Project Details
Projekt
Antibody neutralization for treatment of autoimmune encephalitis
Subject Area
Molecular and Cellular Neurology and Neuropathology
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 415914819
Patients with N-Methyl-D-Aspartat receptor (NMDAR) encephalitis present with a rapid progression of neuropsychiatric manifestations that may lead to long-lasting coma within weeks. Immunosuppressive treatment has only a delayed efficacy. In the first funding period, we succeeded in developing fusion constructs consisting of the Fc part of immunoglobulin G (IgG) and parts of NMDARs, which neutralize the pathogenic effects of anti-NMDAR autoantibodies. The first aim of this project is to investigate the applicability of these constructs with a particular focus on crossing the blood-brain barrier (BBB). We will engineer bispecific Fc fusion proteins containing antibody parts to enable BBB crossing, screen these constructs in simplified models of the BBB, and test the best constructs in mice. The second aim of this project is to extend the developed concept to other forms of autoimmune encephalitis. We will focus on limbic encephalitis associated with autoantibodies against the leucine-rich glioma inactivated 1 (LGI1) protein, as LGI1 encephalitis is almost equally frequent as NMDAR encephalitis and peripheral antibody production is particularly common here. Further exploring the concept of antibody neutralization offers the chance to develop new treatment avenues in antibody-mediated CNS disease.
DFG Programme
Research Units
