Putting out the fire in the brain DFG Research Unit Develops a Potential Treatment for Autoimmune Encephalitis

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 identified in 2007, and the most common type is Anti-NMDA receptor encephalitis. In this autoimmune disease, a protein that plays an important role in signal transmission in the brain is disrupted: the NMDA-type glutamate receptor, or NMDA receptor for short. Researchers from Braunschweig, Jena, Leipzig and Berlin have developed a new potential treatment for this disease.

In anti-NMDA receptor encephalitis, antibodies interfere with signal transmission in the brain. The receptors which the neurotransmitters glutamate and glycine bind to are internalised by the cells through antibody binding. This causes reduced signal transmission to neurons in the central nervous system. Those affected experience a wide variety of symptoms from epileptic seizures and psychoses such as hallucinations to loss of consciousness and coma. Patients describe the disease symptoms to be like a “fire in the brain” that they can’t control. The interdisciplinary DFG research unit SYNABS, consisting of researchers from several locations, is dedicated to the study of this disease.

“It is our goal to better understand the disease mechanisms and to develop new and target-specific therapeutic approaches using modern biotechnology,” said the group’s spokesperson, Professor Christian Geis from Jena University Hospital. With their translational research approach, the group has been able to discover a potential therapeutic agent. The molecule consists of a part of an NMDA receptor and a fragment of a human antibody. The pathogenic antibodies then bind to this fusion construct rather than to the NMDA receptors.

“We were able to analyze the functionality and effectivity of the molecule in several in vitro assays and in an in vivo model. With the current therapies, 25% of the patients have long hospitalization on the intensive care units, partly with coma for several month” says Stepah Steinke, PhD student at TU Braunschweig in the SYNABS consortium.

“Now, we have a lead molecule for the therapeutic development of this disease” says Prof. Michael Hust from the Institut für Biochemie, Biotechnologie und Bioinformatik at TU Braunschweig and member of the consortium. “We are working on the next steps, to transfer this therapeutic approach to other forms of autoimmune encephaltiis.”

In this project, TU Braunschweig developed the fusion construct and analysed it biochemically. The partners at Jena University Hospital and the Faculty of Medicine at Leipzig University initiated the DFG research unit and have analysed neurons and conducted in vivo studies. The partners at Charité and Freie Universität in Berlin have identified the affected autoimmune antibodies in patients.