KFO 5023: BECAUSE-Y Berlin Center for Diagnosing, Understanding and Treating Antibody(Y)-mediated Neurological Diseases

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The discovery of a number of distinct antibody-mediated diseases of the nervous system has profoundly changed the landscape in Neurology. First work demonstrated the pathogenicity of several antibodies targeting neuronal surfaces and, thereby, helped to re-classify diagnoses and allowed specific treatment of patients with encephalitis, dementia, epilepsy, psychosis as well as neuromuscular dysfunction. The rapidly increasing scientific advancements suggest that many more clinical symptoms may relate to humoral autoimmunity. Moreover, autoantibodies may also play an additive pathogenic, disease-modifying or even causal role in conditions not previously thought to be immune-mediated. Consequently, there is a strong medical need to determine the frequency, target epitopes and function of autoantibodies in central nervous system diseases, to develop novel diagnostic assays and brain imaging, to understand factors contributing to the initiation and pathogenesis of antibody-mediated neurological diseases, and to develop highly antibody-selective immunotherapies. The proposed DFG Clinical Research Unit (CRU) BecauseY at Charité and DZNE Berlin is unique by addressing this need for “personalized” medicine in a coordinated and integrated fashion. The central structural feature is a tertiary Core Unit for Research and Treatment in Berlin as a comprehensive center for diagnosing and treating antibody-mediated neurological diseases. It will be underpinned by a highly connected research network comprising eight subprojects with shared infrastructure, personnel, and scientific concepts, focusing on understanding of disease mechanisms (P1-P4), diagnostics (projects P4-P6), and novel selective immunotherapy concepts (P7-P8), each represented by a team of clinician and basic scientists. The principal investigators have been conducting internationally recognized work in the field of antibody-mediated and autoimmune diseases, allowing the projects to span a broad methodological spectrum. Along the patients’ paths through the CRU, there will be continuous transfer of knowledge and material between the subprojects, e.g. acquisition and banking of biosamples, clinical data, escalation of immunotherapies, translational application of newest diagnostic procedures, nosological understanding of disease mechanisms, assessment of antibody function in animal models, and first-in-human investigator-initiated trials of immunotherapy. The clinical research-oriented structure of BecauseY will directly benefit patients and strongly enhance the scientific profile of the Department of Neurology, the Charité and the DZNE Berlin. It can provide an attractive environment for additional top-level clinical research at the border zone between autoimmunity and neuroscience. Finally, it holds potential to establish a unique university-based comprehensive center for integrated care of patients with antibody-mediated diseases.