Figure 6
CKD-506 decreased the clinical scores in mice with experimental autoimmune encephalitis (EAE) under the therapeutic regimen. C57BL/6 (n = 9 per group for the non-immunized groups and vehicle group; n = 8 per group for the other groups) mice were orally administered CKD-506 (30 mg/kg bodyweight) and fingolimod (0.3 mg/kg bodyweight) daily from day 15 post-myelin oligodendrocyte glycoprotein35–55 immunization (a, b). The clinical score (a) and final clinical score (b) were determined. The CKD-506-treated group exhibited alleviated clinical scores even after CKD-506 discontinuation and delayed disease exacerbation after fingolimod discontinuation (c, d). Mice (n = 12 per group for FS; n = 10 per group for the other groups) were treated with CKD-506 (30 mg/kg bodyweight) and fingolimod (0.3 mg/kg bodyweight) from days 6 to 14 post-induction. Treatment was discontinued or changed from fingolimod to CKD-506 on day 15 post-induction. The clinical score (c), final clinical score (d), and the number of white blood cells in the blood (e) were evaluated. Data are presented as mean ± SD. Two-way ANOVA, followed by Bonferroni post-hoc test for (a, c); one-way ANOVA, followed by Dunnett’s post-hoc test for (b, d, e). #p < 0.05, ###p < 0.001, non-immunized groups versus vehicle group; *p < 0.05, **p < 0.01, and ***p < 0.001, drug-treated group versus vehicle group; $p < 0.05, FS versus FC. N, non-immunized groups; V, vehicle group; Fin, fingolimod-treated group; CS, CKD-506-treated group in which dosing of CKD-506 was discontinued from day 15 post-induction; FS, fingolimod-treated group in which treatment was discontinued from day 15 post-induction; FC, the group in which fingolimod was replaced with CKD-506 on day 15 post-induction; S, dosing stop; C, treatment change from fingolimod to CKD-506.
