Found in translation: The rationale behind the early development of glibenclamide in large hemispheric infarction

Abstract

Many reasons have been put forth to explain the inability to translate neuroprotection in animal stroke models to humans. Following our determination that glibenclamide is an anti-edema drug, not a neuroprotective drug, and the revelation that the "gold standard" middle cerebral artery occlusion used for animal studies models large hemispheric infarction, a subpopulation of ischemic stroke that develops clinically relevant edema that contributes significantly to poor outcomes, we designed an innovative approach to studying the drug in patients with large hemispheric infarction. The approach included careful selection of the relevant patient population, which gave us a high degree of confidence to move forward into humans. Initial human studies showed drug effects consistent with the animal studies. The considerations leading to the development plan are described.

Keywords: Glibenclamide; Glyburide; Ischemic stroke; Large hemispheric infarction; Malignant cerebral edema; Malignant middle cerebral artery infarction; Middle cerebral artery occlusion model; Stroke therapy academic industry roundtable.