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Validation of novel immunotherapeutic targets against fibrosis in inflammatory bowel diseases

Objective

Fibrostenosis is the driving reason for the persistent need in bowel resections in inflammatory bowel diseases (IBD). Current IBD therapies are limited to solely targeting inflammation. While these therapies in some, but not all, cases lead to symptomatic disease remission, recurrent flares interspaced with periods of remission will still result in cumulative gut wall remodeling and fibrosis. Indeed, despite these therapeutic strategies to control inflammation, fibrostenosis incidence and bowel surgical resection is not declining in IBD patients, as no anti-fibrotic drugs are currently available. The aim of this project is to validate fibroblast therapeutic targets for preventing and/or treating fibrosis in IBD-patient-samples with an emphasis on C3 and/or Tyk2/STAT3 and/or NLRP3 in the evolution of intestinal fibrosis. The anti-fibrotic efficacy and mode of action of these novel immunotherapies will be studied preclinically in IBD-patient derived samples and validated in animal models of chronic colitis. In parallel, we aim to develop and validate a clinical diagnostic and prognostic pathway for fibrosis in IBD patients based on the use of non-invasive cross-sectional imaging techniques such as magnetic resonance enterography with elastography and optoacoustic. These results together will allow to design a first-in-human proof of concept randomized trial of immunotherapeutic drugs targeting complement C3 and/or Tyk2/STAT3 and/or NLRP3 pathways in intestinal fibrostenosis. Our aim is to obtain patients and regulatory approval for implementation of these novel non-invasive imaging modalities as diagnostic and prognostic tools for fibrotic IBD to allow vital future therapeutic development for intestinal fibrosis. By providing better molecular and clinical stratification of IBD patients at risk for fibrosis and by identifying and validating novel targets for anti-fibrotic therapy, we aim to pave the way in preventing and treating this invalidating IBD comorbidity.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-RIA - HORIZON Research and Innovation Actions

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Call for proposal

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(opens in new window) HORIZON-HLTH-2022-DISEASE-06-two-stage

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Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
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.

€ 2 442 812,50
Address
OUDE MARKT 13
3000 LEUVEN
Belgium

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Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 442 812,50

Participants (8)

Partners (1)

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