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(Stroke. 2006;37:2649.)
© 2006 American Heart Association, Inc.

Emerging Therapies

NXY-059

A Hopeful Sign in the Treatment of Stroke

From the Department of Neurology, Medical College of Georgia, Augusta, Ga.

Correspondence to David C. Hess, MD, Department of Neurology, Medical College of Georgia, Augusta, GA. E-mail dhess@mail.mcg.edu

Marc Fisher MD Kennedy Lees MD Section Editors

Key Words: neuroprotectants

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The SAINT I trial published in the February 9, 2006 issue of the New England Journal of Medicine represents the first "positive" neuroprotective trial in stroke.¹ This breaks a long string of "neuroprotective" failures and indicates some hope for stroke treatment.² Is NXY-059 a better drug than previous failed agents or was the trial just better designed? Probably both.

NXY-059 is the first agent that fulfilled all the Stroke Therapy Academic Industry Roundtable (STAIR) recommendations regarding preclinical development before it entered a large phase-III clinical trial in stroke.³ The preclinical data with NXY-059 were robust and impressive. NXY-059 was effective at both reducing infarct size and improving functional outcome in both temporary and permanent rodent middle cerebral artery (MCA) occlusion models.^4,5 There was a clear dose response and the therapeutic window extended out to 4 hours.⁵ Next, NXY-059 was tested in a nonhuman primate model, albeit the lissencephalic marmoset.^6,7 Again, NXY-059 both reduced infarct size and improved long-term (10-week) functional outcome (reduced neglect and improved arm function) with a 4-hour window in a permanent MCA occlusion model.⁷ The reduction in infarct size and functional improvement was better than that observed with other neuroprotective agents (the GABA mimetic agent, clomethiazole and the NMDA antagonist, AR-R15896AR) in the same primate model.⁸ Importantly, the neuroprotective NXY-059 plasma levels in primates (200 µmol/L) are achievable and safe in humans and even below the target concentrations of 260 µmol/ in SAINT I.⁷

The trial design was also improved over past neuroprotective trials. First, the primary . . . [Full Text of this Article]

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