Title
Drug repositioning for idiopathic epilepsy using gene expression signature data
Authors
Pawan Kumar, Deepak Sheokand, Annu Grewal, Vandana Saini & Ajit Kumar*
Affiliation
Toxicology and Computational Biology Group, Centre for Bioinformatics, Maharshi Dayanand University, Rohtak, Haryana, 124001; *Corresponding author:
Ajit Kumar – E-mail: akumar.cbt.mdu@gmail.com; ajitkumar.cbinfo@mdurohtak.ac.in
Vandana Saini – E-mail: vandana.rs.bioinfo@mdurohtak.ac.in; vandanas64@gmail.com
Pawan Kumar – E-mail: pawan.rs.bioinfo@mdurohtak.ac.in
Deepak Sheokand – E-mail: deepak.rs.bioinfo@mdurohtak.ac.in
Annu Grewal – E-mail: annu.rs.bioinfo@mdurohtak.ac.in
Article Type
Research Article
Date
Received September 2, 2022; Revised October 6, 2022; Accepted October 6, 2022, Published October 31, 2022
Abstract
Epilepsy is one of the most common neurological disorders, affecting millions of patients with a substantial economic and human burden. About 30-40% of epileptic patients remain un-treated after the therapeutic option. Genetic or idiopathic epilepsy count about 40% of total epilepsy patients, showing a maximum percentage for drug-resistant epilepsy. Since the last century basic approach to understanding disease progression and drug discovery has been through the prism, exploring all possible causes and treatment options. Here we report about the gene expression-based drug repositioning study for epilepsy. Epilepsy gene expression data was retrieved from the Gene Expression Omnibus database, while drugs-associated gene expression data was retrieved from the Connectivity map (CMAP). The study predicted309 drug compounds which can alter genetic epilepsy-mediated gene signature using an in-house developed R-script. These compounds were docked against identified epilepsy targets– Voltage-gated sodium channel subunit a2 (Nav1.2); GABA receptor a1-b1; and Voltage-gated calcium channel a1G (Cav3.1)using Carbamazepine, Clonazepam, and Pregabalin as standard drugs, respectively. Twenty-one predicted drug compounds showed better binding affinity than respective standards against the selected epileptic receptors. Among these drug compounds, Ergocalciferol, Oxaprozin, Flunarizine, Triprolidine and Cyproheptadine have been previously reported for anti-epileptic activities and can be potential hits to target idiopathic epilepsy.
Keywords
Gene-expression study, Gene expression omnibus, Connectivity map, Voltage-gated calcium channel, GABA receptor, Molecular docking study, homology modelling
Citation
Kumar et al. Bioinformation 18(10): 845-852 (2022)
Edited by
P Kangueane
ISSN
0973-2063
Publisher
License
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
