In autoimmune encephalitis, a rare but serious and sometimes life-threatening inflammation of the central nervous system, the body’s defenses turn against the central nervous system. This disease was first described in 2007. Anti-NMDA receptor encephalitis is the most common. In this autoimmune disease, a protein is disrupted that plays an important role in signal transmission in the brain: the NMDA-type glutamate receptor, or NMDA receptor for short. Researchers from Braunschweig, Jena, Leipzig and Berlin have developed a new potential therapeutic agent against this disease.
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In anti-NMDA receptor encephalitis, antibodies disrupt signal transmission in the brain:
The receptor to which the neurotransmitters glutamate and glycine bind is taken up by the antibody binding into the cell. This leads to reduced signal transmission to neurons in the central nervous system. Those affected develop psychoses such as hallucinations, epileptic seizures and clouding of consciousness up to coma. Patients describe the symptoms of the disease as a ‘fire in the brain’ that they cannot influence. The interdisciplinary and cross-location DFG research group “SYNABS” is dedicated to researching this disease.
New therapeutic approaches
“It is our goal to better understand the disease mechanisms and to develop new and target-specific therapeutic approaches using modern biotechnology ,” says the spokesman for the group, Professor Christian Geis from the University Hospital Jena. With their translational research approach, the group has now discovered a potential therapeutic agent. The molecule consists of a part of the NMDA receptor and a constant part of a human antibody. The disease-causing antibodies then bind to this fusion construct and no longer to the NMDA receptors.
We were able to demonstrate the effectiveness of this molecule in controlled behavioral studies with mice.
In animals with autoimmune encephalitis that had received the drug candidate, memory formation was almost the same as in healthy animals. In diseased animals without therapy, it was clearly impaired ,” explains Eleonora Loi, a doctoral student at Jena University Hospital in the SYNABS consortium. The Jena project team also investigated the physiological properties of the molecule in tissue.
In this project, the TU Braunschweig developed
The active substance molecule and analyzed it biochemically. The partners at the University Hospital Jena and Medicine at the University of Leipzig initiated the DFG research group and carried out the analysis on nerve cells and in vivo studies. The partners at the Charité and Freie Universität in Berlin have identified the autoimmune antibodies of patients.