Effect of arundic acid on serum S-100β in ischemic stroke

We prospectively examined the effect of arundic acid (AA; ONO-2506) on S-100β, an astrocyte-derived protein, in a phase I acute stroke study. Subjects with acute ischemic stroke were randomized to daily infusion of AA or placebo for 7 days. Serum S-100β levels were assayed pre-infusion on Days 1-7 and post-infusion on Days 1, 3, and 7, and correlated with National Institutes of Health Stroke Scale (NIHSS). Samples were obtained from 86 subjects (46 AA, 40 placebo). Increase in S-100β protein level from baseline was less in the AA cohort than in the placebo cohort at 7 (p = 0.0471; t-test) and 12 (p = 0.0095)-hours post-infusion on Day 3. Baseline NIHSS correlated with maximal S-100β levels between Days 1 and 3 in the AA (r = 0.51; p = 0.0003) and placebo (r = 0.41; p = 0.0084) cohorts and in the pooled aggregate (n = 86; r = 0.46; p < 0.0001). The same correlations were observed between Day 10 NIHSS and Day 1-3 maximum serum S-100β levels. Treatment with AA was associated with lower serum levels of S-100β after acute ischemic stroke. Our results showing correlation between S-100β and NIHSS indicate that this protein is a clinically relevant marker of neurological deficit in acute stroke.