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

Publication ,  Journal Article
Blake, CM; Wang, H; Laskowitz, DT; Sullenger, BA
Published in: Oligonucleotides
February 2011

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.

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Published In

Oligonucleotides

DOI

EISSN

1557-8526

Publication Date

February 2011

Volume

21

Issue

1

Start / End Page

11 / 19

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thrombin
  • Survival Rate
  • Stroke
  • Reperfusion
  • Pharmacology & Pharmacy
  • Mice
  • Infusions, Intravenous
  • Inflammation
  • Hematoma
 

Citation

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Blake, C. M., Wang, H., Laskowitz, D. T., & Sullenger, B. A. (2011). A reversible aptamer improves outcome and safety in murine models of stroke and hemorrhage. Oligonucleotides, 21(1), 11–19. https://doi.org/10.1089/oli.2010.0262
Blake, Charlene M., Haichen Wang, Daniel T. Laskowitz, and Bruce A. Sullenger. “A reversible aptamer improves outcome and safety in murine models of stroke and hemorrhage.Oligonucleotides 21, no. 1 (February 2011): 11–19. https://doi.org/10.1089/oli.2010.0262.
Blake CM, Wang H, Laskowitz DT, Sullenger BA. A reversible aptamer improves outcome and safety in murine models of stroke and hemorrhage. Oligonucleotides. 2011 Feb;21(1):11–9.
Blake, Charlene M., et al. “A reversible aptamer improves outcome and safety in murine models of stroke and hemorrhage.Oligonucleotides, vol. 21, no. 1, Feb. 2011, pp. 11–19. Pubmed, doi:10.1089/oli.2010.0262.
Blake CM, Wang H, Laskowitz DT, Sullenger BA. A reversible aptamer improves outcome and safety in murine models of stroke and hemorrhage. Oligonucleotides. 2011 Feb;21(1):11–19.

Published In

Oligonucleotides

DOI

EISSN

1557-8526

Publication Date

February 2011

Volume

21

Issue

1

Start / End Page

11 / 19

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thrombin
  • Survival Rate
  • Stroke
  • Reperfusion
  • Pharmacology & Pharmacy
  • Mice
  • Infusions, Intravenous
  • Inflammation
  • Hematoma