title: Human Data Supporting Glyburide in Ischemic Stroke.
abstract: The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. An early phase II study using magnetic resonance imaging and plasma biomarkers supports the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase II study and definitive efficacy studies are needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative.
authors.affiliation: Division of Neurocritical Care and Emergency Neurology, Yale University School of Medicine, 15 York Street, LCI 10th Floor, New Haven, CT, 06520, USA. kevin.sheth@yale.edu.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Sheth
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.affiliation: Department of Public Health Sciences, Medical School of South Carolina, Charleston, SC, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Elm
authors.affiliation: Department of Neurology, Charité Hospital, Berlin, Germany.
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
authors.affiliation: Department of Neurology, Charité Hospital, Berlin, Germany.
authors.forename: Hagen
authors.initials: H
authors.lastname: Kunte
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: W Taylor
authors.initials: WT
authors.lastname: Kimberly
mesh_terms: D001929:Brain Edema / Q000000981:diagnostic imaging / Q000517:prevention & control*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D020300:Intracranial Hemorrhages / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D007004:Hypoglycemic Agents; D010959:Tissue Plasminogen Activator; D005905:Glyburide