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.
Fields of science
Call for proposal
IMI-JU-03-2010
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Coordinator
151 85 Sodertaelje
Sweden
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Participants (27)
L69 7ZX Liverpool
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1081 HV Amsterdam
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17177 Stockholm
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Participation ended
53127 Bonn
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6726 SZEGED
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35065 RENNES CEDEX
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1000 Bruxelles
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2311 EZ Leiden
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413 46 Göteborg
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67115 Plobsheim
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69120 Heidelberg
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79098 Freiburg
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Participation ended
DD1 5JJ Dundee
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65205 Wiesbaden
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10154 New York
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TW89GS Brentford
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92284 Courbevoie
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2340 Beerse
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2500 Valby
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64293 Darmstadt
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02200 Espoo
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94250 GENTILLY
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1070 Bruxelles / Brussel
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3584 CS Utrecht
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LS11 5PS Leeds
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81675 Muenchen
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RG21 4FA Basingstoke
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