Methods and compositions for modulating macrophages polarization

Inventors have surprisingly found that Emricasan is a much more potent inhibitor of monocyte differentiation compared to q-VD-OH by its ability to efficiently inhibit caspase-8, which is instrumental to this process. In addition, they have demonstrated that Emricasan alleviates the IL4-mediated M2-like polarization of human macrophages. Moreover, Emricasan also hampers bleomycin-induced pulmonary fibrosis in mice, a disease associated with an infiltration of M2-macrophages. Finally, caspase-8 deficient mice were found to be resistant to bleomycin-induced pulmonary fibrosis. As a whole, their findings indicate that the beneficial effect of Emricasan relies on its ability to inhibit caspase-8, and its capacity to prevent monocyte differentiation and M2 polarization of macrophages. Accordingly, the invention relates to a caspase 8 inhibitor for use in the polarization of macrophages.

Patent Application number: EP19306276.7
Reprogramming monocyte-derived macrophages through caspase inhibition Chantreuil P et al. OncoImunology 2022 VOL 11 issue 1 Article: 2015859

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