Cardiotoxicity

KIC™ Arrhythmogenic Liability Screening

Classical hERG arrhythmogenic screening is error-prone because it:

  • Involves single ion channel (hERG) cell models that lack the full cardiomyocyte apparatus
  • Lacks multichannel counterbalancing (e.g., Ca2+ channel vs. hERG), and
  • Cannot detect arrhythmias based on other ion channels; cell models with other channels only partially compensate – they also lack multi-channel counterbalancing.

Cardiosafety efforts then suffer by:

  • Unnecessary waste of resources during drug development, and
  • Allowing arrhythmogenic compounds into clinical trials, and worse yet, onto the market

Vala Sciences’ KIC arrhythmogenic liability screening:

  • Eliminates the false positives and negatives of hERG testing by

    • Imaging live cardiomyocytes (human stem cell-derived and animal sources) and
    • Performing single-cell KIC of 100s of cells to eliminate the action potential propagation “blur” of whole-well imaging and create unmatched statistical robustness;
  • Utilizes intracellular Ca++ transients based on the full set of cardiac ion channels,
  • Provides timely results on 100s of compounds per order in early in drug discovery,
  • Measures the Ca++ transient as surrogate for QT prolongation/shortening,
  • Provides label and parameter multiplexing to assess multiple endpoints, all of which contribute to
  • Accurately identify pro-arrhythmic compounds early in drug discovery

Vala Sciences has completed validation studies on over 150 compounds. Please contact Vala for further information including presentation of our validation studies, and to discuss contract arrhythmogenic liability screening.

 

 

 

References:

1. Cardiomyocyte image segmentation, adapted from F. Cerignoli et al., J Pharm Tox Meth, 66: 246–256, 2012.

2. Action potential, calcium transient & contractile motion, D. Bers, Nature 415:198-205, 2002.

3. Cardiac action potential and ion currents, adapted from M. Hoekstra et al.,  Front Physiol. 3:346, 2012.

4. Progression of normal to long QT to EAD to Torsade de Pointes, adapted from F. Campbell et al., Aust Vet J. 80(10):611-6, 2002.