We previously showed that preventive treatment of homozygous R191H eIF2B-ε mice (hereafter referred to as R191HHOM) with an orally bioavailable small molecule eIF2B activator, 2BAct, prevents the development of VWM pathophysiology, fully suppresses the ISR, and normalizes the brain transcriptome and proteome (13), revealing its potential in modifying VWM etiology. This evidence concerns the gene EIF2B5 and leukoencephalopathy with vanishing white matter.