Skip to main content
Przejdź do strony domowej Komisji Europejskiej (odnośnik otworzy się w nowym oknie)
polski pl
CORDIS - Wyniki badań wspieranych przez UE
CORDIS

Bioinspired Modulation of Cardiac Troponin I Splicing to Treat Diastolic Dysfunction

Cel

Diastolic dysfunction, i.e. impaired cardiac relaxation and filling, is a hallmark shared by various heart diseases, including hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF). It is often driven by excessive calcium sensitivity of the cardiac myofilaments, and in HCM and HFpEF alike, is associated with disrupted adrenergic signalling, culminating in reduced responsiveness of the heart to adrenaline. In the healthy heart, adrenergic stimulation normally decreases myofilament calcium sensitivity via phosphorylation of the N-terminus of cardiac troponin I (cTnI). Remarkably, this effect can also be mimicked by truncation of the cTnI N-terminus. We recently discovered that small mammals such as bats and shrews, which have extraordinarily high cardiac demands, have evolved to skip the exon encoding the cTnI N-terminus via alternative splicing or genomic deletion. This creates a permanently desensitized cTnI, bypassing the need for sustained β-adrenergic signalling. While alternative splicing of cTnI does not naturally occur in humans or most other mammals, it could be therapeutically induced using antisense oligonucleotides (AONs) in order to increase myocardial relaxation rate. TROPOSplice aims to develop a splice-switching antisense therapeutic that induces cTnI exon 3 skipping to mimic the myofilament desensitizing effect of adrenaline, leveraging a bioinspired strategy “from bats to bedside”. Crucially, as this approach acts downstream of adrenergic receptors, it is compatible with mainstay cardiovascular treatments such as beta-blockers. We will adopt a translational approach, from cultured cardiomyocytes to in vivo mouse models, to optimise AON design and delivery and to investigate the physiological effects of induced cTnI exon 3 skipping. This project offers a novel, evolution-guided therapeutic strategy to treat diastolic dysfunction and could ultimately benefit patients with HCM, HFpEF, and related heart conditions.

Dziedzina nauki (EuroSciVoc)

Projekt nie został jeszcze sklasyfikowany według klasyfikacji EuroSciVoc.
Wskaż dziedziny nauki, które twoim zdaniem są najbardziej istotne z punktu widzenia tego projektu i pomóż nam usprawnić naszą usługę klasyfikacji.

Słowa kluczowe

Program(-y)

Temat(-y)

System finansowania

HORIZON-ERC - HORIZON ERC Grants

Wyświetl wszystkie projekty finansowane w ramach tego programu finansowania

Zaproszenie do składania wniosków

(odnośnik otworzy się w nowym oknie) ERC-2026-STG

Wyświetl wszystkie projekty finansowane w ramach tego zaproszenia

Instytucja przyjmująca

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
Wkład UE netto
€ 1 499 625,00
Koszt całkowity
€ 1 499 625,00

Beneficjenci (1)