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Novel Bile Acid Conjugates for the Treatment of NAFLD/NASH and Obesity

Tirosh Oren, HUJI, Faculty of Agricultural, Food and Environmental Quality Sciences, Biochemistry, Food Science and Nutrition
Madar Zecharia, HUJI, Faculty of Agricultural, Food and Environmental Quality Sciences, Biochemistry, Food Science and Nutrition
Sasson Shlomo, HUJI, School of Medicine - IMRIC, School of Pharmacy- Institute for Drug Research

Background

  • Fatty liver disease - Non alcoholic fatty liver disease (NAFLD) is  a continuum of diseases that include simple steatosis and non-alcoholic steatohepatitis (NASH) ultimately leading to cirrhosis, hepatocellular carcinoma (HCC) and/or end stage liver failure which develop in the absence of excessive alcohol intake.
  • NAFLD affects 30% of the general population and 70-80% of diabetic and obesity patients. Simple steatosis is most often considered to have a benign hepatic pathological prognosis. NASH, as oppose to steatosis is pathologically characterized by the presence of steatosis and inflammation, and is related to higher morbidity and mortality.
  • NASH is accounted for liver related complications, and it is one of the leading causes of liver transplantation.

 Our Innovation

  • A novel bile acid related small molecule that can be used to treat NAFLD and NASH. We have synthesized   an Arginine-bile acid conjugate (CDCArg) that was tested in animal nutritional models of NAFLD and obesity.
  • The compound is highly effective in preventing nutritional-induced NASH/NAFLD.
  • The compound is highly effective in treating nutrition-induced NASH/NAFLD.
  • The compound was effective in lowering body weight of obese high-fat diet fed mice.  

Key Features

  • A novel, orally administered, treatment for NAFLD and obesity.
  • Mechanism of action elucidated; Non-toxic.
  • Significantly lowering lipids absorption with no effect on protein absorption.

 

Patent Status

Granted US 9,884,066; China 2014800421992