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

在加拿大，心力衰竭是导致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具有挑战性，主要是因为我们没有很好的方法来模拟心脏细胞的活动。同样，某些药物对心脏也有不良影响（尤其是癌症化疗药物），尽管不良影响的程度是巨大的。确定患者可以（或不可以）安全地接受哪些药物也受到缺乏正确模拟心脏活动能力的困扰。我们的合作小组共同努力开发新的方法来测量心脏细胞的功能，以准确地反映病人的情况。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：心率、跳动节奏和收缩力（心脏细胞，也就是心脏，可以挤出多少血液）。目前还没有一种设备可以量化所有这些指标，这限制了心力衰竭新药的开发，也限制了药物对心脏潜在损害的测试。使用来自对心脏有毒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，以及我们的设备如何能够指导治疗选择。利用患者衍生心脏细胞的创造，我们的平台技术将允许对心脏细胞行为进行准确建模，从而开发新的心力衰竭药物，或确定特定患者是否可以接受某种药物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.