T-cell-based Approaches for Controlling Autoimmune Disease with Epilepsy

• Applicants: Privatdozent Dr. Nico Melzer; Dr. Michael Strüber
• Subject Area: Clinical Immunology and Allergology ; Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 583034287

Autoimmune limbic encephalitis and Rasmussen's encephalitis are considered rare to ultra-rare forms ofautoimmune brain inflammation in children and adults presenting with seizures as well as behavioral (cognitive/motor) decline. Current evidence suggests that both diseases often develop into irreversible circumscribed brain atrophy and scarring with devastating treatment-refractory focal epilepsy. This process is mainly driven by neuron- and potentially also astrocyte-directed T cell responses. Currently, there is no approved tailored treatment option for T cell responses prevailing in both disease and no approved immunotherapy at all. Members of the T-CARE consortium have recently established and published mouse and rat models of autoimmune limbic encephalitis and Rasmussen's encephalitis all involving T cell-driven focal immune responses in the brain. The T-CARE consortium will establish strong collaborations between epileptologists and immunologists including model transfer for validation/reproduction of the experimental findings to obtain strong reliable data from two independent labs for each model regarding the role of T cells. It will independently test the application of specialized anti-CD3 monoclonal antibodies that have been shown to dampen autoimmune T cell responses on the clinical and paraclinical disease manifestations in a preventive and therapeutic setting. With this large data-set in 3 relevant experimental models, we will aim at further development of the approach in tight collaboration with Sanofi, the provider of Teplizumab, a recombinant monoclonal anti-CD3 antibody already approved for children and adults with T cell-mediated type 1 diabetes (T1D) and conduct proof-of-concept clinical trials in autoimmune limbic encephalitis and Rasmussen's encephalitis.

• DFG Programme: Research Grants
• International Connection: Ireland, Italy, Switzerland, Turkey
• Cooperation Partners: Professorin Dr. Nihan Carcak; Professorin Dr. Francesca Colciaghi; Dr. Massimo Constanza; Dr. Marco de Curtis; Dr. Kristof Egervari; Professor Dr. Chris Greene; Professor Dr. David Henshall; Professor Dr. Doron Merkler; Professor Dr. Erdem Tüzün