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

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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