DNL343

DNL343 is a brain-penetrating activator of eukaryotic initiation factor 2B (eIF2B) that inhibits the abnormal integrated stress response (ISR) . DNL343 inhibits ISR activity in the central nervous system (CNS) and reverses neurodegeneration and neuroinflammation. DNL343 also prevents motor dysfunction and premature death in eIF2B loss-of-function (LOF) mutant mice. DNL343 has inhibitory potential in studies of vanishing white matter disease (VWMD) driven by eIF2B LOF and chronic ISR activation.