Platform for Screening for Chemotherapy-Induced Cardiotoxicity

Background & Unmet Need

• Cardiotoxicity is a major concern for patients receiving chemotherapy, as well as the development of new chemotherapeutic drugs
• Of the 50% of cancer patients that receive chemotherapy, between 5–25% of survivors develop chemotherapy-induced cardiovascular diseases
• Moreover, cardiotoxicity is a leading cause of failure for new chemotherapy drug development
• Chemotherapy-induced toxicity affects multiple cardiac cell types, including both cardiomyocytes and pacemaker cells
• Current cardiotoxicity screens only evaluate cardiotoxicity to cardiomyocytes, but not pacemaker cells
• Unmet Need: Methods for screening drugs that protect both cardiomyocytes and pacemaker cells from chemo-induced cardiotoxicity

Technology Overview

• The Technology: A human stem cell-based platform to screen for cardioprotective drugs
• The Discovery: The inventors have developed a method of generating and isolating sinoatrial node (SAN) cells, also known as pacemaker cells, from human embryonic stem cells
• These SAN cells can be used as part of a platform for screening chemotherapeutic drugs for cardiotoxicity
• PoC Data: SAN cells generated using this system demonstrate molecular and electrophysiological characteristics of pacemaker cells
• A candidate cardioprotective drug, CardioPro, has been identified which protects heart cells from doxorubicin-induced cardiotoxicity in vitro and in vivo

Technology Applications

• Screening platform for identifying cardioprotective drugs
• Prevention of chemotherapy-induced cardiotoxicity using CardioPro drug candidate
• Platform for modeling other cardiac diseases such as cardiomyopathy

Technology Advantages

• Platform integrates both pacemaker and cardiomyocyte cell types, providing a more complete picture of cardiotoxicity than current platforms
• Isolation of pacemaker and cardiomyocytes, as well as analysis of cardiotoxicity, is made easier by the development of several reporter lines

Figure 1: Schematic of screening platform for cardioprotective drugs.