Biomarkers for improved disease prognosis and therapy
Despite considerable progress in the research and treatment of MS, prognostic and predictive markers are still lacking which would help to identify optimal and individual choice of treatment as well as allow for comprehensive evaluation of therapy response and therapy risks. In the face of an increasing number of available treatment options, individual therapy decisions and better instruments for monitoring and prognosis are crucial.
Researchers in the consortium „Prognostic and treatment markers“ are working to define immunological and imaging characteristics as markers for prognosis, treatment success and treatment risks. For this, five subprojects use biosamples and MRI data from KKNMS network.
The project „ImmuneMS“ investgates the immune cell profile of patients with early MS and compares it to healthy controls as well as to patients with other neuroimmunological diseases. The researchers aim to determine whether there are MS-specific changes in the immune cell profile and whether these correlate with established parameters of disease activity (for example the presence of gadolinium-enriched lesions, T2-weighted lesions, the rate of attacks and EDSS progression). Potential markers will also be identified which will serve to predict clinical stability or disease progression. The researchers are furthermore interested in possible predictors of good therapy response and their correlation with established diagnostic and therapeutic markers. The changes in the immune cell profile will also be observed over a time course. Did they remain stable or was their development dependent on disease activity? Was it possible to identify changes in the immune cell profile which indicate failure of therapy later on? The scientists will also examine genetic factors which could influence the immune signature.
The project ImmuneMS will be performed at the University of Münster by Prof. Dr. Heinz Wiendl, PD Dr. Luisa Klotz and Dr. Catharina C. Groß.
Up to now we know very little about the network architecture of the brain of MS patients. However, the pattern could be a potentially promising marker for disease activity, prognosis and therapy response. The MRI signature project MSNetworks will study how the aspects of MS are reflected in the network architecture of the brain. The aim is to characterize network structures of white and grey matter and identify surrogates for disease course, prognosis and response to treatment of multiple sclerosis. For this project algorithms from MRI data generated in KKNMS cohorts as well as local cohorts of the University of Main will be derived and validated.
MSNetworks will be carried out by Prof. Dr. Frauke Zipp, Prof. Dr. Sergiu Groppa and Dr. Felix Lüssi at the Johannes Gutenberg University of Mainz.
The subproject BlginMS will study the role and relevance of B cells and specific antibodies as markers for MS phenotypes, prognosis and therapy response.
In the first two funding periods, the research team of Prof. Dr. Meinl (University of Munich) identified two soluble receptors, sBCMA and sTACl, which are increased by B cell receptors in the cerebrospinal fluid of MS patients. Now the team will focus on finding out whether these two new biomarkers can be used as prognostic factors and indicators of therapy response.
The researchers will also further study an observation they made in the past funding period: they found that auto-antibodies against MOG, which probably have a demyelinating effect, are not only present in some children with MS and patients with opticus neuritis and NMO spectrum disorders but also in a small percentage of adults with the relapsing form of MS. They would like to identify the clinical characteristics of patients with MOG antibodies and analyze their therapy responses from a clinical standpoint.
The project will be carried out at the University of Munich and headed by Prof. Dr. Edgar Meinl and Prof. Dr. Reinhard Hohlfeld.
Alemtuzumab is a monoclonal antibody which leads to fast and almost complete removal of T and B lymphocytes in the blood. After treatment, these cells are produced anew by precursor cells. During the new production, the immune system‘s balance shifts toward anti-inflammatory cells and factors so that the immune system is „reprogrammed“. In its approval studies, alemtuzumab showed a high effectivity in the treatment of relapsing MS. The effects of the treatment last for several years which, due to the considerable side effects, can be demanding for both patients and physicians. The immune mechanisms behind the effects and side effects of alemtuzumab are still for the most part unknown. The project ProgramMS has the goal of elucidating these mechanisms to identify strategies and signatures with which to predict the effectiveness and risks of alemtzumab therapy and in the long run improve the effects and the safety of the drug.
ProgramMS is a project cooperation between the University of Münster and the University of Heidelberg. It will be headed by Prof. Dr. Dr. Sven Meuth, Prof. Dr. Heinz Wiendl, Dr. Tobias Ruck and Prof. Dr. Brigitte Wildemann.
When changing treatment of natalizumab or fingolimod to another MS therapy, during the washout phase clinically and radiologically measurable disease activity may occur. The reasons behind this so-called rebound are not known; in particular, suitable biomarkers are still lacking which would make it possible to identify early on which patients may be at risk. The project ReboundMS will thus investigate T and B cell stability and immune reactivity shortly before the end of MS immune therapy as well as during the washout phase and shortly after begin of the new drug treatment.
The project will be headed by Prof. Dr. Brigitte Wildemann (University of Heidelberg), with support by PD Dr. Jürgen Haas (University of Heidelberg), Prof. Dr. Hayrettin Tumani (University of Ulm), Prof. Dr. Frauke Zipp (University of Mainz),Prof. Dr. Heinz Wiendl and Prof. Dr. Dr. Sven Meuth (both of the University of Münster). Multicentric recruitment of patients will be done in Heidelberg, Münster, Ulm and Mainz.
The consortium „Prognostic and Treatment Markers“ will be lead by Prof. Dr. Heinz Wiendl (University of Münster) together with Prof. Dr. Frauke Zipp (University of Mainz) and Prof. Dr. Reinhard Hohlfeld (University of Munich).