Against the "fire in the brain"

In autoimmune encephalitis, a rare but serious and sometimes life-threatening inflammation of the central nervous system, the body's own defences are directed against the central nervous system. This disease was first described in 2007, with anti-NMDA receptor encephalitis being the most common. In this autoimmune disease, a protein is disrupted that plays an important role in the transmission of signals 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 for this disease.

In anti-NMDA receptor encephalitis, antibodies interfere with the transmission of signals in the brain: the receptor to which the neurotransmitters glutamate and glycine bind is absorbed into the cell through the antibody binding. This results in reduced signalling to neurons in the central nervous system. Those affected experience psychoses such as hallucinations, epileptic seizures and disturbances 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-locational DFG Research Unit „SYNABS“ is dedicated to researching this disease.

„Our aim is to gain a better understanding of the disease mechanisms and to develop new and target-specific therapeutic approaches using modern biotechnology,

„ says the group's spokesperson, Prof Dr Christian Geis from Jena University Hospital. 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 pathogenic antibodies then bind to this fusion construct and no longer to the NMDA receptors.

„To investigate whether the newly developed molecule can neutralise the antibodies, we used biochemical and microscopic methods on cultured nerve cells from mice and humans," says Toni Kirmann, doctoral student in the SYNABS consortium at the Faculty of Medicine at Leipzig University. We will try to transfer this therapeutic concept to other forms of autoimmune encephalitis. In the long term, we hope that basic neuroscientific research will help to improve therapeutic options in neurology and psychiatry," adds Prof Dr Stefan Hallermann from the Carl Ludwig Institute of Physiology, Faculty of Medicine at Leipzig University.

The TU Braunschweig developed and biochemically analysed the active ingredient molecule in this project. The partners at Jena University Hospital and Leipzig University Medical Centre initiated the DFG research group and carried out the analysis on nerve cells and in vivo studies. The partners at Charité and Freie Universität in Berlin have identified the autoimmune bodies of patients.

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Original publication in "Brain": 
NMDA-receptor-Fc-fusion constructs neutralise anti-NMDA receptor antibodies
DOI: https://doi.org/10.1093/brain/awac497

Press release of the University Hospital Leipzig from 03/03/2023