Heart safety of new drugs tested with optogenetics

University of Helsinki researchers are using a method based on optogenetics to determine cardiac safety of new drug molecules at the early stages of drug development.

Even though new drug molecules undergo a very stringent pre-clinical testing process, they may still cause serious adverse effects, which—at worst—are only detected after more widespread clinical use. Typically, these effects target the heart; they cause arrhythmias and weaken the heart muscle’s ability to contract.

At the moment, heart safety of new drug molecules is tested using the patch-clamp technique on single cells and specific ion channels as well as by animal toxicity studies. These methods are both time-consuming and labour-intensive, and are in several aspects less than optimal in their abilities to predict serious adverse effects the compounds could have in humans.

 “We need reliable, predictive testing methods which could, at the very early stages of the drug discovery process, provide information on those molecular structures that may provoke cardiac arrhythmias,” says Professor Eero Mervaala of the University of Helsinki.

Researchers Susann Björk and Elina Ojala from the University of Helsinki have applied optogenetics to the evaluation of electrical signals of human heart muscle cells. The method allows measurement of and control over the electric properties of heart cells by light.

 “This method is based on ion channels known as opsins which can be activated with lasers or LED light. The genetically engineered opsins are introduced to the target cells using viral vectors. Optogenetics enables us to register the membrane potentials and calcium contents of multiple cells at once while simultaneously pacing the cells to a set contractile frequency,” Ojala explains.

Cooperating with Professor Jari Hyttinen’s group from the Tampere University of Technology, the researchers connected video microscopy to the optogenetic method, that allowed them to additionally evaluate also the contractility of the heart muscle cells.

The researchers believe that the new method based on optogenetics and the heart muscle cells derived from human induced pluripotent stem cells will significantly improve the evaluation of new drugs’ heart safety. The method may also help in diagnosis of patients with hereditary heart disorders.

Published in the journal Frontiers in Physiology, the study is part of heart regeneration research at the CardioReg group run by Professor Eero Mervaala and docent Esko Kankuri, and is conducted in cooperation with the Tampere University of Technology. The research is networked with companies, and is as such funded by Tekes.

Viite: Susann Björk, Elina Ojala &al. Evaluation of Optogenetic Electrophysiology Tools in Human Stem Cell-Derived Cardiomyocytes. Front. Physiol., 02 November 2017  https://doi.org/10.3389/fphys.2017.00884

For further information, please contact:

Researcher Elina Ojala, University of Helsinki
Tel. +358 40 743 4953
E-mail: elina.ojala@helsinki.fi

Professor Eero Mervaala, University of Helsinki
Tel. + 358 2941 25355
E-mail: eero.mervaala@helsinki.fi