Life after cerovive: a personal perspective on ischemic neuroprotection in the post-NXY-059 era - PubMed (original) (raw)
Review
. 2007 Jun;38(6):1967-72.
doi: 10.1161/STROKEAHA.106.479170. Epub 2007 May 3.
Affiliations
- PMID: 17478741
- DOI: 10.1161/STROKEAHA.106.479170
Review
Life after cerovive: a personal perspective on ischemic neuroprotection in the post-NXY-059 era
Myron D Ginsberg. Stroke. 2007 Jun.
Abstract
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.
Comment in
- Issues pertaining to the critiques of the SAINT-I Trial.
Fisher M, Hess DC, Lees K. Fisher M, et al. Stroke. 2007 Nov;38(11):e126-7; author reply e128. doi: 10.1161/01.STROKEAHA.107.500819. Stroke. 2007. PMID: 17968005 No abstract available.
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