Understanding the pathogenesis in CASPR2-antibody autoimmune synaptic encephalitis


Project Summary

Autoimmune synaptic encephalitis is a group of diseases with severe neurological symptoms, associated with autoantibodies that interfere with brain function. Contactinassociated protein 2 (CASPR2) is one of the synaptic antigens. We found that Caspr2 regulates glutamate receptors of the AMPA type (AMPAR), and hypothesize that the patients antibodies disrupt the function of Caspr2 in regulating AMPAR synaptic function, resulting in cognitive and behaviour disturbances. We will investigate the synaptic effects induced by patients' CASPR2 autoantibodies and develop and characterize a mouse model for the disease through passive infusion of patients CSF or purified antibodies into the mouse brain. We expect to contribute for a better understanding of how patients' CASPR2 antibodies exert their pathogenic effect and create a model that can recapitulate the disease symptoms, useful for testing further pathogenic mechanisms as well as experimental therapies.

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