Descrizione del progetto
Un trattamento basato sull’RNA per l’insufficienza cardiaca
L’insufficienza cardiaca è correlata alla fibrosi cardiaca, o cicatrizzazione, una conseguenza inevitabile di un insulto miocardico che colpisce la funzione diastolica e sistolica. Nonostante il suo grande peso socioeconomico, non esistono trattamenti per ripristinare la fibrosi cardiaca e curare l’insufficienza cardiaca. Il progetto MEGFIB, finanziato dall’UE, propone di sviluppare un nuovo approccio per trattare pazienti con insufficienza cardiaca selezionati sulla base di RNA non codificanti, che si stanno rivelando elementi importanti nella patogenesi della malattia. Gli scienziati, utilizzando oligonucleotidi indirizzati all’RNA lungo meg3 non codificante nelle cellule e nei tessuti umani, si augurano di replicare i risultati ottenuti nei modelli animali e di stabilire un nuovo approccio nel trattamento dell’insufficienza cardiaca.
Obiettivo
Cardiac fibrosis is a hallmark of and mechanistically involved in heart failure; a disease will high clinical unmet need and fundamental socioeconomic importance. Specific treatments of cardiac fibrosis are lacking. RNAs that do not code for proteins comprise a large portion of the human genome. These so-called noncoding RNAs are emerging as important players in disease pathogenesis, yet their functional roles are ill understood. Our group currently pioneered first clinical testings on noncoding RNA inhibitors in heart failure patients showing the enormous clinical translational potential of such next-generation therapeutics. We now aim to develop a new approach to treat selected heart failure patients, which show increased signs of cardiac fibrosis. Within the ERC grant LONGHEART we have identified a lncRNA meg3 to be a novel and innovative target in heart failure pathologies with fibrosis (Circ Res. 2017 Aug 18;121(5):575-583; Fig. 1). Importantly meg3 is well conserved between rodents and humans allowing translational development. Oligonucleotide-mediated silencing of Meg3 in human cardiac fibroblasts and in vivo in mice resulted in decreased cardiac fibrosis and improved diastolic performance of the heart. Within MEGFIB, we now aim to advance these valuable research results on meg3-based improvements of cardiac fibrosis in mice towards commercial proof-of-concept. Important next steps are a) translation of the efficacy to human cells and tissues and b) sophisticated market analysis, c) IP strategy development and d) business development activities to maximize the value of the projects’ results. The outcome of our activities will be consolidated into a business plan for presenting our proposition to strategic partners, such as Cardior Pharmaceuticals or venture capitalists (VCs). We are proposing a unique RNA-based approach that offers a new opportunity to revolutionize medical practice, improve patient care and will reduce costs in the heart failure care.
Campo scientifico
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Meccanismo di finanziamento
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotIstituzione ospitante
30625 Hannover
Germania