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Updated: Jan 17, 2026
Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients
Published on: December 18, 2016
Transcriptomic profiling unveils novel therapeutic options for drug-resistant temporal lobe epilepsy
Patricia Sánchez-Jiménez1, Lola Alonso-Guirado2, Laura Cerrada-Gálvez3
1Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigaciones Sanitarias la Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain; NIMGenetics Genómica y Medicina S.L., Madrid, Spain.
Background:
Epilepsy drug treatments fail in 25-30 % of patients, leading to drug resistance. Temporal lobe epilepsy is the most prevalent subtype associated with drug resistance. Classical drug discovery is a long and extremely costly process with a high failure rate in clinical trials. Drug repurposing is a more cost- and time-effective strategy. Hence, the main objective of this study is to propose drug candidates for the treatment of drug-resistant temporal lobe epilepsy (DR-TLE) through drug repurposing based on transcriptomic profiling.
Methods:
Total RNA-sequencing (RNA-Seq) was performed on 45 formalin-fixed paraffin-embedded (FFPE) hippocampi of DR-TLE patients and 36 FFPE hippocampi of post-mortem biobank donors. RNA-Seq was carried out on an Illumina NovaSeq 6000 platform in 100bp paired-end. Drug repurposing based on transcriptomic analysis top candidates was performed against these databases: Pandrugs2, PharmOmics, DGIdb, ToppGene, L1000CDS2 and Connectivity Map.
Results:
We identified 887 genes differentially expressed between DR-TLE patients and post-mortem controls. We observed 74 potential drug candidates in at least two independent databases. Of these, we selected only the 11 which can cross the blood-brain barrier: cobimetinib, panobinostat, melphalan, rucaparib, alectinib, ponatinib, danazol, carboplatin, vandetanib, erlotinib, and gefitinib. After analyzing their mechanisms to modulate epileptogenesis, their safety and efficacy profiles from previous publications, we provide a list of the top 5 candidates.
Conclusion:
Based on differential RNA-Seq profiling, we therefore propose erlotinib, danazol, rucaparib, ponatinib, and panobinostat.
