Understanding cardiac safety early is critical in drug development. In their latest poster, Jazz Pharmaceuticals, explain how they utilised Metrion’s clinically translatable cardiotoxicity assay to do exactly that.
The TTX-resistant sodium channel Nav1.8 is expressed in peripheral sensory nociceptors and is implicated in a range of inflammatory and visceral pain conditions such as irritable bowel syndrome (IBS)1. Nav1.8 channel function in sensory neurons changes after injury or inflammation, with a redistribution from the soma to axons and upregulated activity through inflammatory mediators and signalling pathways. This is thought to underlie increased neuronal excitability and a greater role of Nav1.8 currents in persistent, repetitive and ectopic action potential firing in inflammatory and visceral pain. Several gain-of-function mutations in Nav1.8 have also been detected in human patients suffering from small fibre neuropathy (SFN), offering similar genetic target validation and clinical population for personalised medicine approaches seen with Nav1.7 mutations in primary erythmelalgia, paroxysmal extreme pain and SFN patients.
Understanding cardiac safety early is critical in drug development. In their latest poster, Jazz Pharmaceuticals, explain how they utilised Metrion’s clinically translatable cardiotoxicity assay to do exactly that.
Development of a robust hNaV1.9 high-throughput screening assay on the Sophion Qube384 platform. This is complemented by a suite of ion channel selectivity assays and sensory neuron recordings to create a versatile screening cascade to support NaV1.9 drug discovery programmes.