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Mucosal protease and their inhibitors in inflammatory bowel disease: From etiopathogenetic insight to innovative therapy

Objective

IBDase addresses the etiology and pathogenesis of inflammatory bowel disease (IBD) with a multidisciplinary plan for innovative diagnosis and therapy focused on mucosal proteases and their inhibitors (P/PIs). The incidence of IBD, a multifactorial disease influenced by environmental factors in a background of complex genetic susceptibility, is rising, particularly among European children. Current therapies lack efficacy and specificity. The gut microflora plays a crucial role in IBD but the cause for this is still poorly understood. Research implicating P/PIs in gut mucosal inflammation requires further mechanistic insight and the P/PIs relevant in human IBD need to be identified. To this end we will identify human mucosal P/PI polymorphisms affecting expression levels and/or activity of P/PIs and analyse their genotype/phenotype associations in IBD patient cohorts across Europe. IBD-associated P/PIs will be characterised by biochemical properties, expression in human clinical samples and manipulation of experimental models. Their interaction with microflora will be examined in animal models with controlled colonisation of the gut and in vitro co-culture models of intestinal mucosa and bacteria. In vivo studies will use targeted, well-established and new mouse models and evaluate zebrafish as an IBD model. Molecular mechanisms for involvement of IBD specific P/PI gene variants in the inflammatory response will be proposed. Therapeutics development will focus on specific inhibition or promotion of proteolysis in the intestinal mucosa, and select at least three validated P/PI of the intestinal mucosa for follow-up in clinical trials. Embracing the concept of tailoring treatment to individual patient characteristics to increase efficacy and reduce side-effects, IBDase strengthens international visibility of IBD related research, policies and industry and fosters IBD related research to the benefit of European society in both patient care and economic interest.

Field of science

  • /medical and health sciences/clinical medicine/gastroenterology/inflammatory bowel disease

Call for proposal

FP7-HEALTH-2007-A
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Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

UNIVERSITAET BERN
Address
Hochschulstrasse 6
3012 Bern
Switzerland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 526 950
Administrative Contact
Daniel Lottaz (Dr.)

Participants (9)

KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium
EU contribution
€ 305 000
Address
Oude Markt 13
3000 Leuven
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Marion Wolpers (Ms.)
UNIVERSITE D'AUVERGNE CLERMONT-FERRAND 1
France
EU contribution
€ 247 400
Address
Boulevard Francois Mitterand 49
63001 Clermont Ferrand
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Laurent Claret (Dr.)
JOHANNES GUTENBERG-UNIVERSITAT MAINZ
Germany
EU contribution
€ 88 400
Address
Saarstrasse 21
55122 Mainz
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Karl Peter Christian Spath (Dr.)
PROGENIKA BIOPHARMA SA
Spain
EU contribution
€ 533 650
Address
Parque Ibaizabal Bidea Edificio 504 Parque Tecnologico Derio
48160 Vizcaya Bizkaia
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Gorka Ramirez (Dr.)
ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy
EU contribution
€ 314 550
Address
Via Filodrammatici 10
20121 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ilaria Foti (Ms.)
GOETEBORGS UNIVERSITET
Sweden
EU contribution
€ 258 200
Address
Vasaparken
405 30 Goeteborg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Margareta Ahlqwist (Prof.)
UNIVERSITY OF SOUTHAMPTON
United Kingdom
EU contribution
€ 387 800
Address
Highfield
SO17 1BJ Southampton
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Rachel Green (Ms.)
UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA
Italy
EU contribution
€ 175 400
Address
Via Cracovia 50
00133 Roma
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Francesco Pallone (Prof.)
SCIPROM SARL
Switzerland
EU contribution
€ 136 200
Address
Rue Du Centre 70
1025 Saint Sulpice
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Kirsten Leufgen (Dr.)