Authors :
Presenting Author: Hyo Jeong Kim, MD, PhD – Gachon University College of Medicine
Song Ee Youn, MD – Kyung Hee University School of Medicine
Jihun Kim, PhD – Severance Children’s Hospital, Yonsei University College of Medicine
Hoon-Chul Kang, MD-PhD – Severance Children's Hospital, Yonsei University College of Medicine
Rationale:
We compared the effects of phenytoin, which primarily targets fast-inactivating sodium channels, and lacosamide, which selectively targets slow-inactivating sodium channels, on neuronal activity using iPSCs derived from a patient with SCN8A -developmental and epileptic encephalopathy (DEE).
Methods:
iPSCs were derived from a male patient with epilepsy characterized by myoclonic atonic seizures (SCN8A, c.4871T >G, p.Ile1624Ser, heterozygous, de novo). Drug testing was conducted on neurons that were 6 weeks old. Neuronal electrophysiological effects were recorded and analyzed using a multi-electrode array system.
Results:
Drug testing was conducted when the neurons were 6 weeks old. Phenytoin exhibited rapid effects within 10 minutes of treatment. Lacosamide also showed effectiveness after 10 minutes, but as previously reported, its effects were more pronounced after one hour. The main data, based on spike levels and mean firing rates, showed no significant changes at a 1 µM concentration. However, a trend of decreasing spike levels over time was observed after lacosamide treatment. When analyzing synchrony data, a noticeable difference was observed with phenytoin at higher concentrations, while lacosamide's effects became evident only over time. In conclusion, the efficacy of both drugs is clear. Although lacosamide acts more slowly, its effectiveness was confirmed.
Conclusions:
Both phenytoin and lacosamide were effective in treating SCN8A-DEE. Due to the differences in the time-dependent effects on spike onset between these two antiseizure medications, phenytoin and lacosamide could be used as monotherapy or in combination therapy based on their distinct mechanisms of action.
Funding: No