Impact of Combined Baricitinib and FTI Treatment on Adipogenesis in Hutchinson-Gilford Progeria Syndrome and Other Lipodystrophic Laminopathies

The study investigates the effects of baricitinib (Bar) and its combination with farnesyltransferase inhibitor (FTI) on adipogenesis in Hutchinson-Gilford Progeria Syndrome (HGPS) and other lipodystrophic laminopathies, such as familial partial lipodystrophy type 2 (FPLD2) and mandibuloacral dysplasia type B (MADB). Using skin-derived precursor cells (SKPs) from human primary fibroblast cultures, the researchers found that Bar and Bar + FTI treatments significantly improved adipocyte differentiation and lipid droplet formation. Specifically, Bar and Bar + FTI increased differentiation rates and lipid droplet size in HGPS cells by 40% and 2-fold, respectively, and enhanced adipogenesis in FPLD2 and MADB cells by 86% and 41%, respectively. The findings suggest that Bar treatment alone enhances adipogenesis, and the combination with FTI may further ameliorate HGPS pathologies compared to lonafarnib alone.