Figure 1.
FTY720 efficacy in DA rat model of chronic‐protracted EAE, actively induced by syngeneic neuroantigens. Data are shown as mean clinical score ± SEM. All animals developed full hind limb paralysis by day 12 and continued to show strong neurologic deficits by the initiation of treatment on days 12 and 40. In contrast with vehicle (▪), oral FTY720 at 0.3 mg/kg completely prevented onset of EAE symptoms upon prophylactic treatment (□). FTY720 0.3 mg/kg therapeutic dosing (○) from days 12 to 28 rapidly and fully curtailed further development of EAE symptoms. Even more importantly, FTY720 rescue therapy at 0.3 mg/kg (◊) from days 40 to 53 significantly reversed neurological impairment to a deficit in tail tonus. On days 11 and 29 (▴ along x‐axis), rats were sacrificed for real‐time PCR (n = 6 per group, including naïve rats). On days 40 and 54 (▵ along x‐axis), animals were sacrificed for neuropathology (n = 6 per group) as shown in 8, 9. Level of significance between the vehicle and FTY720 groups was determined by one‐way ANOVA of area‐under‐the‐curve values from days 0–11, 12–29 and 40–54 for the prophylactic, therapeutic and rescue therapy arms, respectively, followed by a post‐hoc Tukey test. ***P ≤ 0.001. Abbreviations: FTY720 = fingolimod; DA = Dark Agouti; EAE = experimental autoimmune encephalomyelitis; SEM = standard error of mean; PCR = polymerase chain reaction; ANOVA = analysis of variance.