Therapeutics: Cyclin dependent kinase 4 (CDK4); CCAAT enhancer binding protein α (CEBPA)

Patient sample and mouse studies suggest CDK4 inhibitors could help treat non-alcoholic fatty liver disease (NAFLD). In patient liver tissue samples, CDK4 levels were higher than in samples from healthy volunteers. In a mouse model of NAFLD, expression of a CDK4-resistant mutant of the CDK4 substrate CEBPA decreased hepatic steatosis and liver fibrosis compared with expression of wild-type CEBPA. Also in the model, the CDK4/CDK6 inhibitor Ibrance palbociclib decreased markers of hepatic steatosis compared with vehicle. Next steps include testing CDK4 inhibitors to treat liver fibrosis and non-alcoholic steatohepatitis (NASH) in patients with late-stage NAFLD...