds normal metabolic pathways, results in glutathione depletion within hepatocytes and formation of cytotoxic protein adducts which lead to hepatocyte death and liver inflammation. To date, N-Acetylcysteine (NAC), a glutathione precursor, is the only pharmacological therapy. However, its efficacy decreases with increasing time between overdose and treatment and liver transplantation is the only life-saving option for patients that present too late. Thus, novel therapeutic options are an important medical need. Metallothioneins (MTs) have previously been identified as danger signals which are released from dying cells, attract other immune cells to the site of injury and sustain the inflammatory response. The pathogenesis of APAP-induced liver injury is critically influenced by the inflammatory response following hepatocyte death. Therefore, we believe that inhibiting MTs' danger signaling function by using anti-MT antibodies could deliver a novel therapeutic option for APAP overdosed patients. In this project, we will use human samples, a mouse model and in vitro assays to investigate the effect of anti-MT antibodies on APAP-induced liver damage in time, in combination with and in comparison to NAC.
Funding Ageny
FWO
Contact
Professor dr. Lindsey Devisscher