Albireo Lead Compound A4250 Shows Promise Against Liver Injury In Mice
Swedish biotechnology company Albireo announced that its lead compound A4250 for cholestatic liver disease was successful in protecting against bile acid-mediated cholestatic liver damage in mice.
A4250 belongs to the ileal bile acid transporter (IBAT) class of inhibitors and is a molecule with the capacity to be a total inhibitor of the IBAT with minimal systemic exposure. In the study, A4250 decreased key cholestatic liver disease biomarkers such as ALT, ALP and serum bile acids. The compound also reduced portal inflammation and reduced pro-inflammatory biomarkers such as TNF-α, Mcp-1 and Vcam-1, in line with initial findings.
The data was orally presented as “Inhibition of Intestinal Bile Acid Absorption by ASBT Inhibitor A4250 Protects Against Bile Acid-Mediated Cholestatic Liver Injury In Mice” at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL) held in London, UK.
Hans Graffner, CMO at Albireo, said, “The data in this trial clearly indicate that A4250 has beneficial effects on a broad range of biochemical liver function parameters and A4250 has potential as a novel hepatoprotective drug that may help preserve liver function in a number of chronic liver diseases such as PBC (primary biliary cirrhosis) and PSC (primary sclerosing cholangitis)”.
A4250 decreases the re-absorption of bile acids and helps reduce the toxic levels of bile acids in the liver cells. The company believes that given the mode of action of A4250, it should also be advantageous in liver diseases due to metabolic disturbances such as NASH (nonalcoholic steatohepatitis).
The study was conducted in a well-established animal model of cholestatic liver injury at the laboratory of Professor Michael Trauner of Medical University in Vienna, Austria. Further studies for A4250 in disease areas such as PBC, PSC and hereditary causes of cholestasis (such as progressive familial intrahepatic cholestasis) are currently in the planning stages.