Descripción del proyecto
Un nuevo fármaco producido por técnica genética induce la regeneración cardíaca tras un infarto de miocardio
La enfermedad cardiovascular es la principal causa de morbimortalidad en el mundo. En la actualidad, todos los fármacos disponibles para la insuficiencia cardíaca tienen como objetivo mejorar el rendimiento cardíaco residual, pero ninguno aborda la pérdida de cardiomiocitos. El proyecto NICE, financiado con fondos europeos, estudiará nuevos métodos terapéuticos. Su equipo identificó previamente un microARN humano capaz de estimular la proliferación de cardiomiocitos; ahora sintetizará químicamente este microARN y lo formulará en una nanopartícula lipídica (LNP199) que es totalmente biocompatible, protege el microARN de la degradación y promueve su administración intracelular cardíaca, con el objetivo de inducir la regeneración cardíaca tras un infarto de miocardio. En NICE se determinará la ruta óptima para la administración de la LNP199 mediante una comparación de tres vías de administración al corazón diferentes.
Objetivo
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.
Ámbito científico
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Régimen de financiación
ERC-POC - Proof of Concept GrantInstitución de acogida
WC2R 2LS London
Reino Unido