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Cardio.Plex

Ncardia’s Cardio.Plex Services provides a multiparametric analysis to investigate potential cardiotoxicity of test compounds over a relatively long time span. A combination of functional and structural toxicity analysis in fully functional and validated hiPSC-derived cardiomyocytes after compound treatment forms the basis of this service.

As complex mechanisms underlie drug-induced toxicity, some compound effects will only become evident after longer incubation times. Therefore, this service includes an analysis up to 48 hours after incubation. Efficient cardiac safety assessment should analyse structural and functional toxicity. Cardio.Plex allows functional toxicity analysis by a combination of electrophysiology and impedance monitoring of hiPSC-derived cardiomyocytes. The structural toxicity is defined by the detection of Troponin I (a clinically relevant and established diagnostic marker for myocardial damage) release after compound addition. The Cardio.Plex Service offers the most extensive evaluation of cardiotoxicity available and reduces the risk of missing any cardiotoxic effect of candidate drugs.

Service specifications

Cell type

Human iPSC-derived cardiomyocytes

Service type

Electrophysiology and impedance functional analysis + Troponin I release analysis

Format

2 x 48 wells

Time points

Electrophysiology temporal study (0, 0.5, 1, 2, 8, 24 and 48 hours after compound addition)

Troponin I release (16, 24, 40 and 48 hours after compound addition)

Compound concentrations*

0.1, 1, 10 µM in medium + 0.1% DMSO (in triplicates)

Positive controls

L-type Ca2+ channel blocker: Nifedipine

hERG channel blocker: Dofetilide

Ponatinib (as positive control for Troponin I release)

Vehicle control

0.1% DMSO

Parameters

Electrophysiology: beat rate, beat rate coefficient of variance (CoV), field potential duration (FPD), depolarization peak amplitude, proarrhythmic events

Contractility: impedance amplitude and peak width

Troponin I release

Timelines

5 weeks (for up to 8 compounds)

Deliverable

A study protocol will be agreed before study initiation. Results will be presented in a final study report.

*Suggested concentrations, to be agreed with client