A reversible aptamer improves outcome and safety in murine models of stroke and hemorrhage.

Published

Journal Article

Treatment of acute ischemic stroke with intravenous tissue-type plasminogen activator is underutilized partly due to the risk of life-threatening hemorrhage. In response to the clinical need for safer stroke therapy, we explored using an aptamer-based therapeutic strategy to promote cerebral reperfusion in a murine model of ischemic stroke. Aptamers are nucleic acid ligands that bind to their targets with high affinity and specificity, and can be rapidly reversed with an antidote. Here we show that a Factor IXa aptamer administered intravenously after 60 minutes of cerebral ischemia and reperfusion improved neurological function and was associated with reduced thrombin generation and decreased inflammation. Moreover, when the aptamer was administered in the setting of intracranial hemorrhage, treatment with its specific antidote reduced hematoma volume and improved survival. The ability to rapidly reverse a pharmacologic agent that improves neurological function after ischemic stroke should intracranial hemorrhage arise indicates that aptamer-antidote pairs may represent a novel, safer approach to treatment of stroke.

Full Text

Duke Authors

Cited Authors

  • Blake, CM; Wang, H; Laskowitz, DT; Sullenger, BA

Published Date

  • February 2011

Published In

Volume / Issue

  • 21 / 1

Start / End Page

  • 11 - 19

PubMed ID

  • 21142878

Pubmed Central ID

  • 21142878

Electronic International Standard Serial Number (EISSN)

  • 1557-8526

Digital Object Identifier (DOI)

  • 10.1089/oli.2010.0262

Language

  • eng

Conference Location

  • United States