Accepted for publication in PLOS One:
Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of multiple sclerosis
Sarah K. Williams 1, Olaf Maier 2, Roman Fischer 2, Richard Fairless 1, Sonja Hochmeister 3, Aleksander Stojic 1, Lara Pick 4, Doreen Haar 4, Sylvia Musiol 4, Maria Storch 3, Klaus Pfizenmaier 2, Ricarda Diem 1
1Department of Neurooncology, University Clinic Heidelberg, Im Neuenheimer Feld 400,
69120 Heidelberg, Germany,
2Institute of Cell Biology and Immunology, University Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
3Department of Neurology, Medical University of Graz, 8010 Graz, Austria and
4Department of Neurology, University of the Saarland, 66424 Homburg/Saar, Germany.
Tumour necrosis factor (TNF) is a proinflammatory cytokine that is known to regulate inflammation in a number of autoimmune diseases, including multiple sclerosis (MS). Although targeting of TNF in models of MS has been successful, the pathological role of TNF in MS remains unclear due to clinical trials where the non-selective inhibition of TNF resulted in exacerbated disease. Subsequent experiments have indicated that this may have resulted from the divergent effects of the two TNF receptors, TNFR1 and TNFR2. Here we show that the selective targeting of TNFR1 with an antagonistic antibody ameliorates symptoms of the most common animal model of MS, experimental autoimmune encephalomyelitis (EAE), when given following both a prophylactic and therapeutic treatment regime. Our results demonstrate that antagonistic TNFR1-specific antibodies may represent a therapeutic approach for the treatment of MS in the future.