MiRNAs as therapeutics for neurorepair in Multiple Sclerosis

Descripción del proyecto

Los microARN como herramienta para revertir la desmielinización en la esclerosis múltiple

La esclerosis múltiple (EM) es una enfermedad crónica del sistema nervioso central que se caracteriza por la desmielinización. Las terapias modificadoras de esta enfermedad disponibles son incapaces de inducir la neurorreparación e impedir el progresivo desarrollo de la discapacidad a partir de los daños neuronales. Se sabe que los microARN intervienen en la interacción genes-entorno que da lugar a la EM. El proyecto financiado con fondos europeos MiRepair tiene como objetivo identificar los microARN que intervienen en los procesos de desmielinización/remielinización y modular su expresión con el fin de promover la neurorreparación en la EM. La investigación combinará anteriores datos de microARN humanos con modelos experimentales robustos para identificar los microARN relacionados con la EM. El objetivo es utilizar matrices de hidrogel en combinación con moduladores de microARN para mejorar la remielinización en modelos animales «in vivo».

Objetivo

I hope to embark my first post-doctoral position, as a MSCA fellow, to identify microRNAs (miRNAs) involved in demyelination/remyelination processes with the final intention of modulating their expression as a therapeutic tool to promote neurorepair in multiple sclerosis (MS). MS is a chronic neurological disease of the central nervous system characterised by primary demyelination. All current disease-modifying therapies are unable to induce neurorepair and to prevent the progressive accumulation of disability from neuronal damage. miRNAs are one epigenetic mechanism involved in the genes-environment interaction that produces the pathology and symptoms in MS. My thesis project consists of describing miRNAs profiles in cerebrospinal fluid and serum of MS patients to exploit their potential role as clinical biomarkers. This project will combine these human miRNA data with robust experimental models in order to identify miRNAs involved in the damage and endogenous repair associated with MS. I will employ ex vivo models to study the biological role of miRNAs during these processes and how their manipulation might enhance neurorepair. The use of hydrogel-scaffolds in combination with miRNA modulators to enhance remyelination will be studied and preclinical MS in vivo models will be used to assess their therapeutic potential. I will work at the “microRNA Inflammation Group” in the Royal College of Surgeons in Ireland (RCSI) under mentorship of Dr Claire McCoy, a leader of MS research in Ireland. Two secondments have been planned in the National University of Ireland, Galway (NUIG) and Queen’s University Belfast (QUB). This fellowship will enable me to upskill in research techniques and expand my transferable skills and competences for a career path for academia or industry in miRNA therapeutics area. This will enhance and contribute to Europe’s competitiveness in R&I supporting European policy objectives as promoting excellence in education and skills development.