Project description
Glucose uptake restoration in diabetic and heart failure patients
Heart failure (HF) affects over 64 million people, with 40 % also having type 2 diabetes. Current HF treatments often ignore metabolic issues. A newly identified gene, more active in those with both conditions, HF and diabetes, influences glucose uptake. Reducing this gene’s expression improves glucose control and cardiac function in mice with heart failure on a high-fat diet. The ERC-funded CURE-HF project will develop safe, selective small molecules to inhibit this gene. It will validate promising compounds in both human iPSC-derived cardiomyocytes and diabetic HF mouse models. Targeting the energy deficit in diabetic HF could lead to therapies that reduce hospitalisations and enhance patient outcomes.
Objective
Heart failure (HF) affects over 64 million people worldwide and is a leading cause of hospitalization and premature death. About 40% of HF patients also have type 2 diabetes, doubling mortality risk. In HF, the stressed myocardium shifts toward glucose metabolism, but in diabetes cardiomyocytes fail to take up glucose and remain reliant on fatty acids, leaving the heart energy-starved. Current HF therapies target neurohormonal pathways to reduce workload and slow progression but do not address this root metabolic defect. Insulin and GLP-1 receptor agonists can influence glucose metabolism, but their use in HF is limited by side effects, lack of direct cardiac efficacy, or even potential harm.
CURE-HF proposes a novel approach by developing small-molecule inhibitors of a newly identified gene. Patient data revealed that this gene was the most differentially expressed in patients with heart failure and diabetes compared to heart failure patients without diabetes. Knockdown of this gene in hiPSC-derived cardiomyocytes increased glucose uptake, while mice lacking this gene on a high-fat diet with induced HF had better glucose control and 20% higher myocardial glucose uptake by FDG-PET and a better cardiac function. These findings demonstrate that inhibition of this gene restores energy balance and protects against diabetic HF.
Building on these insights, CURE-HF will design and optimise selective, safe, and synthetically accessible small molecules to inhibit the newly identified gene. Lead compounds will be validated in human iPSC-cardiomyocytes and in diabetic HF mouse models, with functional readouts including glucose uptake, echocardiography, and FDG-PET. In parallel, the project will secure IP, engage stakeholders, and assess market potential.
By addressing the root energetic deficit of diabetic HF, CURE-HF has the potential to deliver a disease-modifying small-molecule therapy, reduce hospitalization and improve prognosis.
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.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences health sciences nutrition
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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)
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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.
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-POC
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9713 GZ Groningen
Netherlands
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