Testing drugs with light

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A three-dimensional partial reconstruction of an adult heart muscle cell that has been dyed with an optical sensor. Visible here are the complex, network-like structures of cell membrane indentations. The optical signals created in these indentations are measured at CordiLux. Source: UdS

11.10.2011  - 

If an already approved drug is withdrawn from the market, it is frequently because of damaging effects on the heart. Togetherwith industry partners, the CordiLux project at the University of Saarland has developed a biotechnological process that can comprehensively test the side effects of drugs on heart cells. The three-year project has a funding volume of 4 million euros, 2.5 million euros of which stems from the Federal Ministry of Education and Research (BMBF). 550,000 euros has been pledged to the medical faculty of the University of Saarland (Saarland University).

Among drug developers, impairment of the heart is high on the list of side effects that must be avoided in any case. Researchers test the electrical activity of the heart in the hope of excluding this outcome. “To date, these tests have focused primarily on a single protein molecule that influences the electrical activity of the heart,” explains Peter Lipp, Director of the Institute for molecular cell biology at the University of Saarland. “These tests are already very exact, but they focus only on one small aspect, and can thus provide only a partial insight.” As a result, the corresponding long-term side effects occur have repeatedly led to compounds being removed from the market after years of sale. This new procedure, however, illuminates the cell as a whole. Translated, Cordilux means ‘heart light’.

This enables the measurement not only of the electrical activity of the entire cell, but also of how these signals are changed after the addition of other substances. “Electrical activity in the cell has measurable for decades”, acknowledges Lipp. However, the classic ‘patch clamp technique’ is costly, and is not suited to large-scale projects, criticises Kästner. “After one day, you might have investigated around a dozen and a half cells.” He and his colleagues have thus modified and combined the technology with other methods, so that it can be applied to fully-developed heart muscle cells.” To do this, they are using fluorescence microscopy, a non-contact optical technique. An automated microscope can take up to a thousand frames per second – this fine resolution is important if the change in cell activity is to be mapped exactly over a period of time.

Similar to an ECG

To visualise the electrical signals in the cells, they are coloured with a dye whose optical properties change with the changing electrical activity in the cell. Finding a suitable dye is part of the research, stresses Lipp: “We use mostly organic molecules.” One alternative and promising method is to modify the cells so that they produce the dye themselves in the form of proteins.“ In this way, the cells are coloured and the signal measured; the potential substance is then administered and the changes in the optical signal are measured as a visible indicator of electrical activity in the cell.” “You could compare it to ECG,” says Lipp “The signals can have a different wavelength after the drug is administered”. 

To evaluate the signals, as well as to automate the process, cultivate and to study the cells, the UdS is collaborating with a consortium of seven companies, among them CyBio, a subsidiary of Jena GmbH, as well as and Parascelsus GmbH. The partners bring know-how in certification and in the creation of an industrially deployable device. By the end of the project in June 2014, Lipp and Kästner hope to work together with the network to develop a demonstrator that will serve as a model for an industrial prototype. “In principle, we research up to the point where industrial development begins and then pass it to the companies,” says Kästner. “We want to make the process available as a service, and on the other hand provide the groundwork for corresponding product development.” After all, we don’t do the research only for ourselves here in the lab. In the end, it has to be a test that people actually use.”

 © biotechnologie.de/ck