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

    May 2023 in “ Cells
    Ramona Hartinger, Eva-Maria Lederer, Elisa Schena, Giovanna Lattanzi, Karima Djabali
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    Studysummary In this study, baricitinib treatment improved the differentiation of skin-derived precursors into adipocytes for diseases like Hutchinson-Gilford progeria syndrome, suggesting potential benefits when combined with lonafarnib. Our plain-language summary of this paper — not a Tressless recommendation.
    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.
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