Fig. 1

Oral administration of IRX4204 beginning at peak disease (DPI 16) reduces clinical scores and reverses gait deficits in EAE mice. (A) Daily clinical scores from DPI 07–44 for EAE mice treated with vehicle (Veh) or IRX4204 (mean ± SEM). Relative to Veh (5 mL/kg/day, po), IRX4204 (12 mg/kg/day, po) administration beginning at peak disease (DPI 16) reduced cumulative clinical scores (insert; n = 10, one-tailed Mann-Whitney U test, P < 0.05, mean ± SEM). (B–E) Six points of the hindlimb (B) were tracked to construct a stick model for leg movements (C) during the stance (D) and swing (E) phases of a gait cycle while mice walked on a treadmill. (F–I) Gait was measured at baseline (DPI − 02) and DPI 9, 16, 23, 30, 37 and 44. EAE resulted in gait deficits by DPI 16. Relative to Veh, IRX4204 partially reversed the loss of knee average angle (F), completely normalized knee RMS differences (H) and prevented the progressive increase of ankle RMS differences (I) from DPI 30–44 (n = 10, two-way ANOVA, Šidák’s multiple comparisons test, mean ± SEM; *p < 0.05, **p < 0.01)