Pharmacological evaluation of TAK-828F, a novel orally available RORγt inverse agonist, on murine chronic experimental autoimmune encephalomyelitis model

• Published in: Journal of neuroimmunology 2019-10, Vol.335, p.577016-577016, Article 577016
• Main Authors: Nakamura, Yoshiki, Igaki, Keiko, Uga, Keiko, Shibata, Akira, Yamauchi, Hirofumi, Yamasaki, Masashi, Tsuchimori, Noboru
• Format: Article
• Language: English
• Subjects: Experimental autoimmune encephalomyelitis; TAK-828F; Th1/17; Th17
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2019.577016

We investigated the potency of TAK-828F, a RORγt inverse agonist, in murine experimental autoimmune encephalomyelitis (EAE) model. TAK-828F inhibited the differentiation of Th17 and Th1/17 cells in inguinal lymph node. Increase of these cells in central nervous system (CNS) was also inhibited by TAK-828F. Prophylactic and therapeutic treatments of TAK-828F were efficacious in the model. Plasma concentration of TAK-828F was higher than that in CNS. These results indicate that TAK-828F mainly acts at peripheral and results in the reduction of Th17- and Th1/17-dependent inflammation in CNS. Blocking RORγt may be a promising strategy for treatment of multiple sclerosis. [Display omitted] •RORγt inverse agonist, TAK-828F, suppressed Th17 and Th1/17 cells in lymph node.•TAK-828F was prophylactically and therapeutically efficacious in murine EAE model.•Increase in Th17 and Th1/17 cell in CNS tissue was inhibited by TAK-828F treatment.•Plasma concentration of TAK-828F was higher than that in spinal cord of EAE mice.•TAK-828F acts at peripheral and results in the reduction of immune reaction in CNS.