To reach these aims the following studies will be performed:
- Observational and interventional experimental studies in existing and/or de novo generated appropriate in vitro and in vivo models.
- Clinical studies involving large scale patient populations (available within the consortium) at risk for developing HF and likely to respond to specific novel and/or existing anti-fibrotic therapies. Patients will be stratified according to specific "fibrogenetic" phenotypic profiles using multi-panel imaging and circulating markers reflective of mechanisms involving the proposed novel targets.
Recently the term 'theragnostics' has been coined to formally describe a strategy that combines diagnostic tests with therapeutic intervention. Theragnostics covers a range of approaches such as pre-treatment identification of patient subgroups that are likely to respond to therapy or are at higher risk of drug side-effects; and monitoring of drug efficacy and safety once treatment is commenced.
Ideally, a successful theragnostic approach may result from the biomarker and drug target being the same molecular entity. One important objective of the FIBROTARGETS project is to develop biomarkers and corresponding bioassays that track with the validated novel therapeutic targets of MIF. Ideally, drug molecular targets will be assessed as to their potential to serve as biomarkers.
Markers emerging from the work and that will be found to be more specifically associated with MIF mechanistic pathways, will be tested individually or integrated into a multi-marker risk panel with regard to their ability to predict pharmacological response to anti-fibrosis therapies.