InoCardia: Cellular Work-Loop Proof of Concept

药物对心血管系统的不良反应是导致药物非临床和临床研究失败的主要原因。事实上，这些副作用中的一些可能只有在化合物被批准上市和成千上万的患者接受治疗后才能被发现。因此，这种影响代表了人类健康的一个重要问题，并且制药工业的成本非常高。尽管药物对心血管系统的不良反应可能是由许多作用引起的，但最令人关注的一个方面是药物对心脏收缩力的影响。一些药物可以降低收缩力，导致易感患者出现类似心力衰竭的症状，而另一些药物可以增加收缩力，导致心脏所需的氧气量与血液供应的氧气量不平衡。测试药物对心脏收缩力的影响在很大程度上依赖于使用动物（体内测试）和/或使用分离的组织的低通量测定（体外测试）。鉴于这些研究的性质，测试往往是在药物发现过程中进行的很晚.此外，现有的人类风险测试的预测价值是有限的。因此，有必要更多的预测分析与更大的throughputthat可用于选择化合物与心脏的影响小得多，这个项目的目标是测试的概念，更高的吞吐量功能性心肌细胞收缩试验在真正的生理条件下。它将从根本上推进心脏功能如何运作的信息，并使我们能够在这些条件下测试正性肌力药物。如果成功的话，我们的目标是开发一种更高通量的检测方法，每周检测许多化合物，从而为临床试验选择对心脏收缩力有较低不利影响的化合物。

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.