Novel Methods to Evaluate the Cardiac Activity of Pharmaceuticals: Identifying New Therapies and Predicting Cardiac Toxicity

在加拿大，心力衰竭是死亡和残疾的主要原因，造成了巨大的医疗和社会经济成本。开发治疗心力衰竭的新疗法是具有挑战性的，主要是因为我们没有好的方法来模拟心脏细胞的活动。同样，已知某些药物对心脏有不良影响(特别是癌症和化疗药物)，尽管不良反应的程度是巨大的。确定患者可以(或不能)安全地接受哪些药物也存在缺乏正确模拟心脏活动的能力的问题。我们的合作小组合作开发了新的方法来测量心脏细胞功能，以准确地反映患者体内发生的情况。作为这项工作的一部分，我们正在开发一种新的平台设备，使用碳纳米管来量化心脏细胞的复杂功能。该设备将允许同时测量心脏细胞功能的关键组成部分心跳频率、心跳节律和收缩能力(心脏细胞，从而心脏，可以挤压多少血液)。目前还没有单一的设备可以量化所有这些指标，这限制了治疗心力衰竭的新药的开发，并限制了对药物潜在心脏损害的测试。使用来自对心脏毒性药物有严重反应的患者的心脏细胞，我们将展示我们如何预测这些患者发生的心力衰竭，以及我们的设备将如何能够指导治疗选择。利用患者来源的心脏细胞的创造，我们的平台技术将允许对心脏细胞活动进行准确的建模，从而开发治疗心力衰竭的新药，或确定特定患者是否可以接受某种药物治疗，而不会对心脏产生不良影响。

Heart failure is the leading cause of death and disability within Canada, creating significant medical and socioeconomiccosts. Developing new therapies for heart failure is challenging, primarily because we do not have good ways to model theaction of heart cells. Similarly, certain medications are known to have adverse effects on the heart (particularly cancerchemotherapeutics), although the degree of adverse effect is tremendous. Determining which medications a patient can (orcannot) receive safely also suffers from the lack of ability to properly model the action of the heart. Our collaborative grouphas worked together to develop new ways to measure heart cell function in ways that accurately represent what happens inthe patient. As part of this work, we are developing a new platform device that uses carbon nanotubes to quantify thecomplex function of the heart cell. This device will allow for simultaneous measurement of the key components of heart cellfunction beating rate, beating rhythm and contractility (how much the heart cell, and therefore the heart, can squeeze bloodout). There is currently no single device that can quantify all of these metrics, limiting the development of new medicationsfor heart failure and limiting the testing of medications for their potential damage to the heart. Using heart cells derived frompatients who have had severe reactions to heart toxic medications, we will show how we could have predicted the heartfailure that occurred in these patients, and how our device would have been able to guide therapy choices. Capitalizing onthe creation of patient-derived heart cells, our platform technology will allow for accurate modeling of heart cell action,leading to the development of new medications for heart failure or determining if a particular patient can receive a certaindrug without experiencing adverse effects on the heart.