FIBROTARGETS sets out to develop a European Union (EU) led, global research consortium that focuses on Myocardial Interstitial Fibrosis (MIF) in HF, with the aim of validating new targets for further drug discovery and development to prevent/decrease MIF and slowdown the transition to and progression of HF.
The FIBROTARGETS project will lead to:
- the validation of biology-driven targets which, in turn,
- will result in both a better knowledge of the pathophysiology and modulation of myocardial interstitial fibrosis (MIF),
- identification and screening of small molecules with therapeutic potential aimed at the most promising biotargets,
- improved individualized options for HF prevention and treatment.
Ultimately, the FIBROTARGETS data will increase the probability of identifying new therapeutic molecular targets, druggable hits, and biomarkers with high clinical applicability
Strategy and Area of focus
The work plan of FIBROTARGETS is based on 6 sub objectives :
- Provide further evidence on the mechanisms of action of the selected MIF targets to understand the future mechanisms of action of the novel therapeutics and to drive the search for the best hits to interfere with these targets as well as to assess their efficacy.
- Validate experimentally that new anti-fibrotic strategies can be directed toward the above targets to strengthen the characterization of the therapeutic potential of these targets with observational and interventional experimental studies in already existing and/or de novo generated appropriate in vitro and in vivo models.
- Identify hits interfering with these targets by using up-to-date approaches to identify the best hits including in silico design, and chemoinformatics for the selection of chemical and natural compound libraries.
- Identify biomarkers of the in vivo activity of the biotargets and develop corresponding bio-assays. These biomarkers - bioassays will be used to assess the efficacy of the selected candidate therapeutic molecules on fibrosis production and for the iterative optimisation of this efficacy.
- Test the relevance of these targets into a small large animal preclinical model of HF with MIF, with serial biomarker and imaging assessment of progression-regression of fibrosis and of cardiac remodelling. This will validate the implication of the targets in MIF and the potential efficacy of the newly develop hits in a preclinical model closer to human and therefore to accelerate the future translation to patients.
- Clinical studies, screening/stratifying large-scale populations of patients based on specific "fibrogenetic" phenotypic profiles using multi-panel imaging and circulating markers descriptive of mechanisms involving the proposed novel targets. FIBROTARGETS studies will help evaluating the clinical potential and clinical applicability of our findings by assessing patients likely to be responsive to therapies aimed at the mechanistic target pathways identified by the consortium.