InoCardia: Cellular Work-Loop Proof of Concept

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Adverse effect of drugs on the cardiovascular system is a major cause for compounds failingin both non-clinical and clinical studies. Indeed, some of these adverse effects may only becurrently detected after the compound has been granted marketing approval and manythousands of patients treated. Thus such effects represent a significant issue for human healthand very high costs for the pharmaceutical industry. Although adverse drug effects on thecardiovascular system may be due to many effects, one area of great concern is the effect ofdrugs on the force of contraction of the heart. Some drugs can reduce the force of contractionsand cause symptoms similar to heart failure in susceptible patients whilst others can increaseit resulting in an imbalance between the amount of oxygen needed by the heart and thatsupplied by the blood.Currently, testing for drug effects on the force of contraction of the heart is very muchdependent on the use of animals (in-vivo tests) and / or low throughput assays using isolatedtissues (in-vitro tests). Given the nature of these studies testing is often conducted very late inthe drug discovery process. Furthermore, the predictive value of the available tests for humanrisk is limited. Thus, there is a need for more predictive assays with much greater throughputthat can be used to select compounds with much less effect on the heart.The goal of this project is to test the concept of a higher throughput functional cardiac cellcontractile assay under truly physiological conditions. It will essentially advance theinformation on how the heart behaves functionally and enable us to test inotropic drugs inthese conditions. If successful, we aim to develop a higher throughput assay to test manycompounds per week enabling selection of compounds for clinical trials that have less liabilityto adversely affect the contractility of the heart.