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Mechanism-Based Integrated Systems for the Prediction of Drug-Induced Liver Injury

Objective

The current test systems employed by Industry are poorly predictive for Drug induced liver injury (DILI). The ‘MIP-DILI’ project will address this situation by the development of innovative preclinical test systems which are both mechanism-based and of physiological, pharmacological and pathological relevance to DILI in humans. An iterative, tiered approach with respect to test compounds, test systems, bioanalysis and systems analysis will be adopted to evaluate existing models and develop new models that can provide validated test systems with respect to the prediction of specific forms of DILI and further elucidation of mechanisms. The approach will encompass completely characterised cell lines, well-defined and physiologically stable hepatocytes, multi-cell type in vitro models including novel bioreactors, animal models and appropriate ex vivo human cell models. A systematic analysis of data and iteration at each stage will select the ‘best’ cell line, animal model or pathway for further investigation moving from simple systems to more complex models with reference to relevant clinical and preclinical data on the various forms of DILI. Triangulation of human, in vitro and animal data will provide a fundamental understanding of how drugs can harm the liver. It will then be possible to define the application of each particular novel test system in the context of drug development, and its use in the prediction of liabilities associated with the various forms of DILI that occur in man. Just as importantly, the project will define those models that are not appropriate as decision-making tools for the prediction of DILI in man.

The MIP-DILI consortium contains Key Opinion Leaders from academia, the biotechnology sector and the pharmaceutical industry in the fields of drug development, drug metabolism, drug toxicology, drug hypersensitivity, liver immunology, liver cell biology, pharmacogenetics, systems biology and clinical adverse drug reactions.

Call for proposal

IMI-JU-03-2010
See other projects for this call

Funding Scheme

JTI-CP-IMI - Joint Technology Initiatives - Collaborative Project (IMI)

Coordinator

ASTRAZENECA AB
Address
Vastra Maelarhamnen
151 85 Sodertaelje
Sweden
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
Dominic Williams (Dr)
Administrative Contact
Eva Lindgren (Dr)

Participants (27)

THE UNIVERSITY OF LIVERPOOL
United Kingdom
EU contribution
€ 2 863 103
Address
Brownlow Hill 765 Foundation Building
L69 7ZX Liverpool
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Pam Neagle (Ms)
STICHTING VU
Netherlands
EU contribution
€ 1 149 061
Address
De Boelelaan 1105
1081 HV Amsterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Bart Van Leijen (Drs.)
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 1 548 817
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Eva Gipperth (Ms)
UNIVERSITATSKLINIKUM BONN

Participation ended

Germany
EU contribution
€ 602 463
Address
Venusberg-campus 1
53127 Bonn
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Beate Becker (Ms)
SOLVO BIOTECHNOLOGY ZRT
Hungary
EU contribution
€ 477 128
Address
Kozep Fasor
6726 Szeged
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Szabolcs Hajdu (Mr)
UNIVERSITE DE RENNES I
France
EU contribution
€ 886 114
Address
Rue Du Thabor 2
35065 Rennes Cedex
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Yolaine Bompays (Mrs)
Interface Europe
Belgium
EU contribution
€ 725 580
Address
Rue Du Trone 12
1000 Bruxelles
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Marc Loher (Mr)
UNIVERSITEIT LEIDEN
Netherlands
EU contribution
€ 1 087 035
Address
Rapenburg 70
2311 EZ Leiden
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ton Brouwer (Mr.)
Takara Bio Europe AB
Sweden
EU contribution
€ 926 749
Address
Arvid Wallgrens Backe
413 46 Göteborg
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Anette Elmlund (Ms)
KaLy-Cell
France
EU contribution
€ 1 302 043
Address
Rue Du Général Leclerc
67115 Plobsheim
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Lysiane RICHERT (Prof)
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany
EU contribution
€ 956 615
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Activity type
Research Organisations
Administrative Contact
Ina Krischek (Dr)
ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Germany
EU contribution
€ 412 663
Address
Fahnenbergplatz
79098 Freiburg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Christian Jäger (Ass. iur)
CXR Biosciences Limited

Participation ended

United Kingdom
EU contribution
€ 471 939
Address
James Lindsay Place
DD1 5JJ Dundee
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Mike Piper (Dr.)
ABBVIE DEUTSCHLAND GMBH & CO KG
Germany
Address
Mainzer Str. 81
65205 Wiesbaden
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Frank-Christophe Lintz (Dr)
BRISTOL-MYERS SQUIBB COMPANY CORP
United States
Address
Park Avenue 345
10154 New York
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Mary Sondej (Executive Associate II)
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD.
United Kingdom
Address
Great West Road 980
TW89GS Brentford
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Sally Miles (-)
INSTITUT DE RECHERCHES INTERNATIONALES SERVIER IRIS
France
Address
Rue Carnot 50
92284 Courbevoie
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Daniel COURTOIS (Mr)
JANSSEN PHARMACEUTICA NV
Belgium
Address
Turnhoutseweg 30
2340 Beerse
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Henk Sipma (Dr)
H. LUNDBECK AS
Denmark
Address
Ottiliavej 7-9
2500 Valby
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Klaus Gjervig Jensen (Dr)
Merck KGaA
Germany
Address
Frankfurter Strasse 250
64293 Darmstadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ninog Péresse (Mrs.)
ORION OYJ
Finland
Address
Orionintie 1
02200 Espoo
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Reijo Salonen (Dr)
SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
France
Address
Pierre Brossolette 1
91380 Chilly Mazarin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Philippe Detilleux (Dr)
UCB BIOPHARMA
Belgium
Address
Allee De La Recherche 60
1070 Bruxelles
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Simon Dresse (Mr)
UNIVERSITEIT UTRECHT
Netherlands
EU contribution
€ 536 422
Address
Heidelberglaan 8
3584 CS Utrecht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Monique Van der Hoek (Ms)
LHASA LIMITED
United Kingdom
EU contribution
€ 552 494
Address
Granary Wharf House, 2 Canal Wharf
LS11 5PS Leeds
Activity type
Research Organisations
Administrative Contact
Elizabeth Marguerite Covey-Crump (Business Dev Mgr)
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN
Germany
EU contribution
€ 837 312
Address
Ismaninger Strasse 22
81675 Muenchen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Renate Rädlein (Ms.)
ELI LILLY AND COMPANY LTD
United Kingdom
Address
Lilly House Basingview
RG21 4FA Basingstoke
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Birgit Steckel-Hamann (Dr)