Project description
Targeted therapy for cardiac arrhythmia
Atrial fibrillation (AF), recognised as the most prevalent cardiac arrhythmia, frequently arises secondary to underlying structural heart abnormalities such as valvular disease or atrial enlargement. AF increases the risk of stroke and heart failure and can worsen over time due to adverse remodelling of heart tissue. Existing AF management strategies are invasive and cause significant side effects. The ERC-funded Chem-Afib project proposes a novel chemogenetic approach that uses harmless drugs to precisely silence arrhythmic cells which have been genetically modified to express synthetic receptors. The goal is to safely stop AF episodes without damaging the surrounding myocardial tissue. This innovative strategy could offer a safer and more targeted treatment for AF.
Objective
Atrial fibrillation (AF) is the most common sustained arrhythmia and is responsible for significant morbidity, mortality, and burden on the health care systems. Importantly, AF events may promote further fibrillatory episodes by inducing atrial remodelling. Traditional therapies for AF have relatively limited efficacy, and are either destructive (ablation), painful (defibrillation), or associated with side effects because of their global cardiac and systemic actions (drugs). Consequentially, novel treatment modalities for AF are direly needed.
Here, we propose to develop a targeted, functional, non-destructive, and easily administered treatment for AF termination that does not cause pain or other side effects, which can also potentially prevent the associated atrial remodelling.
Our proposed treatment is based on chemogenetics. This approach, which transformed neuroscience, utilizes inert drugs or designer molecules that have no effect on native host cells but can modulate the electrical properties of cells that are genetically modified to express specific chemogenetic receptors. Recently, we showed the feasibility of using chemogenetic tools for modulation of cardiac excitability. Here, we aim to evaluate the potential anti-arrhythmic capabilities of our newly created chemogenetic construct, which can cause transient electrical silencing in response to an inert drug. This approach has the potential to be the first chemogenetic tool capable of “defibrillating” cardiac tissue in a highly targeted manner. To evaluate the potential of this concept for treating AF, we plan to optimize its use and study its effects in an in vitro human cardiac tissue model of reentrant arrhythmias and in an in vivo AF rodent model.
The suggested approach represents a paradigm shift in the way AF can be treated and opens a pathway to targeting additional cardiac arrhythmias.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences clinical medicine cardiology cardiovascular diseases cardiac arrhythmia
- social sciences sociology demography mortality
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-POC
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32000 Haifa
Israel
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