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

许多不同的抗体介导的神经系统疾病的发现已经深刻地改变了神经病学的景观。第一项工作证明了几种针对神经元表面的抗体的致病性，从而有助于重新分类诊断，并允许对脑炎、痴呆、癫痫、精神病以及神经肌肉功能障碍患者进行特异性治疗。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，自身抗体也可能在以前不被认为是免疫介导的情况下发挥附加致病性、疾病修饰性甚至因果作用。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、靶表位和功能，开发新的诊断方法和脑成像，了解导致抗体介导的神经系统疾病的发生和发病机制的因素，并开发高度抗体选择性的免疫疗法。提议的DFG临床研究单位（CRU）因为在慈善和DZNE柏林是独一无二的，以协调和综合的方式解决“个性化”医疗的需求。中心结构特征是柏林研究和治疗的三级核心单位，作为诊断和治疗抗体介导的神经系统疾病的综合中心。它将以一个高度连接的研究网络为基础，该研究网络由八个子项目组成，具有共享的基础设施、人员和科学概念，重点是了解疾病机制（P1-P4）、诊断（项目P4-P6）和新的选择性免疫治疗概念（项目P7-P8），每个子项目都由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和自身免疫性疾病领域开展国际公认的工作，使项目跨越广泛的方法范围。在患者通过CRU的过程中，子项目之间将持续进行知识和材料的转移，例如生物样本的获取和储存、临床数据、免疫疗法的升级、最新诊断程序的转化应用、疾病机制的分类学理解、动物模型中抗体功能的评估以及首次在人体中进行的免疫疗法试验。临床研究型结构将直接惠及患者，并有力地提升神经内科、慈善基金会和柏林DZNE的科学形象。它可以为自身免疫和神经科学之间的边界地带的额外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基于大学的综合中心，对抗体介导的疾病患者进行综合护理。

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.