Advanced Clinician Scientist-Programm 2026

Thema: "Creating an active immunization model of CASPR2 encephalitis"

Zusammenfassung:
Autoimmune encephalitis is a group of inflammatory brain diseases characterized by neuropsychiatric symptoms, seizures, and cognitive deficits. CASPR2 encephalitis, one of the most prevalent subtypes of AE, manifests as limbic encephalitis. Animal models of passive transfer using IgG from patients diagnosed with CASPR2 encephalitis indicate the direct pathogenicity of CASPR2 autoantibodies. However, these passive-transfer models are very limited because the role of immune cells in the pathophysiology of the disease and novel therapeutic approaches cannot be tested. Additionally, the passive transfer model does not produce spontaneous seizures, which limits its direct application to human disease. This study aims to develop and characterize a mouse model of CASPR2 encephalitis using active immunization with functionally relevant protein domains and diverse adjuvants to enhance the immune response. Using behavioral, electrophysiological, and molecular biological methodologies, we will elucidate the pathomechanisms underlying the disease and its long-term effects on cognitive function. Developing an animal model of CASPR2 encephalitis will improve our understanding of the immune system's role in the disease and the pathophysiology of the antibody. This research could lead to more effective therapeutic interventions.