Drug Screening Identifies Sigma-1-Receptor as a Target for the Therapy of VWM Leukodystrophy.

ABSTRACT: Vanishing white matter (VWM) disease is an autosomal genetic leukodystrophy caused by mutations in subunits of eukaryotic translation initiation factor 2B (eIF2B). The clinical symptoms exhibit progressive loss of white matter in both hemispheres of the brain, accompanied by motor functions deterioration, neurological deficits, and early death. To date there is no treatment for VWM disease. The aim of this work was to expedite rational development of a therapeutic opportunity. Our approach was to design a computer-aided strategy for an efficient and reliable screening of drug-like molecules; and to use primary cultures of fibroblasts isolated from the Eif2b5^R132H/R132H VWM mouse model for screening. The abnormal mitochondria content phenotype of the mutant cells was chosen as a

SUBMITTER: Atzmon A 

PROVIDER: S-EPMC6153319 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature