Descripción del proyecto
Tratamientos epigenéticos para la esclerosis múltiple
La esclerosis múltiple (EM, o MS por sus siglas en inglés) es una enfermedad autoinmunitaria progresiva cuya causa se desconoce. El proyecto financiado con fondos europeos Epi4MS trabaja con la hipótesis de que la EM aparece debido a cambios epigenéticos, que afectan a la expresión génica pero no al código genético «per se». Sus investigadores definirán y vincularán estados epigenéticos con la patogenia de la EM y evaluarán el potencial terapéutico de la edición del epigenoma en modelos murinos de la enfermedad. Los resultados ayudarán a determinar los mecanismos moleculares subyacentes de la EM y posibilitarán el desarrollo de tratamientos innovadores. Es más, sentarán las bases para revertir estados epigenéticos anómalos en otras enfermedades agresivas de origen inmunitario.
Objetivo
Multiple Sclerosis (MS) is a leading cause of unpredictable and incurable progressive disability in young adults. Although the exact cause remains unknown, this immune-mediated disease is likely triggered by environmental factors in genetically predisposed individuals. I propose that epigenetic mechanisms, which regulate gene expression without affecting the genetic code, mediate the processes that cause MS and that aberrant epigenetic states can be corrected, spearheading the development of alternative therapies. We will exploit the stable and reversible nature of epigenetic marks, in particular DNA methylation, to gain insights into the novel modifiable disease mechanisms by studying the target organ in a way that has not been possible before. This highly ambitious project comprises three synergistic facets formulated in specific aims to: (i) identify epigenetic states that characterize the pathogenesis of MS, (ii) prioritize functional epigenetic states using high-throughput epigenome-screens, and (iii) develop novel approaches for precision medicine based on correcting causal epigenetic states. Our unique MS biobank combined with cutting-edge methodologies to capture pathogenic cells and measure their functional states provides a rational starting point to identify MS targets. I will complement this approach with studies of the functional impact of MS targets using innovative in vitro screens, with the added value of unbiased discovery of robust regulators of specific MS pathways. Finally, my laboratory has extensive experience with animal models of MS and I will utilize these powerful systems to dissect molecular mechanisms of MS targets and test the therapeutic potential of targeted epigenome editing in vivo. Our findings will set the stage for a paradigm-shift in studying and treating chronic inflammatory diseases based on preventing and modulating aggressive immune responses by inducing self-sustained reversal of aberrant epigenetic states.
Ámbito científico (EuroSciVoc)
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.
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Palabras clave
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
17177 Stockholm
Suecia