Abstract

Neurons from Human Stem Cells in 2D and 3D Culture for the Discovery of New Antiseizure Agents

Robert Halliwell, Professor in the School of Pharmacy and the School of Dentistry, University of The Pacific

Somatic tissues derived from human stem cells offer significant advantages over animal models for drug studies and disease modeling. For over 20 years, my lab has been addressing the neuropharmacological and neurophysiological properties of human stem cell derived neurons in 2D and, more recently, in 3D culture. This presentation will cover the challenges and advantages in combining stem cell created neuroglial cells, maintained in ultra-long-term culture, with multi-electrode array technology, to advance the discovery of novel antiseizure agents for epilepsy. Specifically, I will present recent data demonstrating that human neuroglia cell networks are able to detect the antiseizure properties of diverse antiepileptic drugs with high sensitivity, specificity and reliability. I will also present one of our recent studies showing that fenamates, a well-established class of NSAID, that are also subunit-selective potentiators of the GABAA receptor (the major inhibitory receptor in the brain) have potent antiseizure properties. These observations provide new evidence for a novel therapeutic approach to the treatment of epilepsy, and we are exploring these well-established NSAIDs for drug repurposing. Overall, our data, and that emerging from other labs, demonstrate the power of stem cell derived neural circuits, supported by glia to identify new and novel agents for complex, difficult-to-treat, neuropsychiatric disorders.