Project Summary
Heart disease remains the leading cause of mortality in the world and, drug-induced cardiotoxicity is a major
cause of drug failure and withdrawal from the clinic or the market, contributing to the poor overall success rate
of drug development programs. In vitro models of cardiac contractility have the potential to generate predictive
data earlier in the pipeline to reduce later-stage failure due to cardiotoxicity, and enable discovery and
development of effective therapeutics more likely to successfully translate in the clinic. Such cardiac contractility
models could serve as valuable high-throughput phenotypic screening tools for target-guided (antagonistic) or
target-agnostic discovery of contraction-modulating agents (e.g. small molecules, biologics, RNAi) that enhance
or rescue the healthy phenotype. Similarly, a high-throughput cardiac contractility assay system could be used
to test possible treatments in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM)
to identify patient specific “precision medicine” treatments. Unfortunately, no single solution address all of the
key needs of the end-user and in existing technologies reporting mechanical endpoints, electrical pacing
capabilities have come at the expense of throughput. This STTR proposal will deliver an integrated product
addressing these needs by combining an optimized version of Forcyte’s FLECS contractility assay with a
proposed novel “Pace-Cap” electrical pacing system designed for the standard well-plate format that will be
embedded directly on the microplate lid. In aim, a 24-well prototype of the in-lid electrical pacing mechanism will
be developed and validated using calcium flux as a preliminary readout. In aim 2, Forcyte’s contractility platform
will be developed into a cardiac micro-tissue evaluation platform and the resulting assay will be used to mechano-
functionally validate the Pace-Cap. If successful, this would represent the first all-in-one cardiac contractility
assay kit that is both high-throughput and has internal pacing capabilities. Phase 2 work will focus on extending
the prototype throughput to 96-wells and developing rapid production strategies.
