Descrizione del progetto
Nuovo farmaco genetico induce la rigenerazione cardiaca in seguito a infarto del miocardio
Le malattie cardiovascolari rappresentano la principale causa di morbilità e mortalità in tutto il mondo. Attualmente, tutti i farmaci disponibili per l’insufficienza cardiaca mirano a migliorare la funzionalità cardiaca residua, e nessuno affronta la perdita di cardiomiociti. Il progetto NICE, finanziato dall’UE, esplorerà nuovi approcci terapeutici. In precedenza il team ha identificato un microRNA umano capace di stimolare la proliferazione dei cardiomiociti; ora sintetizzerà chimicamente questo microRNA per poi formularlo in una nanoparticella lipidica (LNP199) completamente biocompatibile che protegge il microRNA dalla degradazione e promuove il rilascio intracellulare cardiaco, con l’obiettivo di indurre la rigenerazione cardiaca dopo un infarto del miocardio. NICE definirà la via ottimale per il rilascio di LNP199 confrontando tre diverse vie di somministrazione al cuore.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
Meccanismo di finanziamento
ERC-POC - Proof of Concept GrantIstituzione ospitante
WC2R 2LS London
Regno Unito