Treatment of immune-mediated inflammatory diseases

Immune-mediated inflammatory diseases (IMIDs) are a group of chronic and highly disabling diseases that share common inflammatory pathways. Despite an increasing therapeutic armamentarium, there is still an urgent need for novel and improved therapeutic approaches for treating immune-mediated inflammatory diseases, such as multiple sclerosis, preferably exhibiting fewer adverse side effects and an improved clinical efficacy. NMDAr (N-Methyl-D-Aspartat receptors) are glutamate-gated ion channels reported to be widely expressed in the central nervous system. NMDArs have hence triggered an intense interest as potential therapeutic drug targets. However, their intended use has been classically restricted to treatment of diseases affecting the central nervous systems associated with neuronal dysfunction or glutamate excitotoxicity. Several NMDAr antagonists were developed, including uncompetitive NMDAr antagonists binding to the NMDA ion channel and competitive antagonists acting at the agonist-binding domain on the NR2 subunits. A German university recently developed novel improved NMDA-receptor antagonists specifically binding to the NR2B subunit of the receptor with high affinity. They found that immune cells (microglia and mono-cytes/dendritic cells), involved in the pathogenesis of IMIDs such as multiple sclerosis, express the NMDA receptor. Specifically, they upregulate the NR2B subunit under inflammatory conditions. Targeting the NR2B subunit of the NMDA receptor on microglia and monocytes resulted in a marked downregulation of activation markers and cytokine expression and/or secretion. The finding was confirmed in an in vivo mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis; EAE), showing a markedly less severe progression of disease after treatment with the novel NR2B-selective compound, even if treatment was begun after symptoms had developed. Industrial partners from therapeutic industry are sought for license agreements to produce and sell the invention.