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A systems-level framework for anti-epilepsy drug discovery
File | Description | Size | Format | ||
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MAIN TEXT_REVISED.docx | Accepted version | 123.53 kB | Microsoft Word | View/Open | |
Figure 1.pptx | Supporting information | 122.96 kB | Microsoft Powerpoint XML | View/Open | |
Title: | A systems-level framework for anti-epilepsy drug discovery |
Authors: | Johnson, MR Kaminski, RM |
Item Type: | Journal Article |
Abstract: | Modern anti-seizure drug development yielded benefits in terms of improved pharmacokinetics, safety and tolerability profiles, but offered no advances in efficacy compared to previous older generations of anti-seizure drugs. Despite significant advances in our understanding of the genetic bases to epilepsy, and a welcome renewed interest on the severe monogenic epilepsies, modern genetics has yet to directly inform more effective or disease-modifying anti-seizure drugs. Here, we describe a new approach to the identification of novel disease modifying anti-epilepsy drugs. The systems genetics approach aims to first identify pathophysiological mechanisms by integrating polygenic risk with cellular gene expression profiles and then to relate these molecular mechanisms to druggable targets using a gene regulatory (regulome) framework. The approach offers an exciting and flexible framework for future drug discovery in epilepsy, and is applicable to any disease for which appropriate cell-type and disease-context specific data exist. |
Issue Date: | 28-Nov-2019 |
Date of Acceptance: | 26-Nov-2019 |
URI: | http://hdl.handle.net/10044/1/75471 |
DOI: | 10.1016/j.neuropharm.2019.107868 |
ISSN: | 0028-3908 |
Publisher: | Elsevier |
Start Page: | 1 |
End Page: | 15 |
Journal / Book Title: | Neuropharmacology |
Volume: | 170 |
Copyright Statement: | © 2019 Published by Elsevier Ltd. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: | Disease modification Drug discovery Epilepsy Gene regulatory network Integrative genomics Network RNA-seq Regulome Single-cell Systems genetics Transcriptomics scRNA-seq snRNA-seq Drug discovery Epilepsy Gene regulatory network Integrative genomics Network RNA-seq Regulome Systems genetics Transcriptomics disease modification scRNA-seq single-cell snRNA-seq Neurology & Neurosurgery 1109 Neurosciences 1115 Pharmacology and Pharmaceutical Sciences 1701 Psychology |
Publication Status: | Published online |
Conference Place: | England |
Article Number: | ARTN 107868 |
Online Publication Date: | 2019-11-28 |
Appears in Collections: | Faculty of Medicine Department of Brain Sciences |