From cells and synapses to connectivity and cure in paediatric autoimmune encephalitis

Year of award: 2024

Grantholders

  • Dr Sukhvir Wright

    Aston University, United Kingdom

Project summary

Worldwide, one person every minute is diagnosed with encephalitis. An autoimmune cause is now as common as infectious (~27%). Autoimmune encephalitis (AE) patient outcomes remain static despite increasing recognition and earlier immunotherapy. Children are disproportionality poorly affected. My key goal in this CDA is to address the gap in our understanding why some acute AE symptoms resolve (e.g., seizures) but others become chronic (e.g., neuropsychiatric and sleep disorders), even when successfully treated at presentation. I have mapped acute AE symptoms in pre-clinical rodent models discovering convergence in pathophysiological autoantibody action at synaptic and circuit levels. My preliminary clinical Magnetoencephalography (MEG) studies in long-term survivors of paediatric AE show distinct brain network changes that correlate with cognitive measures. My hypothesis: Paediatric AE causes distinct acute cellular and synaptic changes, disrupting neuro-immune crosstalk, resulting in persistent brain structural and network changes which underlie the chronic symptoms. In pre-clinical AE models, I will characterise the mechanisms underlying these chronic AE neurological symptoms (e.g., sleep and neuropsychiatric disorders) at cellular, synaptic, and network levels. In paediatric AE patients I will examine longitudinal brain network changes. Combining these cross-species data will identify common pathophysiological targets for therapeutic intervention to reduce morbidity and improve long-term outcomes.