Grant: Project Grant

Patients suffering from cholestatic and autoimmune liver diseases accumulate toxic bile acid in their liver. We know that these toxic molecules are converted in non toxic glucuronide forms (aka BA-G) in the liver by detoxified in the liver by a series of enzymes called UGT. These non toxic forms are secreted into the intestine where enzymes called GUS from the intestinal bacteria can reactivate their toxic properties. Reactivated bile acids are reabsorbed in the intestine and go back to the liver. Non reactivated acids can be definitively eliminated in feces. We propose to identify a combination of drugs acting as UGT inducers and GUS inhibitors to promote the an efficient detoxification and elimination mechanism for bile acids in PBC and PSC patients.