Biomarkers for axonal damage and neurodegeneration in MS

Multiple sclerosis (MS), the most common neurological disease among young adults, is a chronic disease of the central nervous system (CNS). It is a very heterogeneous disease with a wide spectrum of interindividual differences in regard to disease course and clinical manifestations but also concerning biochemical and pathological findings, magnetic resonance imaging features and response to immunomodulatory and immunosuppressive therapy. Consequently, tools, which could help to separate distinct patient subgroups regarding prognosis or response to therapy, are strongly needed. Research so far has also concentrated mainly on biomarkers of inflammatory and immunopathophysiological processes. However, recent data indicate, that axonal degeneration is a prominent pathological finding already at early stages of the disease both in MS and in experimental autoimmunencephalomyelitis (EAE), the animal model of MS. Nowadays, neurodegeneration is regarded as the major cause of irreversible neurological disability in MS patients. The exact mechanisms leading to neurodegneration in MS are largely unknown and it is disputed whether this may be a primary event or a phenomenon secondary to inflammation. Irrespective of the etiology it can be speculated that neurodegeneration by itself may lead to changes in body fluids, like CSF and blood, which could be potentially used as biomarkers for such processes. For many years the Clinical Department of Neurology at the Medical University of Graz has specialized in Multiple Sclerosis care and research with emphasis especially on neuroimaging, genetics and neurohistopathology. More recently we have implemented a biobank for CSF, serum, plasma and genetic material, which should ultimately serve to combine respective results with clinical and morphological data. The VUMC stands out due to the interdisciplinary Neurounit for Biomarkers for Inflammation and Neurodegeneration (NUBIN) in MS and Alzheimers Disease (AD) and the long experience with biomarker research in MS and other neurological diseases also by applying advanced laboratory techniques, including high- throughput MALDI TOF/TOF mass spectrometer (4800 ABI) and a nano-liquid chromatography system on-line coupled to LTQ-FT mass spectrometer. Therefore, a fellowship at the above mentioned institution would be of great benefit to further deepening the knowledge of biomarker research in MS with a focus on markers for axonal damage and neurodegeneration and to strengthen the respective research field at the Medical University of Graz. In the next step of this project, the acquired know-how will be immediately applied to CSF/serum samples from the VUMC and the biobank at the Medical University of Graz, which will ultimately serve to combine respective results with clinical and morphological data.