Electronic Optimization of Stem Cell Derived Human Cardiac Myocytes

Period of Performance: 07/01/2015 - 12/31/2015

$242K

Phase 1 STTR

Recipient Firm

Cytocybernetics, Inc.
North Tonawanda, NY 14120
Principal Investigator

Abstract

DESCRIPTION (provided by applicant): As part of the FDA approval process for novel therapeutic drugs, safety screening demonstrating that the new drug does not have deleterious effects on the human cardiac action potential is required. Healthy human heart cells are not available for such preclinical drug testing. There is currently no consensus on the best experimental approach to provide the most efficient, economical and faithful determination if the drug is likely to lengthen the cardiac action potential (Long QT) and result in the potentially fatl arrhythmia known as Torsade de Pointes. The FDA is actively seeking new reliable models for preclinical drug testing. Recently, Human cardiac myocytes were derived from induced pluripotent stem cells (iPSCDCMs). Human iPSCDCMs cells are in plentiful supply, and are able to withstand comprehensive electrophysiology to determine the drug-cell interactions. Although most ionic currents in these cells closely resemble those from freshly isolated heart cells, one important channel is missing: The inward rectifier current, IK1. As a result of this missing current, the cells do not have a physiological resting potential, are spontaneously active, and have an anomalous response to drugs. Viral transfection of Kir2.1, the molecular basis of IK1, has proved difficult, resulting in foreshortened action potentials, or complete lack f ability to stimulate action potentials at all. We have developed a novel technology, which restores IK1 using electronic expression. Using a mathematical model, IK1 is almost instantaneously calculated, based on the membrane potential of the cell. The calculated current is then applied to the cell electronically through an electrode, resulting in a virtual IK1, which interacts with the other membrane currents. Synthetic IK1 is easily adjusted to be appropriate for cell type and cell capacitance. The Phase I goal is to develop and optimize this research equipment into a reliable, robust, easy to use, "plug and play" device. The first set of milestones center on development of a commercial prototype: we will optimize the electronics, the software, and the system. Next, we will deploy the device in the lab, and determine benchmarks and performance attributes which will be needed to validate and sell the device. Completion of these Phase I milestones will position us to undertake drug testing and further validation in Phase II. Our technology will deliver a rapid and precise human cardiac action potential model, suitable for preclinical drug testing. This will have a significant impact on human health, as well as a strong economic impact. Our device enables easy identification of atrial and ventricular iPSCDCMs, thus increasing reliability of results, and reducing the number of experiments required for statistical significance. Our approach uses Human cells, which also reduces the likelihood of false positives/false negatives. This improved preclinical safety testing will more accurately identify drugs with adverse side effects earlier in the development process. This improved accuracy will avoid wasted expenditures on unsuccessful candidate compounds and will reduce the abandonment of potentially beneficial drugs.