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

许多截然不同的抗体介导的神经系统疾病的发现，深刻地改变了神经学的格局。第一项工作证明了几种针对神经元表面的抗体的致病性，从而帮助重新分类诊断，并允许对脑炎、痴呆症、癫痫、精神病以及神经肌肉功能障碍的患者进行特定治疗。快速增长的科学进步表明，更多的临床症状可能与体液自身免疫有关。此外，自身抗体还可能在以前认为不是由免疫介导的疾病中发挥相加的致病、疾病修改甚至因果作用。因此，迫切需要确定自身抗体在中枢神经系统疾病中的频率、靶位和功能，开发新的诊断方法和脑成像，了解抗体介导的神经系统疾病的启动和发病机制，以及开发高度抗体选择性的免疫疗法。拟议中的DFG临床研究单位(CRU)在Charité和DZNE柏林分部是独一无二的，它以协调和集成的方式满足了对“个性化”药物的需求。中心结构特征是位于柏林的第三研究和治疗核心单位，作为诊断和治疗抗体介导的神经疾病的综合中心。它将得到一个高度连接的研究网络的支持，该网络由八个子项目组成，共享基础设施、人员和科学概念，重点是了解疾病机制(P1-P4)、诊断(P4-P6项目)和新的选择性免疫治疗概念(P7-P8)，每个子项目都由一个临床医生和基础科学家团队代表。主要研究人员一直在抗体介导的疾病和自身免疫性疾病领域开展国际公认的工作，使这些项目能够跨越广泛的方法学范围。沿着患者通过CRU的道路，将在子项目之间不断传递知识和材料，例如生物样本的获取和存储、临床数据、免疫疗法的升级、最新诊断程序的翻译应用、疾病机制的病因学理解、动物模型中抗体功能的评估，以及人类研究人员发起的首个免疫疗法试验。BecauseY以临床研究为导向的结构将直接造福于患者，并有力地提升神经内科、Charité和DZNE柏林的科学形象。它可以为在自身免疫和神经科学之间的边界地带进行额外的顶级临床研究提供一个有吸引力的环境。最后，它有可能建立一个独特的以大学为基础的综合中心，为抗体介导的疾病患者提供综合护理。

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.