The autoimmune brain inflammation
A good ten years ago, autoimmune brain inflammation was first described in the medical literature. In the meantime, neurologists are familiar with a whole family of these rare diseases, which mostly affect young adults. Triggered by certain tumors, infections or mostly still without a recognizable cause, antibodies against neurotransmitter receptors in the central nervous system are produced, which disrupt the signal transmission at the contact points of the nerve cells, the synapses. The consequences can be confusion, psychosis, epileptic seizures or disturbances of consciousness.
"We want to develop a detailed understanding of the mechanisms of the different forms of autoimmune encephalitis", Prof. Dr. Christian Geis describes the goal of the SYNABS research group. The neuroimmunologist from the University Hospital Jena is spokesman of the group, which will be funded by the DFG with 3.9 million Euros over the next three years. The group consisting of neurologists, neuroscientists, physiologists, neuroimmunologists and biotechnologists from research institutions in Germany and Austria will investigate disease mechanisms for different receptors on the molecular level, in animal models and using human tissues and recombinant antibodies.
Combination of clinical-experimental and basic research
The working group around Prof. Dr. Josep Dalmau in Barcelona is also associated. The pioneer in the field of antibody-based encephalitis is funded as a Mercator Fellow. "In each of our eight subprojects, specialists from clinical-experimental research as well as basic scientists with special methodological expertise work together", describes Prof. Dr. Stefan Hallermann, neurophysiologist at the University of Leipzig and deputy spokesman of the group, the interdisciplinary research approach. In each case, highly specialized experimental methods such as electrophysiology and calcium imaging, biotechnology and electron and super-resolution microscopy are used.
Identifying the composition of each synapse
In one project, the scientists from Jena and partners in Würzburg will investigate the direct effect of antibodies obtained from patient material against the NMDA receptor by measuring the signal flow at the individual receptor. At the same time, potentially therapeutically effective molecules will be identified. Together with the Charité in Berlin, they will also study the immune response at the GABA-B receptor, which belongs to a different receptor family. Christian Geis: "We want to clarify the resulting changes in the function and composition of the individual synapses, right down to the cause of epileptic seizures and memory disorders". A collaboration, also with Berlin partners, is investigating whether and how autoantibodies in maternal blood affect the prenatal brain development of a baby. Here, the neurologist PD Dr. Knut Kirmse from Jena contributes his experience in imaging network activity in the brain.
For patients with autoimmune encephalitis, there is currently only a general therapy available that non-specifically suppresses the immune reaction. "With our translational research program we want to better understand these diseases and develop new and target-specific therapeutic approaches using modern biotechnology", says Prof. Geis.
SYNABS partner:
-Friedrich Schiller University Jena, University Hospital Jena, Section of Translational Neuroimmunology, Clinic for Neurology
-University of Leipzig, Carl-Ludwig-Institute of Physiology
-Humboldt University Berlin, Charité, Department of Neurology,
-Clinic for Pediatrics with focus on Neurology, German Center for Neurodegenerative Diseases (DZNE) Berlin
-University of Würzburg, Physiological Institute, Biocenter; University Hospital Würzburg, Neurological Clinic, Institute for Clinical Neurobiology
-German Cancer Research Center (DKFZ) Heidelberg
-Technical University of Braunschweig, Department of Biotechnology
-Institutes of Science and Technology Austria (IST Austria), Vienna/Klosterneuburg
-MedUni Vienna, Clinical Institute of Neurology (Obersteiner Institut)
associated:
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic IDIBAPS Barcelona, Department of Neurology
Contact:
Prof. Dr. Christian Geis Sektion Translationale Neuroimmunologie, Klinik für Neurologie, Universitätsklinikum Jena Am Klinikum 1 07747 Jena Zum Lageplan +49 3641 9-323413
Uta von der Gönna