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.
References:
[1]. Yulyaningsih E, et al. DNL343 is an investigational CNS penetrant eIF2B activator that prevents and reverses the effects of neurodegeneration caused by the Integrated Stress Response[J]. bioRxiv, 2023: 2023.8.21.554203