Metrion is working towards the requirements of the FDA’s Comprehensive in vitro Proarrhythmia (CiPA) initiative (cipaproject.org) which comprises 3 parts: 1) High quality in vitro cardiac ion channel assays, 2) Comprehensive in silico action potential (AP) models, and 3) Predictive assays using induced pluripotent stem cell derived cardiomyocytes (iPSC-CM).
We are building upon our panel of in vitro human cardiac ion channel assays and applying the data to various in silico cardiac models, and more recently assessing commercially available iPSC-CM for use in phenotypic assays to assess the pharmacological and risk predictions from our in vitro and in silico cardiac safety data.
Here we outline our progress in validating and implementing all 3 pillars of the CiPA regime by building upon work presented previously at the 2015 SPS meeting in Prague.
The presence of sensory neuron markers, excitability properties consistent with sensory neurons, and evidence of nociceptor ion channels (using both RNASeq and electrophysiology) provides strong evidence that iCell Sensory Neurons have a robust sensory neuron phenotype suitable for supporting pain discovery programs.
Using automated patch clamp technology, we evaluate the potency and selectivity of ten Nav1.7-selective arachnid peptide toxins, which have been fused to the C-terminus (Fc region) of human IgG1.