Cardiotoxicity testing

Understanding cardiac risk and novel therapies

Fraunhofer ITEM aims to protect man from health hazards and to contribute to the development of novel therapeutic approaches. With our additional specialization on cardiovascular research, we offer customized setups: 

  • Target identification
  • OMICs analytics
  • Small-molecule analytics
  • Nanoparticle drug delivery
  • Cardiac toxicology in vitro and ex vivo
  • Efficacy testing in vitro and ex vivo
  • Early-phase clinical trials

Small-molecule analytics

© Fraunhofer ITEM, Ralf Mohr

Microscale thermophoresis (MST) describes a process in which molecules undergo directional movement due to a temperature gradient. It can be utilized for highly sensitive interaction studies of fluorescently labeled, e.g. RNA-based therapeutics at a microliter scale, regardless of their size or chemical composition. 

Thus, MST is significantly superior to isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) in terms of sample volume consumption or experimental setup, as it also does not require immobilization of an interaction partner. MST can be used to investigate various RNA/DNA/proteins for their binding capacities towards potential target structures in a preclinical setting. In this way, binary and ternary interactions can be assessed and analyzed for future RNA drug candidates being identified early on and in a cost-efficient manner. 

Analysis of cardiotoxicity in vitro: xCELLigence RTCA Cardio ECR

Adverse effects of drugs, such as cardiotoxicity, are a major concern in pharmaceutical development and a major cause of drug withdrawal from the market. The xCELLigence RTCA Cardio ECR operates label-free and non-invasively to detect the effects on 2D human cardiac function in real time, allowing validation of cardiotoxicity in an early stage of drug discovery.

  • Measuring impedance and field potential to determine viability and contractility (ECR) of beating cells 
  • Monitoring (drug-induced) effects from minutes to weeks
  • iPSC-derived/primary cardiomyocytes
  • Sources and models: iPSC-derived/primary cardiomyocytes, disease modeling, co-culture approaches
  • Drug testing of known and unknown compounds 
  • Testing of siRNA, modRNA, lncRNA etc.
  • Ion/non-ion channel modulators
  • In-house available, compatible downstream assays like RNA/protein/OMICS analyses, fluorescence-based imaging, molecular read-outs 

Analysis of cardiotoxicity ex vivo: living myocardial slices

Bridging the gap from basic research to mid-stage development is key in translational research, especially in cardiac model systems. We offer cardiac model systems that utilize a 3D platform of living myocardial slices (LMS) derived from cardiac tissues (human, rodent, pig). Multicellular preparations are cultivated under physiological conditions covering mechanical and electrical stimulation (MyoDish system). Miniaturized LMS allow high-throughput formats.

  • Compound testing
  • Monitoring electrophysiology (e.g. rhythm, conduction, contractility, relaxation time)
  • In-house available, compatible read-outs like viability and toxicity tests, RNA/protein/OMICS analyses (fluorescence-based imaging combined with tissue clearing) 
  • Disease modeling (chemical and mechanical)
  • Biomarker discovery
© Fraunhofer ITEM, Ralf Mohr

Contact

Jan  Fiedler

Contact Press / Media

Priv.-Doz. Dr. Jan Fiedler

Manager of the Working Group on Molecular Biomarkers for Disease Modeling

Phone +49 511 5350-755