Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Ensuring the safety of drugs for patients with specific neurological disorders is of utmost importance. For instance, certain antiepileptic drugs (AED) are contraindicated for use in individuals with Dravet Syndrome (DS), a condition characterized by impaired Na+ channel function. Developing in vitro assessment methods capable of detecting adverse drug reactions and drug effects on neurons derived from DS patients holds great promise for drug safety evaluation and therapeutic advancement. In this study, microelectrode array (MEA) measurements combined with low-frequency analysis were utilized to examine AED responses in human induced pluripotent stem cell derived DS organoids. Exposure to contraindicated drugs such as carbamazepine and phenytoin resulted in an increase in network oscillations in DS organoids while maintaining oscillation intensity. Additionally, carbamazepine administration seemed to elicit activities beyond mere oscillations, partially aligning with observations from the DS mouse model. Conversely, treatment with the therapeutic drug sodium valproate led to a similar reduction in activity in both healthy and DS organoids. The frequency characteristics of spontaneous firing and AED responsiveness in DS organoids exhibited a partial correlation with typical electroencephalography patterns observed in vivo. In conclusion, this study unveiled adverse drug responses and disease-specific functional traits in DS organoids, demonstrating effectiveness for DS patient safety assessment, precision medicine, and antiepileptic drug screening.
