Technology initiative molecular imaging (MoBiTech):

Optical QT-interval screening for cardiovascular safety tests of drugs (CordiLux)

A major hurdle in preclinical drug testing is the existing lack of suitable in vitro models that allow the prediction of potentially toxic effects in humans. The CordiLux project, coordinated by Pharmacelsus, is aimed at providing a novel in vitro model to analyze human-specific cardiotoxic drug effects as alternative to elaborate and expensive animal studies which lack sufficient predictivity. The new approach is the use of isolated cardiomyocytes to test their reactions to new potential drugs measured by optical methods. After electric stimulation, cardiomyocytes show electric activity (e.g. action potentials) reflecting the ECG of the heart muscles. These action potentials will be detected with fluorescent dyes as molecular sensors. The advantage of optical methods over current patch clamp technologies is the contact-free measurement that allows a much higher throughput, providing a very flexible screening approach, and can also be applied to very fragile cells like human cardiomyocytes.

Figure 1:Tian et al., Cell Physiol Biochem 2011; 27:281:290)

 

The aim of the project is to provide the pharmaceutical industry with a standardized, automated in vitro test system for preclinical cardiotoxicity tests that fulfills the requirements of regulatory authorities. This system may replace a significant portion of animal experiments and pivotally contribute to cardiac safety of novel pharmaceutical developments. One academic institute and seven German companies including Pharmacelsus will join their expertise in the fields of cell biology, optical imaging, soft- and hardware development and robotics to achieve this goal.

 

The CordiLux project is a collaboration of seven industrial and one academic partner:

  • arivis GmbH, Rostock
  • COTEC GmbH, Karlstein
  • CyBio AG, Jena
  • ibidi GmbH, Martinsried
  • Institute for Molecular Cell Biology, Saarland University, Homburg/Saar
  • PHAST GmbH, Homburg