Predictive cross-species proximal tubule cell models for drug development and safety assessment studies

Date: February 25 2015
Presenter(s): Dr. Colin Brown, Ph.D.

Webinar was presented on February 25th, 2015 by Colin Brown, Ph.D., Associate Professor, Institute for Cell and Molecular Biosciences, Medical School Newcastle University, Newcastle, UK

Summary of the presentation

Accurate prediction of human drug toxicity is a major challenge in drug development as in vivo screening of new chemical entities (NCEs) in animal models often fails to predict subsequent human toxicity, leading to attrition at first in man. Kidney damage accounts for up to 20% of failures during the drug development pathway. The major roadblock to reducing drug attrition during development is the poorly predictive nature of current animal based screening models. It is estimated that up to 60% of animal studies fail to identify subsequent toxicity in man.

To address this issue we developed highly differentiated cell culture models of the human and rat kidney proximal tubule (aProximate cells), which recapitulate the physiology of the in vivo proximal tubule and when allied to a broad screen of toxicity, provide mechanistic and species-specific data about the nephrotoxic potential of NCEs. In this webinar, I will describe the properties of our in vitro proximal tubule models and using a number of case studies illustrate how it can be used to understand the handling of drug molecules by the proximal tubule.

Dr. Colin Brown is an Associate Professor in the Institute of Cell & Molecular Biosciences, Medical School, Newcastle, UK. He received his Bachelor and Ph.D degrees in Physiology and Pharmacology from the University of St Andrews, Scotland., He then held a Royal Society European Postdoctoral Fellowship, focusing on renal phosphate transport, at the Institute of Physiology, University of Zurich, Switzerland. After this he was awarded a prestigious Wellcome Trust Senior Research Fellowship in Biomedical Sciences which he held at the School of Medicine, University of Manchester UK. After a period in Manchester, he obtained tenure at the University of Newcastle as an Associate Professor. His research interests have centered around the study of the interaction of drug molecules with transport proteins in renal, hepatic and gastrointestinal epithelia. Most recently he has developed a series of novel proximal tubule cell models with which to investigate the handling of drug molecules. He holds consultancy positions with a number of Pharmaceutical companies.