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Cardio.Acute

Ncardia’s in-house Cardio.Acute Service provides acute cardiac safety profiles of test compounds based on the electrophysiology of fully functional human cardiomyocytes in the validated Ncyte CardioPlate™ Maestro MEA 96.

Investigating the electrical activity of human induced pluripotent stem cell-derived cardiomycoytes (hiPSC-CMs) and their acute response to drugs is part of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, which aims to refine current ICH guidelines to predict clinical potential for life threatening Torsade de Pointes (TdP) tachyarrhythmia.

Our Cardio.Acute Service uses pre-plated cardiomyocytes in the Ncyte CardioPlate™ Maestro MEA 96. This ready-to-use CardioPlate™ is manufactured at our ISO-certified manufacturing site and guarantees a fully quality controlled assay plate with high plate-to-plate reproducibility. Together with the Maestro MEA platform it provides a highly relevant and predictive in vitro assay to study compounds’ cardiac safety profile in drug development. This service is running at Ncardia on a biweekly basis – Simply reserve a spot for your test compounds on the next Cardio.Acute assay plate.

*CiPA (Comprehensive in Vitro Proarrhythmia Assay) is a project driven by the Health and Environmental Science Institute (HESI) and the FDA.

Workflow

Service specifications

Cell type

Ncardia human iPSC-derived cardiomyocytes (ventricular-like)

Assay plate

Ncyte CardioPlate Maestro MEA 96

Instrument Maestro MEA (Axion BioSystems)

Time points

0, 30 Minute compound exposure

Compound concentrations

3 concentrations as defined by the client

Replicates

4

Positive controls

hERG channel blocker: Dofetilide

β-adrenergic receptor agonist: Isoproterenol

Vehicle control

0.1% DMSO

Parameters

Beat rate, beat period coefficient of variance (CoV), field potential duration (FPD), depolarization peak amplitude and (pro)arrhythmic events

Timelines

2-3 weeks (upon compound submission)

Deliverable

Results are sent as final study report.

 

Service data

CiPA-like study using Cardio.Acute

For the CiPA-like Cardio.Acute service, an Ncyte CardioPlate™ Maestro 96 was shipped from our manufacturing site to our services site. Baseline recordings are taken and compounds are applied in single dose. Compound effects are assessed from recordings taken 30 min after incubation. Table 1 summarizes the effects of a selection of CiPA reference compounds that were tested in a blinded fashion during the CiPA phase II validation study. Compounds from the high risk group revealed pro-arrhythmic events at Cmax concentrations or higher, and thus correctly classify high risk compounds.