Pilot Cohort

Autoimmune neuropathies with autoantibodies against paranodal proteins

Autoimmune neuropathies are a heterogeneous disorder and pathogenic autoantibodies against paranodal proteins were recently described in a subset of patients. Some patients develop a chronic course of disease that is cause by autoantibodies of the subclass IgG4, others have a monophasic disease with mostly IgG3 autoantibodies. Our department was significantly involved in the description of this new subtype of autoimmune neuropathies, providing excellent preconditions to establish a database/network to support research on this rare condition. Such a database/network will provide the opportunity of clinical studies as well as biomaterial for experimental research. In continuation of our existing experimental focus, we would like to unravel the pathogenic mechanisms of autoantibodies in their target tissue (A). Another project that focuses on the identification of new autoantigens has just started (B). A new project field is supposed to elucidate mechanisms that induce a chronic course of disease in some patients. As our long-term goal, we aim to identify autoantibodies as a biomarker in as many patients as possible to allow a specific therapy (B) and to identify pathogenic mechanisms at the level of autoantibody binding as well as cause of autoimmunity as a prerequisite for the development of specific therapies in the future. Knowledge on the pathogenesis of IgG3-/IgG4-associated chronic and monophasic autoimmune disorders is supposed to be transferred to other IgG3-/IgG4-related disease and can be used in research groups and collaborations far beyond neuropathy research.

Motor adaptive capacity – multimodal quantification and clinical evaluation of a potential prognostic factor in neurodegenerative disease

Neurodegenerative disorders are characterized by loss of specific neuronal populations, along with increasing clinical impairment. The individual disease course may be described as the balance between disease-related pathology and intrinsic mechanisms of adaptation. New treatment strategies should target both sides of this interplay to be most effective. The term “adaptive capacity” refers to the capability of systems to successfully adjust to internal or external changes. Mainly coined in the field of cognitive neuroscience, the underlying concept may be transferable to motor adaptation. However, to date, there is no gold standard as to how the motor adaptive capacity may be quantified. Moreover, it remains undetermined to what extent this parameter contributes to the eventual course of neurological diseases. Therefore, this project aims (i) to quantify motor adaptive capacity and (ii) to put this measure to the test of whether it shows significant association with disease course. In a multimodal approach, behavioral measures, MR imaging, and questionnaires will be used to assess the adaptive capacity in healthy subjects (active/inactive). Subsequently, the optimized parameters will be tested in persons with Parkinson´s disease, ALS, and in a geriatric population on their association with the clinical course. Hand and gait function and clinical scores are recorded at enrollment and will be followed up one year after. An extension of our approach to other neurological conditions is intended. We expect our project to expedite our understanding of differences in individual resiliency towards disease-related challenges. This will eventually contribute to new, individually tailored therapeutic strategies aiming at an early and effective enhancement of the adaptive capacity.