10 years of CRACK IT webinar: Chipping away at in vivo nephrotoxicity testing

  • NC3Rs
Wednesday 09 June 2021 14:00 to 15:00

This webinar forms part of the CRACK IT 10 year anniversary celebrations and will showcase the NephroScreen human kidney-on-a-chip platform that has the potential to replace in vivo nephrotoxicity studies in drug development. NephroScreen was developed to address the 2013 NephroTube CRACK IT Challenge sponsored by GSK, Pfizer and Roche.

Register via Zoom

NephroScreen is a microfluidic human kidney proximal tubule-on-a-chip platform developed by the organ-chip company Mimetas that can be used as an early in vitro screen for drug-induced nephrotoxicity. Consisting of 40 kidney proximal tubules per plate, the platform does not require complex pumps, making it suitable for high throughput and routine drug screening. It has been independently characterised at three different laboratories using two proximal tubule human cell lines and validated with 12 nephrotoxic compounds provided by the Sponsors and can accurately detect toxicities when compared with preclinical and/or clinical data. A typical investigative animal study to assess nephrotoxicity would use at least 26 rodents but this could be substantially more animals if both sexes were necessary. Applying NephroScreen early in drug development could significantly reduce these numbers.

During the webinar Dr Linda Gijzen (Project Scientist, Mimetas) will describe how Mimetas applied their enabling OrganoPlate® platform to develop perfused epithelial kidney tubules, how these were validated using the compounds provided by the sponsoring companies and how NephroScreen is being deployed in drug development. She will also highlight the technological developments Mimetas is leading on to deliver 3Rs products to address the Neuratect and In Vitro TDAR CRACK IT Challenges.

The webinar is free to attend.

Register via Zoom


Background:

The NephroTube Challenge, sponsored by GSK, Pfizer and Roche and launched in 2013, aimed to develop a multi-compartmental, microfluidic tissue assay to model the renal tubular injury observed in nephrotoxicity. The assay was to mimic the 3D architecture of the kidney tubules with microfluidics and chip arrays able to reproduce the tubular response to known nephrotoxicants. The Sponsoring companies posed the Challenge to create a more physiologically relevant, human-based model to address the high rates of drug failure attributed to nephrotoxicity not identified during preclinical development using traditional in vitro and animal models. The translational gap between the current preclinical toxicology models and their predictive value to the clinic means that compounds are tested in animals rather than being screened out early in development, or that standalone in vivo studies are required to investigate the relevance of a nephrotoxic signal.

The NephroTube Challenge was awarded to a team led by Dr Martijn Wilmer at Radboud University Medical Centre in the Netherlands and which included Mimetas who commercialised the technology.

Further information about the NephroScreen platform can be found on the NC3Rs Innovation Platform.