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

Document Type

Article

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.

Medical Subject Headings

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

Publication Date

12-1-2007

Publication Title

Journal of medical primatology

ISSN

0047-2565

Volume

36

Issue

6

First Page

375

Last Page

80

PubMed ID

17976043

Digital Object Identifier (DOI)

10.1111/j.1600-0684.2007.00213.x

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