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Established in , with previous co-organisers including Neusentis, Medimmune and BioFocus, this afternoon session of ion channel focused presentations provides an opportunity for delegates to participate in networking, present a poster and listen to presentations from respected ion channel researchers. A recurring theme throughout the event was the importance of automated patch clamp APC electrophysiology in support of the optimisation of small molecules, biologics and in the early cardiac safety profiling of selected compound series. This research being founded on the observation that specific deletion of HCN2 in nociceptive neurons leads to reduced neuropathic and inflammatory pain sensation, without effects on normal sensation of acute pain. Peter outlined the evolution of his project to develop potent and selective HCN2 blockers for therapeutic use in the clinic, with a key project objective of minimising block of HCN4 channels in the heart. Peter also touched upon his research into tinnitus, via a collaboration with Mark Wallace and Deborah Hall from the University of Nottingham. The hypothesis behind this work being that tinnitus may be reduced by use of HCN2 blockers to reduce the abnormally high firing in unmyelinated auditory nerve fibres. Matt Bridgland-Taylor then presented a case study combining electrophysiology with intracellular concentration analysis to assess the hERG liability of small molecules. In addition to assessing any link between the intracellular concentration and the kinetic profile of block, this also allowed to verify that the hERG inactive compounds were accessing the CHO cells used in the electrophysiology assay. This approach offers the potential for retaining the ion channel blocking activity of the knottin, whilst gaining an extended half-life and additional specificity conferred by multiple contact surfaces of the antibody. Damian presented proof of concept data where phage display was used to engineer specificity into both antibody and peptide, with QPatch electrophysiology data presented for both K v 1. Skeletal muscle channelopathies was the topic of choice for Roope Mannikko from University College London , who discussed myotonia and periodic paralysis and the effect of Na v 1. The programme has identified nM potency blockers with good gene family but no species selectivity issues, strong efficacy in native human T-cell assays, and superior drug-like properties compared to leading preclinical small molecules and biologics such as ShK Dalazatide, Kineta Therapeutics. The next Metrion Biosciences hosted event will be on 11 th July Review written by the Editor. Previous Post Next Post.

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