Grid of Responses Indicating Drug Sensitivity

Unmet Need
Drug development is a long and costly process characterized by a high degree of attrition. Cardiotoxicity is the most common reason for withdrawing candidate drugs from the development pipeline, with 30% of drugs withdrawn during the clinical development phase. Improvements in methodologies for assessing drug cardiotoxicity during preclinical testing would both remove dangerous drugs early on from the pipeline and retain effective drugs, providing cost savings. The general approach to cardiotoxicity testing has been to evaluate a drug’s cardiotoxicity in animal models and in binding assays. However, this approach does not capture the biological complexity of human cardiac cells and can result in inaccurate assessment. Recently, new assays have been developed that use human-derived cardiac preparations to improve drug screening. However, these assays measure spontaneous activity of cardiac preparations and do not account for variables that influence drug responses. Consequently, novel, more accurate analytical tools are needed to assess the response of cardiac preparations to candidate drugs.

Technology Overview
The Grid of Responses Indicating Drug Sensitivity (GRIDS) assay is a method for testing the sensitivity of a cardiac preparation to drugs. This analysis software provides a framework for analyzing the responsiveness of cardiac preparations to a range of drug doses and pacing rates.This approach can be used on numerous cardiac preparations, including single cells, monolayers, cell clusters, engineered tissues, and tissue explants. GRIDS analysis can also be used to compare the level of electrophysiological maturity of cardiac preparations. Importantly, because it incorporates a categorical readout, GRIDS analysis can be adapted for high-throughput drug screens.

Stage of Development
Currently, this technology is ready to be incorporated into drug testing protocols and analysis software. Additionally, software could be written for the end user.


 

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