Description du projet
Un nouveau médicament génétique induit une régénération cardiaque après un infarctus du myocarde
Les maladies cardiovasculaires sont la principale cause de morbidité et de mortalité dans le monde. Actuellement, tous les médicaments disponibles pour l’insuffisance cardiaque visent à améliorer les performances cardiaques résiduelles, aucun ne traite la perte de cardiomyocytes. Le projet NICE, financé par l’UE, explorera de nouvelles approches thérapeutiques. L’équipe avait précédemment identifié un microARN humain capable de stimuler la prolifération de cardiomyocytes. Désormais, elle va synthétiser chimiquement ce microARN et le formuler en une nanoparticule lipidique (LNP199) entièrement biocompatible, protégeant le microARN de la dégradation et favorisant sa délivrance intracellulaire cardiaque, dans le but d’induire une régénération cardiaque après un infarctus du myocarde. NICE définira la voie optimale d’administration du LNP199 en comparant trois voies différentes d’administration au cœur.
Objectif
Prompt coronary catheterization and revascularization have dramatically improved the outcome of myocardial infarction, but also have resulted in a growing number of survived patients with permanent damage of the heart, which frequently leads to heart failure. This condition is now common, expensive and lethal. All currently available drugs for heart failure are aimed at improving residual cardiac performance, while none counteracts the loss of cardiomyocytes. We aim at developing an innovative biological drug that induces cardiac regeneration after myocardial infarction by stimulating endogenous cardiomyocyte proliferation. Our past work using high throughput screenings has identified a human microRNA (hsa-miR-199a-3p) that is effective at stimulating cardiomyocyte proliferation. Expression of this microRNA in the heart using an AAV vector leads to cardiac regeneration and improvement of cardiac function after myocardial infarction in both mice and pigs. A single administration of hsa-miR-199a-3p as a synthetic molecule is sufficient to stimulate cardiac repair. This project now aims at formulating this chemically synthetized miRNA into a lipid nanoparticle (LNP199) that is fully biocompatible, protects the miRNA from degradation and promotes its cardiac intracellular delivery. By experiments in large animals, the project will define the optimal route for LNP199 delivery by comparing three different routes of administration to the heart, any of which can be adopted for application according to standard clinical procedures. Delivery of LNP199 in pigs after ischemia reperfusion followed by cardiac MRI monitoring over time will provide information on the efficacy of this treatment in a clinically applicable scenario and highlight possible side effect. Among the advantages of this regenerative approach are one-off administration, relative ease of delivery according to standard interventional procedures, stability once manufactured and likely affordable cost.
Champ scientifique
Mots‑clés
Programme(s)
Régime de financement
ERC-POC - Proof of Concept GrantInstitution d’accueil
WC2R 2LS London
Royaume-Uni