MAY 25, 2016 8:00 AM PDT

Novel applications of automated electrophysiology in ion channel drug discovery

  • Research Scientist, Eurofins Panlabs
      Dr. David Wei is a research scientist leading the ion channel services group at Eurofins Panlabs, where he serves as a principal investigator for oversight of ion channel drug discovery and safety assessment projects and client contact, and advice on discovery and safety programs that included over 60 ion channel targets for more than 300 clients in industry and academia. Prior to joining Eurofins, David worked at other life science companies including EMD Millipore and Targacept, where he designed and developed the first novel high-throughput in vitro slice electrophysiology recording system in support of drug discovery and toxicology programs. He has also implemented numerous screening assays using automated patch clamp systems such as IonWorks Barracuda, IonWorks® Quattro, IonFlux™ HT, QPatch and PatchXpress 7000A Systems in support of ion channel drug discovery and safety programs.
      David received a Ph.D. degree from University of Louisville, Kentucky. After his Ph.D., David held a postdoc position at the University of Louisville; he co-authored numerous research articles published in top peer-reviewed journals.
    • Principal Research Scientist, Eli Lilly and Company
        Dr. Rok Cerne is a Principal Research Scientist at Eli Lilly and Company, where he supports drug discovery projects with ion channel assays and expertise. Prior to Eli Lilly, Rok was at RedpointBio, where he focused on discovery of novel TRP channel modulators and at Purdue Pharma, where he supported the discovery of novel pain therapeutics. At Purdue, his group was among the first to introduce automated electrophysiology, which gave him the opportunity to contribute to software development for the PatchXpress® System. As a consultant, he continued to maintain involvement with technology development projects such as the IonWorks Barracuda® System.

        Rok received a MD from University of Ljubljana, Slovenia and a Ph.D. from Iowa State University. After his Ph.D., Rok held a postdoc position at the University of Washington followed by a research faculty position at Duke University. His academic research employed electrophysiological and imaging techniques to study pain and epilepsy.

      DATE:  May 25, 2016
      TIME:  8am Pacific time, 11am Eastern time, 4pm UK time, 5pm European time, 11pm Beijing time

      In this two-part webinar, we will be presenting the following topics in ion channel drug discovery.

      Topic 1: Novel high-throughput approach to evaluate state dependence and selectivity of voltage-gated ion channels

      Speaker: Rok Cerne, Ph.D, Principal Research Scientist, Eli Lilly and Company

      Voltage-gated ion channels represent important drug targets. Current drug discovery efforts targeting ion channels often focus on identifying state -dependent inhibitors, and these characterizations are traditionally done using manual patch-clamp methods. Automated electrophysiology assays were introduced to increase the throughput of electrophysiological profiling, however these assays typically relay on pulse based protocols where compound potency is affected by the mechanism of channel gating and the kinetics of compound binding.
      In this webinar, a novel high-throughput approach is presented using automated electrophysiology. This assay allowed for robust assessment of state-dependent effects of test agents and enabled direct comparison of compound potency across several ion channel subtypes at equivalent levels of inactivation. In addition to determination of state dependency and selectivity, the assay provided valuable information on the kinetics of compound association and dissociation. 

      Learning Objectives:
      • Learn about  continuous holding of membrane potential on a high throughput automated electrophysiology instrument
      • Learn about measurement of compound effects across several ion channel subtypes at equivalent level of inactivation
      Topic 2: Validating cardiac ion channels using automated electrophysiology for the CiPA paradigm

      Speaker: Haiyang (David) Wei, Ph.D, Team Lead Scientist, Eurofins Pharma Discovery Services

      Drug-induced QT interval prolongation and Torsades de Pointes (TdP) arrhythmia are the leading causes for drug withdrawal from the market. For the past decade, in vitro hERG channel assays and in vivo QT measurements have been conducted as surrogates for proarrhythmic risk propensity according to ICH S7B and ICH E14 guidelines. This paradigm, although effective, suffered from lack of specificity and led to unnecessary compound attrition during drug development. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) is a new cardiac safety testing paradigm intended to address this limitation with improved prediction of drug’s proarrhythmic liability. This new paradigm includes a panel of in vitro assays that integrates effects of the test compounds on several cardiac ion channels.
      In this study, three cardiac ionic currents (IKr, ICa, INa, fast) were validated on a novel microfluidic-based automated patch clamp system to evaluate accuracy, precision and robustness of the assays. The results demonstrate suitability of the system for high throughput screening of drug effects on cardiac ionic currents, and provide data for in silico reconstructions in the CiPA paradigm for defining proarrhythmic risk.

      Learning Objectives:
      • Learn about the in vitro assay panel on cardiac ion channels relating to the CiPA paradigm
      • Learn about the application of automated patch clamp in assessing cardiac ionic currents

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