Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury

Martin Oudega, Owen Y. Chao, Donna L. Avison, Roderick T. Bronson, William J. Buchser, Andres Hurtado, Barbara Grimpe

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

After spinal cord injury, proteoglycans with growth-inhibitory glycosaminoglycan (GAG-) side chains in scar tissue limit spontaneous axonal sprouting/regeneration. Interventions that reduce scar-related inhibition facilitate an axonal growth response and possibly plasticity-based spinal cord repair. Xylosyltransferase-1 (XT-1) is the enzyme that initiates GAG-chain formation. We investigated whether intravenous administration of a deoxyribozyme (DNA enzyme) to XT-1 mRNA (DNAXT-1as) would elicit plasticity after a clinically relevant contusion of the spinal cord in adult rats. Our data showed that systemic DNAXT-1as administration resulted in a significant increase in sensorimotor function and serotonergic axon presence caudal to the injury. DNAXT1as treatment did not cause pathological or toxicological side effects. Importantly, intravenous delivery of DNAXT-1as did not exacerbate contusion-induced neuropathic pain. Collectively, our data demonstrate that DNAXT-1as is a safe neurotherapeutic, which holds promise to become an integral component of therapies that aim to improve the quality of life of persons with spinal cord injury.

Original languageEnglish
Pages (from-to)170-179
Number of pages10
JournalExperimental Neurology
Volume237
Issue number1
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Keywords

  • Chondroitin sulfate proteoglycans
  • DNA enzyme
  • Functional recovery
  • Glial scar
  • Neurotherapeutics
  • Regeneration
  • Spinal cord injury

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