To develop a multi-compartmental, microfluidic tissue assay that models the renal tubular injury observed in nephrotoxicity. The assay should model the 3D architecture of the kidney tubules with microfluidics and chip arrays and possess the ability to reproduce the tubular response to known nephrotoxicants.
Drug-induced organ toxicity accounts for 30% of all drugs that fail prior to reaching the market. Within this, nephrotoxicity accounts for 2% of failures in the preclinical stages and 19% of all failures in Phase III. There is a significant translational gap between the preclinical models of nephrotoxicity and their predictive value through the clinical stages of drug development. Current cell-based models can provide valuable information but do not accurately predict toxicity in humans. A more complex, human tissue-based, in vitro model that can accurately measure toxic effects would reduce the failure rates from preclinical to clinical stages of development by providing a more relevant model.
A Challenge to develop predictive in vitro screens for nephrotoxicity was featured in the CRACK IT 2011 Competition. No awards were made and the Challenge has now been amended to capitalise on novel microfluidic technologies that have recently become available and focus on human tissue systems rather than multiple preclinical species.
- A typical investigative animal study to assess nephrotoxicity would use at least 26 rodents (and substantially more animals if both sexes were necessary). New in vitro technologies that replace the need for animal use in toxicity testing could significantly reduce these numbers
- Use of predictive human systems in preclinical toxicology testing will reduce the drug attrition that results from poor translation from preclinical studies into humans
- Where animals are still used, information on the underlying mechanisms of toxicity will help refine study designs including dosing regimes and species selection
Phase 1 winners
Project teams led by:
- Dr Colin Brown, Newcastle University, £99,726.
- Dr Paul Jennings, Medizinische Universität Innsbruck, £99,330.
- Dr Roisin Owens, Ecole Nationale Supérieure des Mines de St. Etienne, £100,000.
- Dr Martijn Wilmer, Radboud University Medical Center, £99,323.
Phase 2 winner
Project team led by:
Full Challenge information