SBIR/STTR Award attributes
Abstract: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in children and adults associated with diet-associated hepatic lipid accumulation (steatosis), and is a common hepatic manifestation of obesity and metabolic syndromes including diabetes. Modulation Therapeutics is developing a stearoyl- coenzyme A desaturase-1 (SCD1) inhibitor for the treatment of NAFLD and NASH. The novel lead molecule referred to as MTI-301 is orally bioavailable and well-tolerated. Pilot data with MTI-301 in mice fed a Western high fat diet attenuated the liver steatosis and significantly improved liver function. We will leverage data generated in pre-clinical models of both a Western high fat diet as well as a Methionine-choline-deficient (MCD) diet to test the efficacy of MTI-301 as anti-steatosis single agent treatment option. In this proposal we will test our central hypothesis that sustained inhibition of SCD1 with the clinical lead molecule, MTI-301 as a single agent, will attenuate hepatic lipogenesis, reduce triglyceride accumulation, as well as reduce the liver injury, in diet-induced rodent models of NAFLD/NASH. To test our hypothesis in specific aim 1 we will utilize a well-established murine model of NAFDL and NASH and treat with different doses of MTI-301 In specific aim 2, we will evaluate the combination therapy of MTI-301 with pioglitazone, an anti-diabetic drug. Since obesity and metabolic syndromes contribute to the development of liver steatosis, we expect the combination to be reduce the liver dysfunction significantly. Prevention or reversal of liver steatosis is a significant therapeutic goal which can prevent multiple secondary metabolic disorders which increases morbidity and mortality worldwide.
