A trial of Ebselen PZ51, a selenoorganic compound with glutathione peroxidase-like action, is currently in phase III of clinical trial. A small, randomized, double-blind, placebo-controlled trial of Ebselen initiated within 48 hours after stroke suggested protective efficacy as measured by the Glascow Outcome Scale (GOS) and Barthel Index (BI) at 1 month (p = 0.023), but not at 3 months (p = 0.056). Better clinical outcomes were observed if Ebselen administration was initiated less than 24 hours after symptom onset, but not greater than 24 hours.19 The Edaravone Acute Infarction Study (EAIS), a double-blind, randomized, placebo-controlled study looking at the effect of Edaravone (MCI-186) administered within 72 hours after ischemic stroke onset, yielded promising results (modified Rankin Scale [mRS] score significantly improved; p = 0.0382).20 The agent has been clinically available in Japan since 2001; however, it has not been followed up with either further study or clinical usage in the United States. A recent Japanese study of Edaravone in cardioembolic stroke suggested it may only be useful in patients with mild stroke (National Institutes of Health Stroke Scale (NIHSS) score < 8); however, the trend toward long-term function seemed not to favor Edaravone.21
Metal cations play a key role in free radical propagation and endothelial and lipid injury. Deferoxamine, an iron chelator, is under phase I investigation as a neuropro-tectant after acute stroke. Because iron is the catalyst of the Fenton cycle, deferoxamine-iron binding could act as an indirect free-radical scavenger. Additionally, deferoxamine is thought to stabilize hypoxia-inducible factor-1 (HIF-1), one of the transcription factors that increases the expression of erythropoietin and vascular endothelial growth factor. In a rat model of middle cerebral artery (MCA) stroke, deferoxamine administration as late as 24 hours after stroke onset has been shown to reduce infarct volume by as much as 28% and to improve functional recovery.22 DP-b99 is a lipophilic membrane-activated metal cation chelator. It has been shown to be safe in humans and has entered a phase IIb trial, looking at neuroprotective effects when administered within 9 hours of stroke.23
Was this article helpful?