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

J Med Primatol. 2007 Dec;36(6):375-80. doi: 10.1111/j.1600-0684.2007.00213.x.

Abstract

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 interim analysis. 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. Conclusions Further work is necessary to explain the hypotensive response observed in primates prior to further clinical development of sCR1-sLe x.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / prevention & control
  • Cerebral Infarction / prevention & control
  • Complement Hemolytic Activity Assay / veterinary
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical
  • Male
  • Neuroprotective Agents / administration & dosage*
  • Papio anubis*
  • Random Allocation
  • Receptors, Complement / administration & dosage*
  • Reperfusion Injury / prevention & control*
  • Stroke / prevention & control*
  • Time Factors
  • Treatment Outcome

Substances

  • Neuroprotective Agents
  • Receptors, Complement
  • soluble complement inhibitor 1