Multiple sclerosis
Multiple sclerosis is a presumably autoimmune-mediated disease of the central nervous system. An inflammatory reaction causes damage to the myelin sheath and nerve structures. We are working on a number of scientific issues:
Clinical studies in the field of MS therapy range from phase II to phase IV studies as well as smaller, academically initiated, so-called Investigator Initiated Trials (IIT).
Translationally, we deal with biomarkers in the cerebrospinal fluid. We use both traditional diagnostic methods and modern methods such as mass spectroscopy.
In the area of basic research, the focus of our work is on the mechanisms of how regeneration with remyelination occurs and how this can be improved. We use both cell cultures and animal models.
Neuroinfectiology
Various pathogens can infect the nervous system. Scientifically, we are mainly concerned with viral pathogens that cause inflammation of the meninges (meningitis) or the brain (encephalitis), for example. In clinical translational research, we investigate metabolites in cerebrospinal fluid as potential biomarkers for faster diagnosis or as prognostic markers. In basic research, we are experimentally investigating the role of glial cells during viral infections of the brain. This work is carried out in close cooperation with the TWINCORE Institute for Translational Infection Research, the Center for Individualized Infection Research (CiiM) and the RESIST Cluster of Excellence.
Autoimmune and infectious encephalitis
PD Dr. med. Kurt-Wolfram Sühs
The working group focuses on clinical and basic research projects on neuroimmunological mechanisms in inflammatory diseases of the nervous system, in particular autoimmune and infectious encephalitides.
Overall, the understanding of neuroimmunological diseases and the associated treatment options have improved considerably as a result of global research efforts, although there are still significant individual differences in symptom severity and prognosis. Autoimmune and infectious encephalitides in particular are often serious, acute-subacute manifestations of diseases of the central nervous system with sometimes significantly different clinical residuals. They are therefore often initially treated in intensive care, followed by normal inpatient and finally outpatient treatment, resulting in different clinical aspects and questions.
The pathophysiological mechanisms underlying these diseases, which factors influence the diseases and disease severity and, in particular, whether these influences can be utilized translationally for diagnostics, individual prognosis assessment and therapy are the central questions of the working group.
In our working group, for example, the influence of ion channels on experimental models and in cell cultures is investigated in basic scientific experimental work. In addition, the clinical characterization and investigation of biomaterial, in particular changes in the cerebrospinal fluid, is carried out using modern techniques such as mass spectrometry. In addition to interdisciplinary collaborations (neuroradiology, psychiatry, immunology, etc.), due to the rarity of certain diseases such as antibody-mediated encephalitis, cooperation takes place in large network alliances (e.g. GENERATE). Experimentally, there is close cooperation with TWINCORE, particularly with regard to infectious diseases.
1 Immunofluorescence (hippocampus) with antibodies against NR1 (green) and the astrocyte marker GFAP (red) . 2 NR1 expression (red) in the retina with counterstaining of the neuronal cell bodies (NeuN, green).
A Hierarchical cluster analysis based on the discriminatory power of metabolic biomarker candidates in CSF. B Jackknife cross-validation C-F box/scatter plot showing the concentration differences d of selected biomarker candidates from Figure B.
III GENERATE Centers- GErman NEtwork for REsearch on AuToimmune Encephalitis
Selected publications:
Baumgärtel C, Skripuletz T, Kronenberg J, Stangel M, Schwenkenbecher P, SinkeC, Müller- Vahl KR, Sühs KW. Immunity in Gilles de la Tourette Syndrome: Results from a Cerebrospinal Fluid Study. Front Neurol. 2019 Jul 4; 10:732.
Sühs KW, Novoselova N, Kuhn M, Seegers L, Kaever V, Muller-Vahl K, et al. Kynurenine is a cerebrospinal fluid biomarker for bacterial and viral CNS infections. J Infect Dis 2019 Jun 5; 220(1):127-138.
Kuhn M, Sühs KW, Akmatov MK, Klawonn F, Wang J, Skripuletz T, et al. Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation. J Neuroinflammation 2018 Jan 17;15(1):20.
Sühs KW, Fairless R, Williams SK, Heine K, Cavalie A, Diem R. N-methyl-D-aspartate receptor blockade is neuroprotective in experimental autoimmune optic neuritis. J Neuropathol Exp Neurol 2014 Jun;73(6):507-18.
Sühs KW, Hein K, Sattler MB, Gorlitz A, Ciupka C, Scholz K, et al. A randomized, double- blind, phase 2 study of erythropoietin in optic neuritis. Ann Neurol 2012 Aug;72(2):199-210.
Further links and networks:
Centre for Rare Diseases www.mh-hannover.de/37762.html
GENERATE generate-net.de
TWINCORE www.twincore.de/institute/experimentelle-infektionsforschung/forschungsfokus/
Inflammatory polyneuropathies and Neuro-Sjögren's disease
Prof. Dr. med. Thomas Skripuletz
The working group deals with polyneuropathies caused by a misdirected immune system. This is a very heterogeneous group of diseases that includes different clinical pictures. Well-known representatives of inflammatory polyneuropathies are chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Another disease that can lead to severe polyneuropathies is Sjögren's syndrome (Neuro-Sjögren's), which is a particular focus of the working group.
In inflammatory polyneuropathies, patients can experience severe disabilities with paralysis of the arms and legs caused by nerve damage, which can result in an inability to walk. Important goals of the working group are therefore to understand the causes of such diseases and to find new markers in order to improve diagnostics so that affected patients can be treated more quickly and reliably in future. Further goals are to better understand the treatment options used in order to apply the ideal therapy for each patient.
Another focus of the working group is on basic research with examinations of blood and cerebrospinal fluid. Using various techniques, the aim of the working group is to find new markers for neuroimmunological diseases such as multiple sclerosis in order to be able to diagnose these diseases more quickly and reliably in the future.
Focus on NMOSD
Prof. Dr. med. Corinna Trebst
The working group deals with neuromyelitis optica spectrum disorders (NMOSD). These are rare, relapsing diseases of the central nervous system. As a large NEMOS center (link : www.nemos-net.de), we are networked throughout Germany and internationally and take part in the NationNMO cohort study of the KKNMS and drug trials. Our particular research interest is the evaluation and optimization of (also experimental) forms of therapy. Together with 17 other NEMOS centers throughout Germany, we also play a leading role in investigating the effects of this disease on quality of life and socio-economic factors. Another focus is on the detailed characterization of MOG-IgG associated diseases / NMOSD.
Responsible contact persons:
Prof. Dr. Corinna Trebst (link to personal profile)
Dr. Martin Hümmert
Selection of publications:
https://www.ncbi.nlm.nih.gov/pubmed/?term=trebst+c+nmosd
Link to further websites:
Neuromyelitis optica study group
Centre for Rare Diseases of the MHH - Center for Rare Autoimmune Encephalomyelitis