Project description
New genetic drug induces cardiac regeneration after myocardial infarction
Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Currently, all available drugs for heart failure aim at improving residual cardiac performance, and none address the loss of cardiomyocytes. The EU-funded NICE project will explore new therapeutic approaches. The team previously identified a human microRNA capable of stimulating cardiomyocyte proliferation; now it will chemically synthesise this microRNA and formulate it into a lipid nanoparticle (LNP199) that is fully biocompatible, protects the microRNA from degradation and promotes its cardiac intracellular delivery, with the aim to induce cardiac regeneration after myocardial infarction. NICE will define the optimal route for LNP199 delivery by comparing three different routes of administration to the heart.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
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Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
WC2R 2LS London
United Kingdom