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(Stroke. 2001;32:190.)
© 2001 American Heart Association, Inc.

Original Contributions

NXY-059, a Free Radical–Trapping Agent, Substantially Lessens the Functional Disability Resulting From Cerebral Ischemia in a Primate Species

Jonathan W. B. Marshall, PhD; Katharine J. Duffin, BA; A. Richard Green, DSc Rosalind M. Ridley, ScD

From MRC Comparative Cognition Team, Department of Experimental Psychology, University of Cambridge (UK) (J.W.B.M., K.J.D., R.M.R.); and AstraZeneca R&D Charnwood, Loughborough, UK (A.R.G.).

Correspondence to Dr Jonathan W.B. Marshall, MRC Comparative Cognition Team, Department of Experimental Psychology, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK. E-mail jwbm2{at}cus.cam.ac.uk

Background and Purpose—NXY-059 is a novel nitrone with free radical–trapping properties that has a considerable neuroprotective effect in rats. We have now examined the efficacy of this drug at reducing long-term functional disability in a primate model of stroke.

Methods—Twelve monkeys were trained and tested on a variety of behavioral tasks used to dissociate and quantify motor and spatial deficits. Five minutes after permanent occlusion of the right middle cerebral artery, monkeys received a 1-mL intravenous infusion of either saline or NXY-059 (28 mg · kg^-1), and osmotic minipumps, model 2001D, were implanted subcutaneously to provide continuous drug or saline infusion for 48 hours. Drug-filled pumps released NXY-059 at 16 mg · kg^-1 · h^-1. The monkeys were retested 3 and 10 weeks after surgery to assess functional disability. Surgery, behavioral testing, and histology were all done blinded to treatment condition.

Results—NXY-059–treated monkeys were significantly better at reaching with their hemiparetic arm than were saline-treated monkeys when retested 3 weeks (P<0.01) and 10 weeks (P<0.01) after surgery. Drug treatment also significantly lessened the degree of spatial perceptual neglect (P<0.01), a debilitating though ameliorating consequence of this infarct. NXY-059 treatment reduced the overall amount of brain damage by >50% of saline-treatment values, with similar levels of protection afforded to both white and gray matter.

Conclusions—This novel drug has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species. These findings provide considerable encouragement for the clinical development of NXY-059.

Editorial Comment

Seth P. Finklestein, MD, Guest Editor

Neurosurgical Laboratories, Stanford University, Palo Alto, California

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