New therapeutic approach for the treatment of cholemic nephropathy discovered

Cholaemic nephropathy is a serious kidney disease that occurs as a result of liver disease. There are no treatment options for the disease, as the mechanisms by which cholemic nephropathy is caused were previously unknown. The project groups of Prof. Ghallab and Prof. Hengstler at the Leibniz Institute for Occupational Research in Dortmund (IfADo) have now discovered the molecular cause of the disease and found a way to prevent the harmful effects that lead to kidney disease. These research findings could lead to new therapies to better help patients suffering from the disease.

Bile acids enter the kidney through a transport protein

The teams of Ghallab and Hengstler used a preclinical mouse model in which all known cholephiles increase in the blood, leading to cholemic nephropathy similar to that in humans. They discovered that the accumulation of bile acids occurs via a transport protein called SLC10A2 (also known as ASBT). By developing an inhibitor for this protein, they were able to successfully prevent the symptoms of cholemic nephropathy in a mouse model. An inhibitor is a substance that inhibits the activity of a specific protein or enzyme. As certain kidney cells in humans also produce the transport protein SLC10A2, the inhibitors used in mice have been optimized for use in humans and a clinical phase I study has already been completed. Blood tests on patients with cholemic nephropathy also showed similar disease-causing mechanisms as in the mouse model in which the original drug development took place. Together with their cooperation partners, the teams at IfADo are now planning a Phase II clinical trial to investigate the efficacy of this approach in patients.

The results and treatment options with SLC10A2 inhibitors were recently published in the Journal of Hepatology.