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(Stroke. 2007;38:1967.)
© 2007 American Heart Association, Inc.

Comments, Opinions, and Reviews

Life After Cerovive

A Personal Perspective on Ischemic Neuroprotection in the Post–NXY-059 Era

From Department of Neurology, University of Miami Miller School of Medicine, Miami, Fla.

Correspondence to Myron D. Ginsberg, MD, Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, FL 33101. E-mail mginsberg{at}med.miami.edu

The SAINT II Trial, a large randomized multicenter clinical trial of the putative neuroprotectant, NXY-059, failed to demonstrate a treatment benefit in acute ischemic stroke. The further development of this agent was suspended. The implications of this outcome are considered from several perspectives, including: (1) the marginally positive antecedent trial, SAINT I, and the critical commentary stimulated by it, which called attention to its interpretively challenging primary outcome measure—a shift in the full-scale modified Rankin scale score—and to other statistical shortcomings; (2) the cogency of the STAIR recommendations, to which the development of NXY-059 closely adhered; and (3) the inherent physiochemical shortcomings of NXY-059 as a neuroprotective agent—its polar, nonlipophilic nature, poor blood–brain barrier penetrability, nonphysiological oxidation potential, and low potency. Caution is urged, however, regarding the unwarranted adoption of a nihilistic view toward neuroprotection on the part of the stroke community in view of the abundant preclinical evidence demonstrating proof-of-principle of the feasibility of neuroprotection, as well as the multiplicity of biochemical and molecular neuroprotective targets. The author offers the personal example of a translational journey in which a promising neuroprotectant agent targeting multiple injury mechanisms, high-dose albumin therapy, has proceeded successfully from preclinical studies that established efficacy through a pilot clinical trial that demonstrated safety and offered strong suggestions of clinical efficacy, leading to a large multicenter clinical trial currently in progress.

Key Words: albumin • clinical trial • ischemia • neuroprotection • stroke

This article has been cited by other articles:

				M. Fisher, D. C. Hess, and K. Lees Issues Pertaining to the Critiques of the SAINT-I Trial Stroke, November 1, 2007; 38(11): e126 - e127. [Full Text] [PDF]

				M. D. Ginsberg Response to Letter by Fisher et al Stroke, November 1, 2007; 38(11): e128 - e128. [Full Text] [PDF]