Validation of novel immunotherapeutic targets against fibrosis in inflammatory bowel diseases

Informations projet

FIBROTARGET

N° de convention de subvention: 101080523

DOI

10.3030/101080523

Date de signature de la CE 24 Avril 2023

Date de début 1 Avril 2023

Date de fin 31 Mars 2028

Financé au titre de

• Health

Coût total

€ 5 686 450,00

Contribution de l’UE

€ 5 686 450,00

Coordonné par

KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium

Periodic Reporting for period 1 - FIBROTARGET (Validation of novel immunotherapeutic targets against fibrosis in inflammatory bowel diseases)

Période du rapport: 2023-04-01 au 2024-09-30

Résumé du contexte et des objectifs généraux du projet

The FIBROTARGET project aims to transform the therapeutic landscape for intestinal fibrosis in inflammatory bowel diseases (IBD), particularly Crohn's disease (CD). Intestinal fibrosis, often leading to strictures, significantly impacts patients' quality of life and remains an unmet clinical need due to the lack of effective anti-fibrotic therapies. FIBROTARGET addresses this challenge through a multidisciplinary approach to understand fibrosis mechanisms, identify biomarkers, and develop innovative diagnostic tools and treatments.

Key objectives include:

Identifying and validating fibrosis-associated molecular signatures using advanced techniques such as single-cell RNA sequencing and spatial transcriptomics.

Preclinical evaluation of inhibitors targeting pathways like C3, Tyk2-STAT3, and NLRP3 inflammasomes in patient-derived tissues and experimental models.

Development of non-invasive imaging tools such as magnetic resonance enterography (MRE) integrated with artificial intelligence for fibrosis diagnosis and monitoring.

Designing and conducting the first-in-human trials of novel immunotherapeutics for fibrosis in CD.

Ensuring broad dissemination, patient engagement, and a sustainability plan for real-world impact.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

In its first reporting period, FIBROTARGET has:

Identified pathogenic fibroblast subsets and validated potential fibrosis biomarkers in IBD samples.

Demonstrated anti-inflammatory and anti-fibrotic effects of key inhibitors in preclinical models, showing promise for translation into clinical settings.

Advanced imaging techniques (MRE and MSOT) with AI integration for fibrosis detection, streamlining patient diagnostics and clinical trial design.

Engaged with regulatory bodies, industry partners, and patient organizations, ensuring alignment of project outputs with clinical and societal needs.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

FIBROTARGET has:

Uncovered the role of the NLRP3 inflammasome in fibroblast activation and collagen production, offering new therapeutic avenues.

Validated fibrosis-associated markers through high-resolution spatial transcriptomics and proteomics, paving the way for precision diagnostics.

Integrated imaging and AI technologies for reproducible, non-invasive assessment of fibrosis, setting a benchmark for future diagnostics.

Explored the potential of complement inhibitors like Cp40 to disrupt profibrotic pathways in human and experimental models.