Targeting Acid Ceramidase to Reverse NASH Fibrosis
2021 Harrington Scholar-Innovator
Approximately 30 million Americans have nonalcoholic steatohepatitis (NASH), a chronic inflammation of the liver that can lead to serious damage in the form of scarring (cirrhosis) or liver cancer. There are no FDA-approved therapies for its treatment.
Dr. Jennifer Chen and her colleagues at UCSF have identified a novel antifibrotic target: acid ceramidase (aCDase). In preclinical studies, deletion or inhibition of aCDase leads to inactivation of hepatic stellate cells (HSCs), the primary cell type responsible for hepatic fibrosis. In mouse models, deleting aCDase in HSCs reduces fibrosis development and promotes fibrosis regression. Treatment with an aCDase inhibitor also promotes fibrotic regression in cirrhotic human liver tissue ex vivo.
“While doing my clinical work I was struck by how many of my patients had end-stage liver disease—particularly NASH,” Dr. Chen says. “Many didn't know they had it, and there were no treatment options for them. As a physician-scientist trained in hepatology, I am passionate about identifying new targets and potentially developing therapies for these patients.”
Working toward the goal of creating a first-in-class small molecule aCDase inhibitor, Dr. Chen and her colleagues are performing lead series optimization and confirming the efficacy of developmental compounds using in-vivo and ex-vivo models of NASH. Ensuring that the compounds can be made orally available is a major focus.
Dr. Chen says she is impressed by how collaborative the process has been with the Harrington team.
“We've developed so many great partnerships,” she says. “I think that really highlights how important it is to understand fibrotic diseases and develop new therapies, because there is such a huge unmet need.”
Dr. Jennifer Chen's NASH Breakthrough - Reversing Liver Fibrosis. Dr. Jennifer Chen, University of California, San Francisco, Harrington Scholar, is working towards creating a novel therapy for nonalcoholic steatohepatitis (NASH), a chronic inflammation of the liver that can lead to serious damage in the form of scarring (cirrhosis) or liver cancer. Dive into the world of nonalcoholic steatohepatitis (NASH) and discover the potential game-changer, acid ceramidase (aCDase). Chen explains a future with effective NASH treatments, making a difference in the lives of millions.