Optogenetic Technique Screens for Cardiac Drug Safety

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An optogenetic technique has been used to make cardiac cells beat and optically measure their response, enabling an automated drug-testing process called OptoDyCE. The fully automated system for all-optical cardiac electrophysiology can rule out potentially dangerous drugs by testing 30,000 light-responsive cells in less than 10 min, a process that currently takes hours or even years.

Using optogenetics, "spark" cells (green) and automation, Professor Emilia Entcheva's lab at George Washington University speeds up the process of drug screening in heart cells (red) to help bring safer drugs to market. Courtesy of Christina M. Ambrosi. 

The technique streamlines the primarily manual process that researchers use to comply with FDA testing requirements and ensure the safety of the drugs. It can also be done using a patient's own blood cells using stem-cell techniques. One of the biggest challenges with developing new medications is testing to make sure treating the problem doesn’t cause any cardiac toxicity, according to professor Emilia Entcheva of George Washington University, senior author of the study.

The GW team reported validation of optical actuation by virally introducing optogenetic drivers in rat and human cardiomyocytes, or through the modular use of dedicated light-sensitive somatic “spark” cells. The optical stimulation and recording method offers noncontact, dynamic control of millions of cells, the researchers said.

"This not only allows you to perform faster testing but also provides a safer way to do measurements if you're testing hazardous materials,” said the study’s first author, doctoral student Aleks Klimas.

To achieve FDA approval, medications must be vetted to ensure they don’t pose a danger to the heart or any other part of the body. In the earliest phases of testing, cells are treated with the medication to see how they react. The most reliable method has been to measure their response manually, by directly inserting probes into the cell, with high-throughput technologies speeding up this practice. However, until now, no such high-throughput system has been available for work with actual heart cells.

Separate from uses in the drug discovery arena, the method could also be used to confirm that stem cells have properly matured into heart cells, which could improve the quality of newly created heart cells and speed up their deployment in the clinic.

The technology could appeal to pharmaceutical companies looking to expedite the drug development process, and Klimas hopes to commercialize the idea and develop a business to market the device.

The research was published in Nature Communications (doi: 10.1038/ncomms11542).

Published: June 2016
A discipline that combines optics and genetics to enable the use of light to stimulate and control cells in living tissue, typically neurons, which have been genetically modified to respond to light. Only the cells that have been modified to include light-sensitive proteins will be under control of the light. The ability to selectively target cells gives researchers precise control. Using light to control the excitation, inhibition and signaling pathways of specific cells or groups of...
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