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

Andrew F. Ducruet, J. Mocco, William J. Mack, Alexander L. Coon, Henry C. Marsh, David J. Pinsky, Zachary L. Hickman, Grace H. Kim, E. Sander Connolly

Research output: Contribution to journalArticle

Abstract

Background: Soluble complement receptor-1 (sCR1), a potent complement inhibitor, confers neuroprotection in a murine stroke model. Additional neuroprotective benefit is achieved by sLex -glycosylation of sCR1. In an effort to translate sCR1-sLex to clinical trials, we evaluated this agent in a primate stroke model. Methods: Adult male baboons randomly received either sCR1-sLex 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 sCR1sLex-treated groups. A hypotensive response was also observed in animals treated with sCR1-sLex. Conclusion: Further work is necessary to explain the hypotensive response observed in primates prior to further clinical development of sCR1-sLex.

Original languageEnglish (US)
Pages (from-to)375-380
Number of pages6
JournalJournal of medical primatology
Volume36
Issue number6
DOIs
StatePublished - Dec 1 2007

Keywords

  • Baboon
  • Cerebral ischemia
  • sCR1-sLe

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

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    Ducruet, A. F., Mocco, J., Mack, W. J., Coon, A. L., Marsh, H. C., Pinsky, D. J., Hickman, Z. L., Kim, G. H., & Connolly, E. S. (2007). Pre-clinical evaluation of an sLex-glycosylated complement inhibitory protein in a non-human primate model of reperfused stroke. Journal of medical primatology, 36(6), 375-380. https://doi.org/10.1111/j.1600-0684.2007.00213.x