Seizure Liability: New Approaches to Detection (S04)

Symposium Chair(s)

• Simon Authier, DVM, MBA, PhD, DSP

  Principal Director
  Charles River Laboratories
  Laval, Quebec, Canada

• Ruth Roberts, PhD, ERT, FBTS, ATS, FRSB, FRCPath

  Director and Cofounder
  ApconiX
  Macclesfield, England, United Kingdom

Symposium Speaker(s)

• Jennifer Cohen, PhD, DABT

  Director
  Drug Safety Research and Evaluation
  Takeda Development Center Americas
  San Diego, California, United States

• Jennifer Pierson, MPH

  Associate Director
  HESI
  Washington, District of Columbia, United States

• Dan Mellon, PhD

  Deputy Director
  Division of Pharmacology/Toxicology for Neuroscience
  US FDA
  Washington, District of Columbia, United States

Educational Co-Support Provided by: Charles River and DSI

Seizure liability remains a significant cause of attrition in drug discovery and development, leading to loss of competitiveness, delays, and increased costs. Current detection methods rely on observations made in in vivo studies intended to support clinical trials, such as tremors or other abnormal movements, followed up with a nonclinical EEG study. Thus, it would be preferable to have earlier prediction of seizurogenic risk that could be used to eliminate liabilities early in discovery while there are options for medicinal chemists making potential new drugs. Attrition due to cardiac adverse events has benefited from routine early screening; could we reduce attrition due to seizure using a similar approach? Specifically, microelectrode arrays (MEA) could be used to detect potential seizurogenic signals in stem-cell-derived neurons. In addition, there is clear evidence implicating neuronal voltage-gated and ligand-gated ion channels, GPCRs and transporters in seizure. Recent data provide evidence that we can detect seizure in MEA in linked to a panel of ion channel assays that predict seizure, with the aim of influencing structure activity relationship at the design stage and eliminating compounds predicted to be associated with pro-seizurogenic state. This session will be of great interest to attendees looking to have a better understanding of cutting-edge science in MEA and ion channel and how to apply these to identify and to mitigate seizure risk.

Presentations:

• 2:00 PM - 2:25 PM CT

  Seizure Liability and Premonitory Sign Incidence: Opportunities and Pitfalls with Standalone EEG Studies or When EEG is Included in Repeat Dose Toxicology
  

  Symposium Speaker: Simon Authier, DVM, MBA, PhD, DSP – Charles River Laboratories
• 2:25 PM - 2:50 PM CT

  In Vitro Human Ion Channel Assays Predictive of Drug Induced Seizure
  

  Symposium Speaker: Jennifer Cohen, PhD, DABT – Takeda Development Center Americas
• 2:50 PM - 3:15 PM CT

  Predicting Seizure Using Cell-Based Microelectrode Arrays: A HESI Consortium Study
  

  Symposium Speaker: Jennifer Pierson, MPH – HESI
• 3:15 PM - 3:45 PM CT

  Break
• 3:45 PM - 4:10 PM CT

  Regulatory Challenges of Seizures in Toxicology Studies: Utility of Alternative Models in Regulatory Decision Making
  

  Symposium Speaker: Dan Mellon, PhD – US FDA
• 4:10 PM - 4:35 PM CT

  An Integrated Approach for Early In Vitro Seizure Prediction Utilizing Human Derived Induced Pluripotent Stem Cells and Human Ion Channel Assays
  

  Symposium Speaker: Ruth A. Roberts, PhD, ERT, FBTS, ATS, FRSB, FRCPath – ApconiX
• 4:35 PM - 5:00 PM CT

  Panel Discussion