The exact cause of MS is unknown and molecular and cellular mechanisms of disease are still largely undefined, translating into our limited ability to prevent, cure or even effectively treat MS. Thus, the overarching goal of Epi4MS is not only to identify molecular causes of chronic inflammatory diseases such as MS but to go beyond by developing alternative modalities for precision medicine based on discovering and correcting modifiable aberrant epigenetic states. This will be achieved by our multifaceted approach, built on cutting-edge molecular and analytical tools, to study processes in affected human tissue followed by functional validation in experimental models, supported by the progress achieved thus far. Epi4MS will provide novel insights, already emerging from conducted studies, into the MS pathogenesis based on characterizing epigenetic states of pathogenic cells and focusing on the converging targets across multiple approaches to capture cellular MS culprits. This will significantly improve our understanding of disease pathogenesis as well as the mechanisms underlying the most potent MS drugs, opening up possibilities for further studies of pathogenic cells and importantly, provide candidates for new therapeutic interventions. Importantly, Epi4MS will develop strategies and tools to validate the functional impact of disease-associated epigenetic changes, in the form of emerging molecular tools, screens and in vivo models, thus uncovering regulatory states warranting further investigations. This facet will also provide valuable tools for high-throughput identification of methylation-sensitive regulatory elements, which will have applications in numerous conditions that associate with immune cell biology in general. Ultimately, Epi4MS will establish complementary approaches to functionally validate epigenetic changes and address their therapeutic potential in vivo, setting the stage for the development of alternative therapeutic modalities based on correcting aberrant epigenetic states.
