Identification of New <scp>KCNT1</scp> ‐Epilepsy Drugs by <i>In Silico</i> , Cell, and <i>Drosophila</i> Modeling
This study identified a known drug, antrafenine, that reduces KCNT1 channel activity, reduces seizure activity in Drosophila, and crosses the blood-brain barrier in the mouse, suggesting its potential applicability as a new treatment for KCNT1 epilepsy. The sequential in silico, in vitro, and in vivo mechanism-based drug selection strategy used here may have broader application for other human disorders where a disease mechanism has been identified. ANN NEUROL 2025;98:1261-1274.
Authors
- Bethan A. Cole (ORCID: https://orcid.org/0000-0002-6214-016X)
- Jonathan D. Lippiat (ORCID: https://orcid.org/0000-0003-3748-7345)
- Michael G. Ricos (ORCID: https://orcid.org/0000-0002-1860-4692)
- Katie J. Simmons (ORCID: https://orcid.org/0000-0003-4846-9097)
- Zeeshan Shaukat
- Nadia Pilati (ORCID: https://orcid.org/0000-0002-1525-333X)
- Grigori Y. Rychkov (ORCID: https://orcid.org/0000-0002-2788-2977)
- Leanne M. Dibbens
- Stephen P. Muench (ORCID: https://orcid.org/0000-0001-6869-4414)
- Rashid Hussain
Institutions
- University of Leeds (GB)
- University of South Australia (AU)
- South Australian Health and Medical Research Institute (AU)
- Città della Speranza Foundation (IT)
- The University of Adelaide (AU)
Publication Details
- Journal
- Annals of Neurology
- Published
- 2025-09-13
- DOI
- https://doi.org/10.1002/ana.78031
- Primary Topic
- Ion channel regulation and function
- Type
- article
- Field-Weighted Citation Impact
- 0.00