Fig. 1

MAC inhibitor prevents relapse whereas, inhibitor of C5aR1-mediated inflammation ameliorates disability. Scheme illustrating inhibition of the terminal complement pathway a. at the level of C5b-C9 (MAC) by antisense targeting of complement C6 mRNA (C6 antisense, 5 mg/kg), b. at the level of C5aR-mediated inflammation by an antagonist of C5aR1 (PMX205, 1.5 mg/kg) (a). Clinical scores of mice with chronic relapsing EAE receiving C6 antisense (n = 13, in red) or PMX205 (n = 10, in green) or no drug (n = 17, in blue). The C6 antisense-treated mice did not show relapse or neurological deterioration post-relapse phase. In contrast, PMX205 did not stop progression of neurological disability completely. Differences between groups were analyzed by using the Kruskal-Wallis test by ranks. Data represent the average clinical scores (mean) ± SEM. Statistical differences are indicated (**p < 0.01, ****p < 0.0001). RL, relapse; RM, remission; ns, not significant (b). Heatmap showing Ingenuity Pathway Analysis (IPA) canonical immune pathways induced by EAE and significantly affected by treatment with the C6 antisense or the PMX205 inhibitor. Pathways are ranked according to the z-score that predicts activation (orange) /suppression (blue). PMX205 is a less efficient inhibitor of neuroinflammation compared with the C6 antisense. Data were obtained from RNA-seq of mouse spinal cords collected at relapse (3 mice/group) (c)