Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke: minocycline.
There is only 1 US Food and Drug Administration-approved drug for acute ischemic stroke: tissue plasminogen activator (tPA). Due to a short time window and fear of intracerebral hemorrhage (ICH), tPA remains underutilized. There is great interest in developing combination drugs to use with tPA to improve the odds of a favorable recovery and to reduce the risk of ICH. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for ICH associated with tPA use. Minocycline is also an anti-inflammatory agent and inhibits poly (ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in the clinical trials conducted to date.
Hess
David C
DC
Department of Neurology, Medical College of Georgia, Augusta, GA, USA.
Fagan
Susan C
SC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008911:Minocycline / Q000627:therapeutic use*; D010960:Plasminogen Activators / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology
D010960:Plasminogen Activators; D020780:Matrix Metalloproteinase 9; D008911:Minocycline
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