Pre-clinical evaluation of an sLe^x-glycosylated complement inhibitory protein in a non-human primate model of reperfused stroke

Background: Soluble complement receptor-1 (sCR1), a potent complement inhibitor, confers neuroprotection in a murine stroke model. Additional neuroprotective benefit is achieved by sLe^x -glycosylation of sCR1. In an effort to translate sCR1-sLe^x to clinical trials, we evaluated this agent in a primate stroke model. Methods: Adult male baboons randomly received either sCR1-sLe^x or vehicle. Stroke volume was assessed on day 3, and neurological examinations were conducted daily. Complement activity (CH₅₀) was measured at 30 minute, 2, 6, 12 hour, 3, and 10 days post-ischemia. Results: The experiment was terminated prematurely following an interimanalysis. In a preliminary cohort (n = 3 per arm), infarct volume was greater in the treated animals. No difference in neurological score was found between groups. CH₅₀ levels were significantly reduced in the sCR1sLe^x-treated groups. A hypotensive response was also observed in animals treated with sCR1-sLe^x. Conclusion: Further work is necessary to explain the hypotensive response observed in primates prior to further clinical development of sCR1-sLe^x.