*JASON MAYNES

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

Challenge: Current therapies for heart failure primarily relieve symptoms, but most fail to correct organ dysfunction. New therapies, to target and improve cardiomyocyte function, are challenging to develop because of the complex functions of the heart muscle and the difficulty in modeling heart cell behavior. The same problems underlie the difficulty in assessing the cardiotoxic side effects of drugs. There is, therefore, an unmet need for assays that measures the comprehensive functions of cardiomyocytes to develop safe non-cardiology drugs and new cardiac therapeutics.

Solution: The team developed a novel sensor, capable of comprehensively profile the function (beating rate, rhythm, and contractility) of 2D layers of cardiac tissue generated from human stem cell-derived cardiomyocytes. The microdevice consists of a deformable membrane with embedded carbon nanotubes-based strain sensors and polydimethylsiloxane (PDMS). Cardio-toxicity of known or new drugs could thus be determined in this long-term (14 days) culture of human cardiomyocytes.

Achievements/Impact: The team successfully developed their device and incorporated fluorescent beads to better track in three-dimension the contractility signals. The system was successfully validated and tested using known cardio-active drugs (isoproterenol, verapamil, omecamtiv, ivabradine), and a pharmacologic arrhythmogen (E4031). All compounds generated the expected physiologic responses. The team also filed a patent application to protect their device and are actively looking to commercialize it.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigator:


Jason Maynes
University of Toronto;
Hospital for Sick Children

Co-investigators

Yu Sun
University of Toronto

Completed Project
$ 300,000 / 2 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• Boehringer Ingelheim
• GSK
• Janssen
• Novartis
• Sanofi
• BL-NCE
 
And by a co-funding partner:
• Ontario Centres of Excellence