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Next Generation Gene Therapy for the Treatment of Chronic Myocardial Ischemia and Heart Failure

Project description

VEGF-based gene therapy for the treatment of chronic heart conditions

Vascular endothelial growth factors (VEGFs) are signaling proteins produced by cells and involved in the creation of new blood vessels during embryonic development or after injury, and of new bypasses (collateral circulation) to blocked vessels. The EU-funded HeartGenes project will develop novel VEGF-B and VEGF-C-based gene therapy to treat refractory angina and heart failure (HF), using exogenous gene transfer and new endogenous gene activation technology. VEGF-B and VEGF-C factors were selected as lead targets from extensive pig studies, where they showed the best benefits among all VEGFs, such as relative cardiac specificity, potent angiogenic and metabolic effects (VEGF-B) and lymphangiogenic activity (VEGF-C).

Objective

BACKGROUND: Therapeutic angiogenesis has great potential for the treatment of severe heart diseases. However, this requires novel approaches and development of new technology.

ADVANCING STATE-OF-THE-ART: We will develop novel VEGF-B and VEGF-C-based gene therapy to treat refractory angina and heart failure (HF). VEGF-B and VEGF-C lead factors were selected from extensive pig studies where they showed the best benefits among all VEGFs, such as relative cardiac specificity, potent angiogenic and metabolic effects (VEGF-B) and lymphangiogenic activity (VEGF-C). Exogenous gene transfer and new endogenous gene activation technology will be developed.

Key new technologies are riboswitch-regulated-AAV8 vectors, Super-Enhancer driven cell-type targeted gene expression, VEGF-B and VEGF-C designer mutants for better efficacy and activation of natural endogenous VEGF-B and VEGF-C expression with promoter binding shRNAs, circRNAs, CRISPR/mutantCas9-VP64-SAM gene activation technology and using a novel concept of the release of promoter pausing. Immunological concerns of AAV8 and usefulness of new synthetic dendrimer carriers will be addressed.

HeartGenes utilizes optimized percutaneous intramyocardial and retrograde venous gene delivery in pig chronic ischemia and HF models, clinically relevant pig exercise test, and 15O-H2O and 18F-FDG PET/MRI imaging to detect treatment effects.

Simultaneously, HeartGenes will take a realistic approach to clinical translation and starts intramyocardial vs retrograde venous riboswitch-AAV8-VEGF-B186 phase I trial in refractory angina as the first step to bring the best novel constructs and the most advanced functional and imaging endpoints developed in HeartGenes to clinical testing at the end of the project.

SIGNIFICANCE: If successful, this approach will bring a paradigm shift to cardiac gene therapy and new therapeutic options for heart diseases. Novel new technologies may also become widely applicable in other areas of medicine.

Keywords

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Programme(s)

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Topic(s)

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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.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2019-ADG

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Host institution

ITA-SUOMEN YLIOPISTO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 500 000,00
Address
YLIOPISTONRANTA 8
70211 KUOPIO
Finland

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 500 000,00

Beneficiaries (1)

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