Solution: In vitro models for kidney toxicity

Through CRACK IT Solutions, Dr Colin Brown from Newcastle University has secured a seven figure investment and a new partner to make commercially available his primary human kidney proximal tubule cell model for nephrotoxicity testing (aProximateTM).

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. A drug failing this late in development represents a significant financial burden on companies and increases the time it takes medicines to reach the clinic and patients. This also represents a substantial waste in animals used during the development of the drug. Most toxic and drug-induced injuries in the kidney occur in the proximal tubules, leading to calls for the development of more predictive human tissue-based in vitro proximal tubule models to assess nephrotoxicity.

Dr Brown's aProximateTM proximal tubule model has been developed to address this. Primary cells are grown as monolayers on permeable filter supports and maintain the full complement and expression level of endogenous renal transporters. This provides for the first time models which allow both a mechanistic and predictive understanding of drug transporters and drug-drug interactions to better predict the potential of a compound to induce renal toxicity in humans. The system is available as human, rat and mouse models for comparisons between toxicologically relevant species and man.

Using the CRACK IT Solutions technology partnering hub, Dr Brown was able to engage with SOLVO Biotechnology, a leading worldwide provider of transporter assay services and products. As a result, SOLVO and Dr Brown have signed an agreement for SOLVO to include aProximateTM in their portfolio of renal transporter assays offered to clients, making the technology available to a global customer base and maximising the potential 3Rs and drug development benefits.