Early Insights Into ALS Mutation and Therapeutic Targeting

Scientists at Case Western Reserve University report that the familial ALS-linked VAPB P56S mutation activates the integrated stress response (ISR) via mitochondrial dysfunction in motor neurons. Pharmacological ISR inhibition using ISRIB rescues ALS phenotypes in patient-derived motor neurons. Published in EMBO Molecular Medicine, this study mechanistically connects a known ALS mutation to ISR activation, highlighting potential mutation-specific therapeutic approaches and patient stratification strategies in ALS clinical trials.