Neuroinflammation in Schizophrenia: Targeting IL-1ß Signaling with NLRP3 Inhibitors

This proposal aims to validate the NLRP3 inflammasome as a novel therapeutic target in a biologically defined subgroup of schizophrenia patients with neuroinflammation, marked by elevated IL-1β. Schizophrenia affects 1 in 100 people worldwide, yet current treatments are only partially effective, highlighting the urgent need for new therapeutic strategies. Emerging evidence implicates NLRP3–IL-1β signalling in immune dysregulation within a subset of patients. This study will use patient-derived induced pluripotent stem cell (iPSC) models to recreate brain-like environments and validate the NLRP3 inflammasome as a potential therapeutic target in schizophrenia. Specifically, we will (1) investigate aberrant NLRP3 activation in patient-derived iPSC models and (2) assess whether brain-penetrant NLRP3 inhibitors can reverse the deleterious effects of neuroinflammation. Shaped by input from people with lived experience, the project prioritises biologically informed, early-stage interventions. Overall, this work will generate a key dataset that could accelerate the translational pipeline for immune-targeted treatments in a subset of patients who are not well served by current therapies.