A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target.

Related Articles

A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target.

Nat Commun. 2018 09 03;9(1):3561

Authors: Srivastava PK, van Eyll J, Godard P, Mazzuferi M, Delahaye-Duriez A, Steenwinckel JV, Gressens P, Danis B, Vandenplas C, Foerch P, Leclercq K, Mairet-Coello G, Cardenas A, Vanclef F, Laaniste L, Niespodziany I, Keaney J, Gasser J, Gillet G, Shkura K, Chong SA, Behmoaras J, Kadiu I, Petretto E, Kaminski RM, Johnson MR

Abstract
The identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning ("Causal Reasoning Analytical Framework for Target discovery"-CRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy.

PMID: 30177815 [PubMed - indexed for MEDLINE]

from A via a.sfakia on Inoreader http://bit.ly/2MwLgXn