EIC Pathfinder Challenge: Cardiogenomics

Cardiogenomics holds the potential to address existing gaps in the diagnosis and treatment of cardiovascular diseases (CVD), which would enable better outcome for the patient. Advanced genetic testing taking into account complex inheritance, or combining genetic testing, transcriptomics, proteomics and metabolomics analysis with clinical phenotype can improve clinical management of the CVD and identify more accurately, who is likely to be at risk for major cardiovascular events such as heart failure or sudden death. Many gene variants associated with CVD are of unknown significance and thus of limited clinical utility. Our ability to sub-classify CVD diseases according to their underlying molecular mechanism has been enhanced due to technological approaches such as, spatial or single-cell transcriptomics, and others.

There has been considerable funding in the past directed to support and improve the quality of life of patients with severe heart and other CVD conditions (e.g. development of bio-electronic implants/devices). On the other hand, there has been considerably less public funding allocated to demanding research targeted to the actual cause of major CVDs and their complex genetic basis and as a result, limited progress has been made in this front. Although, the complex genetic basis of some of the inherited cardiovascular conditions, such as, the cardiomyopathies is widely accepted, it remains far from being elucidated. In addition, already identified gene variants can demonstrate variable expressivity (clinical phenotype severity), challenging the clinical interpretation of the variants identified in a patient and the selection of the therapeutic tool. As per the major common diseases such as heart attack and atrial fibrillation, the genetic basis is incompletely understood.

Companies are therefore increasingly raising funding to support their preclinical CVD programs aimed to develop key molecules that can disrupt signalling pathways that regulate key cardiovascular processes including rhythm, hypertrophy, contractility, and autophagy and others, potentially leading to new therapies for heart failure or other CVD conditions. The overall aim of this Challenge is to pave the way for novel therapies for major CVD conditions including hemorrhagic and ischemic stroke, aneurysm, cardiomyopathy and certain types of arrhythmias and other conditions, for which no effective treatments are currently available.

The gender dimension in research content should be considered, where relevant.

Specific objectives

The following specific objectives have been identified for this Challenge:

• to identify single or multiple gene variants of high biological significance or other key molecules associated with the CVDs that would allow for accurate stratification of patients and guide the physician in their clinical management and monitoring of these CVDs;
• to identify novel targets based on these variants for specific CVD indication(s) that would allow for the development of first in class therapies for the same indication;
• to seek for novel technological solutions that could contribute to the development and acceleration of first in class therapies for major CVD conditions for which no effective treatments are currently available.

Expected outcomes and impacts

The following major impacts can be foreseen for this Challenge:

• impact on the practice of cardiology: identification of pathogenic mutations or multiple variants that have actionable effects (by disrupting normal biochemical pathways associated with the cause and/or progression of the disease), will have a substantive impact on the practice of cardiology;
• accelerating the implementation of personalised care in CVD: deciphering the molecular pathogenesis underlying the clinical pathology of a CVD disease, is key for implementing personalised care. Performing targeted DNA sequencing on CVD patient(s) to identify previously characterised pathogenic mutations, is expected to become part of the daily clinical routine in the CVD clinics. Targeted genetic testing is envisaged to serve a triple purpose:
  • • to achieve an early and more accurate diagnosis;
    • to guide the physician to administer the right treatment for the right patient (personalised treatment); and
    • to predict more accurately post treatment clinical course (favorable or non- clinical prognosis).
• gathering the necessary knowledge and data that would enable to apply disease modelling for CVD, including through 3D in-vitro models, to be used for screening drugs/therapies for CVDs.

Specific conditions

Applicants must convincingly demonstrate that they have access to a large cohort of genomic and/or transcriptomics and/or proteomics and/or metabolomics database from CVD patients.

For more details, see the EIC Work Programme 2022 and Challenge Guide for this topic (available on call opening).