Treatment Groups: Oral Dose: from Days 12 to 25 | EAE Onsetb | Maximum Weight Lossc | Maximum Diseased | Cumulative Disease Score from Days 13 to 56e | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Day | % | Day | Score | Day | AUC | p vs. Vehicle | ||||
mg/kg | ||||||||||
Vehicle (n = 17) | 8.4 ± 0.4 | 23.6 ± 0.02 | 20.7 ± 0.7 | 2.9 ± 0.2 | 22.6 ± 1.5 | 79.0 ± 12.6 | ||||
FTY720, 0.03 mg (n = 8) | 8.8 ± 0.3 | 16.4 ± 0.03 | 21.9 ± 1.0 | 2.3 ± 0.4 | 28.5 ± 2.6 | 64.0 ± 14.7 | N.S. | |||
FTY720, 0.1 mg (n = 19) | 8.4 ± 0.3 | 12.0 ± 0.02 | 20.4 ± 0.2 | 1.2 ± 0.3 | 24.0 ± 1.9 | 17.0 ± 3.7 | 0.00002 | |||
FTY720, 0.3 mg (n = 19) | 9.0 ± 0.3 | 9.6 ± 0.01 | 20.2 ± 0.2 | 0.3 ± 0.1 | 24.2 ± 2.0 | 7.8 ± 2.5 | <0.00001 | |||
FTY720, 0.9 mg (n = 9) | 8.3 ± 0.2 | 15.4 ± 0.02 | 20.2 ± 0.1 | 0.6 ± 0.4 | 25.7 ± 3.7 | 7.7 ± 3.3 | 0.0005 | |||
CsA, 25 mg (n = 18) | 9.0 ± 0.3 | 16.9 ± 0.02 | 28.4 ± 2.4 | 3.3 ± 0.1 | 33.9 ± 0.6 | 52.8 ± 6.7 | N.S. |
n, number of rats per group; N.S., not significant.
↵ a Syngeneic antigen-induced EAE (Fig. 2); data shown as mean ± S.E.M.
↵ b Based on disease score ≥ 1.
↵ c Highest weight loss starting 1 week after dosing (days 20-56) compared with adjuvant control.
↵ d Initial peak of disease severity starting 1 week after dosing (days 20-56).
↵ e Level of significance (p) determined by ANOVA of AUC values for clinical scores from days 13 to 56 compared with the positive control.