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Inhibition of ASBT Improves Liver Function in an Animal Model of Cholestatic Liver Disease
Date:11/5/2013

SAN DIEGO, Nov. 5, 2013 /PRNewswire/ -- Lumena Pharmaceuticals, a company developing oral therapeutics for cholestatic liver diseases, today announced that inhibition of the apical sodium-dependent bile acid transporter (ASBT) improves liver function in animal models of cholestasis. The data will be presented at 11:15 a.m. EST today in an oral presentation titled "SC-435, an Oral Inhibitor of ASBT, Improves Liver Function in a Rat Partial Bile Duct Ligation Model of Cholestasis," at the 64th Annual Meeting of the American Association for the Study of Liver Diseases in Washington DC.

The study showed that inhibiting ASBT with SC-435, a close analog of LUM001, the company's lead drug candidate for the treatment of cholestatic liver disease, significantly improved markers of liver function in rats that had undergone partial bile duct ligation (pBDL) surgery to induce a state of cholestasis. Rats subjected to pBDL showed an impaired liver function as demonstrated by an increase in biomarkers of liver function, including serum liver alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and ɤ-glutamyl transferase (GGT) over baseline at three days post-surgery. Rats that received SC-435 showed an increase in excretion of bile acids in the feces, a reduction of serum bile acids and improvements in biomarker profiles of liver function at seven days post pBDL. The benefits of treatment with SC-435 were maintained at 14 days post pBDL, and histology studies showed that livers from rats treated with the ASBT inhibitor had less cell death and inflammatory cell infiltration. Taken together, the results show that inhibiting ASBT reduces circulating bile acid levels and improves liver function in animal models, suggesting that ASBT inhibition may be an attractive approach to treating cholestatic liver disease.


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SOURCE Lumena Pharmaceuticals
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