The cardiac late Na+ current (late INa) generates persistent inward currents throughout the plateau phase of the ventricular action potential and is an important determinant of repolarisation rate, EADs and arrythmia risk¹. As inhibition of late INa can offset drug effects on hERG and other repolarising K⁺conductances, it is one of the key cardiac channels in the Comprehensive in vitro Pro-arrythmia Assay (CiPA) panel being developed by the FDA to improve human clinical arrythmia risk assessment²̛ ³.

Cardiac toxicity remains the leading cause of new drug safety side-effects. Current preclinical cardiac safety assays rely on in vitro cell-based ion channel assays and ex vivo and in vivo animal models⁽¹⁾. These assays provide an indication of acute risk but they do not always predict the effect of chronic compound exposure, as recently seen with oncology drugs. Therefore, new assays are required to characterise chronic structural and functional effects in human cells earlier in drug discovery. Impedance-based technology can provide more accurate chronic cardiotoxicity measurements in an efficient manner using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

By accurately defining the drug exposure levels that affect QRS duration, researchers can establish safety margins, prioritise lower-risk compounds, and reduce the chance of late-stage failures due to cardiac toxicity

We demonstrate the generation and validation of a stable CHO-hHCN2 cell line used as a cellular tool in the successful development of hHCN2 automated electrophysiology screening assays.

Metrion and Sophion collaborated to determine whether other insoluble salts can act as seal enhancers, or whether this property is unique to CaF2.

CiPA logoThe International Council on Harmonization (ICH) S7B and E14 regulatory guidelines were introduced in 2005 to evaluate the proarrhythmic liability of new drugs.

Academic case study on Nav1.9 as a drug target by Associate Professor David Bulmer (University of Cambridge). Overview of Metrion’s newly developed Nav1.9 screening assays by Metrion CSO, Dr. Eddy Stevens.

Alex Haworth, Senior Scientist at Metrion, introduces a poster demonstrating Metrion's development of a monoclonal CHO cell line expressing hNav1.9, validated via manual and automated patch clamp techniques.

Introduction to ion channel screening at Metrion

Introduction to neuroscience at Metrion