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Moving from whole genome cfDNA methylation to a PCR-based liquid biopsy assay for detecting high-risk atherosclerotic plaques

Project description

A new approach to heart disease detection

Diagnosing coronary artery disease (CAD) is a pressing challenge, with CAD accounting for 45 % of deaths in women and 39 % in men across the EU. Women’s CAD is often diagnosed later due to less recognisable plaque characteristics. This delay is critical as ischemic heart disease demands immediate attention. With this in mind, the ERC-funded U-BiomarCARE project seeks to address this issue by developing a PCR-based method to detect plaque-specific DNA methylation signals in plasma. If successful, this approach could revolutionise CAD detection, enabling timely and accurate identification of heart disease in both women and men, and opening doors to potential commercial applications in healthcare.

Objective

General practitioners and cardiologists are faced every day with challenging decisions on whom to refer for diagnostics of coronary artery disease (CAD) as sign and symptoms of cardiac ischemia require immediate action. Diagnosis of CAD is key as ischemic heart disease accounts for 45% of deaths in females and 39% in males in the European Union. Yet, diagnosis of CAD in women is regularly delayed and often unrecognized.
As the main pathology underlying CAD, it is essential to understand atherosclerotic plaque biology. In recent years, my research group and others have identified clear sex differences in the atherosclerotic plaque morphology and its (epi)genetic regulation. One consequence is that female plaques are more difficult to detect than male plaques, especially those which cause symptoms. As part of the ERC UCARE project, we uncovered a plaque-specific epigenetic signal in cell-free DNA from plasma of women with CAD. This signal consisted of hypomethylated regions specific for plaques that can be detected in plasma cell-free DNA. Our methods thus far have been focused on whole genome sequencing analyses. Yet, for studying the predictive value of these regions in large cohorts of patients with CAD, as well as exploring commercial potential, we need to develop a more specific methodology.
Our aim in this current U-BiomarCARE project is to investigate if the methylation status of plaque-specific regions can be detected in plasma with a PCR-based method. Once we prove that this methodology is reproducible and comparable to whole genome DNA methylation sequencing, we can perform large biomarker studies in both women and men suspected of heart disease and explore potential commercialization of plaque-specific cell-free DNA methylation profiles to accurately detect CAD. This will be a game changer for the healthcare sector as it will allow a specific and timely detection of dangerous atherosclerotic plaques both in men and women.

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2023-POC

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Host institution

UNIVERSITAIR MEDISCH CENTRUM UTRECHT
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.

€ 150 000,00
Address
HEIDELBERGLAAN 100
3584 CX Utrecht
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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