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 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.
Ducruet
Andrew F
AF
Department of Neurological Surgery, Columbia University, New York, NY, USA.
Mocco
J
J
Mack
William J
WJ
Coon
Alexander L
AL
Marsh
Henry C
HC
Pinsky
David J
DJ
Hickman
Zachary L
ZL
Kim
Grace H
GH
Connolly
E Sander
ES
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control; D002544:Cerebral Infarction / Q000517:prevention & control; D015941:Complement Hemolytic Activity Assay / Q000662:veterinary; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D048530:Papio anubis; D011897:Random Allocation; D011951:Receptors, Complement / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000517:prevention & control*; D020521:Stroke / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1