Experimental models of multiple sclerosis and neuromyelitis optica
To further our understanding, and thus also the treatment, of neuroinflammatory diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum diseases (NMOSD), first characteristic changes in humans must be identified. It will then be possible to study these changes in certain parts of the immune and nervous systems which contribute to the pathological inflammatory process. Such analysis of the genetic or phenotypical changes requires pre-clinical test systems, i.e. models of the disease with which the situation in the human body can be reconstructed and investigated.
The most common models such as EAE, a disease resembling MS which is generated in an animal model, are primarily aimed at reconstructing and measuring the role of certain immune cells, the CD4+ T cells, in the disease process. Similarly developed models and measuring methods for other types of cells or other neuroinflammatory processes are presently not available. In the consortium „Modelling“, researchers aim to fill this gap by developing further and improved pre-clinical test systems.
Neuromyelitis optica (NMO) is a chronic inflammatory disorder of the central nervous system. Our knowledge of the disease to date indicates that T cells are involved in the development of NMO, yet their exact role is still not clear.
The subproject aims to observe and characterize CD4+ T cells in MS and NMO models of the rat. The decisive question here is how autoreactive T cells that are directed against the central nervous system modulate the reaction against the water channel aquaporin-4 (AQP4) which is involved in triggering the disease in humans.
The project will be carried out at the Institute of Neuroimmunology of the University Medical Center Göttingen by Prof. Dr. Alexander Flügel and Dr. Dmitri Lodygin.
Neuromyelitis optica (NMO) is the only autoimmune disease of the central nervous system whose target antigen is known – the immune response is directed against the water channel aquaporin-4 (AQP4). While it is hypothesized that this immune response is involved in the development of NMO, only little is known about the role of T cells in the activation of the AQP4 antibody.
In this project, tools and models will be established with which the formation of aquaporin-4-specific T cells in the peripheral immune system and their interaction with B cells during the antigen-specific sensibilization will be investigated.
The project is headed by Prof. Dr. Thomas Korn (TU Munich).
Researchers of the subproject „CD8 model“ will examine the hypothesis that CD8+ T cells play a significant role in the development of MS and related disorders. They hypothesize that this can be simulated in mouse models using a genetically altered T cell receptor (TCR). The goal of the project is a comprehensive characterization of the autoreactive CNS-specific CD8+ T cell response in mice and the generation of new CD8+ TCR transgenic mouse models of MS. These will contribute to a better understanding of the phenotypes and functions of CSF- and CNS-infiltrating cells.
The project will be carried out by Prof. Dr. Manuel A. Friese of the University Medical Center Hamburg-Eppendorf.
Several highly specialized types of bone marrow cells are present in the central nervous system (CNS). While many of these myeloic cells are very similar to each other, they greatly differ in their function in autoimmune inflammation of the CNS and their relevance is still unknown. This project aims to utilize new methods of high throughput sequencing to newly characterize myeloic cells during EAE in the mouse model and in MS in humans and thus clarify their role in the development of neuroinflammation.
The project will be headed by Prof. Dr. Marco Prinz at the Institute of Neuropathology, University Medical Center Freiburg.
In this project, improved preclinical assessment strategies for the most important parameters that determine the phenotype of a neuroinflammatory disorder will be developed: the severity of the disease symptoms, the localization of disease activity and the pattern of neuroglial damage. For this the group will utilize differentiated behavioral physiological test methods to more effectively determine the extent of neurological deficits. Furthermore, new approaches will be developed to measure the pathology of grey matter and cellular and molecular microscopy techniques will be used to monitor damage to nerve and glia cells in intact tissues. These approaches will help investigate the role of new disease-modulating genes and signal pathways which will be identified in the MS cohort study.
The project will be carried out by Prof. Dr. Martin Kerschensteiner (University of Munich) and PD Dr. Gurumoorthy Krishnamoorthy (Max Planck Institute of Biochemistry).
The consortium modelling will be headed by Prof. Dr. Martin Kerschensteiner (University of Munich ) and Prof. Dr. Alexander Flügel (University of Göttingen).