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

  title={Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury},
  author={Martin Oudega and Owen Yuan-Hsin Chao and Donna L. Avison and Roderick T Bronson and William J. Buchser and Andr{\'e}s Hurtado and Barbara Grimpe},
  journal={Experimental Neurology},
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… 
Long term study of deoxyribozyme administration to XT-1 mRNA promotes corticospinal tract regeneration and improves behavioral outcome after spinal cord injury
A potential therapeutic to reduce the presence of proteoglycans at the injury site after acutely traumatizing the spinal cord of rats is developed with the aid of a DNA enzyme against the mRNA of xylosyltransferase-1 (DNAXT-1as).
Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury
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Developing an astrocyte-selective AAV-ADAMTS4 gene therapy to promote repair after spinal cord injury
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Receptors of Chondroitin Sulfate Proteoglycans and CNS Repair
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Molecular mechanisms of scar-sourced axon growth inhibitors
Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries.
Anti-Chondroitin Sulfate Proteoglycan Strategies in Spinal Cord Injury: Temporal and Spatial Considerations Explain the Balance between Neuroplasticity and Neuroprotection
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Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses
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Polymer-Based Scaffold Strategies for Spinal Cord Repair and Regeneration
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A better understanding of the molecules and molecular pathways underlying the remarkable individualism among neurons in mature zebrafish may support the development of therapies for SCI and their translation to the clinic.
Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem
Combinational strategies have demonstrated greater beneficial outcomes than their individual components alone by addressing multiple aspects of SCI pathology, and clinical trial designs in the future will eventually also need to align with this notion.


Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord.
Treatment with a deoxyribozyme against XT-1 mRNA decreased the amount of glycosylated PGs and promoted axon growth through scar tissue in the injured spinal cord, and may become a contributing factor in spinal cord repair strategies.
A Novel DNA Enzyme Reduces Glycosaminoglycan Chains in the Glial Scar and Allows Microtransplanted Dorsal Root Ganglia Axons to Regenerate beyond Lesions in the Spinal Cord
The experiments demonstrate the critical role of PGs, and particularly those in the penumbra, in causing regeneration failure in the adult spinal cord.
Single, high-dose intraspinal injection of chondroitinase reduces glycosaminoglycans in injured spinal cord and promotes corticospinal axonal regrowth after hemisection but not contusion.
It is proposed that improved axonal growth in hemisected spinal cords is due to decreased inhibition resulting from degradation of CSPGs located adjacent to severed CST axons, suggesting that other inhibitors of axonalgrowth persist in the gliotic regions.
Chondroitinase ABC Digestion of the Perineuronal Net Promotes Functional Collateral Sprouting in the Cuneate Nucleus after Cervical Spinal Cord Injury
Results demonstrate, for the first time, a functional change directly linked to anatomical evidence of sprouting by spinal cord afferents after chABC treatment, in the chABC-treated rats.
Manipulating the glial scar: Chondroitinase ABC as a therapy for spinal cord injury
There is robust pre-clinical evidence demonstrating beneficial effects of Ch ABC treatment following spinal cord injury, and these effects have been replicated in a number of different injury models, with independent confirmation by different laboratories, providing an important validation of ChABC as a promising therapeutic strategy.
Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury
Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC
Chondroitinase ABC Promotes Sprouting of Intact and Injured Spinal Systems after Spinal Cord Injury
Robust sprouting is found of both injured and intact descending projections as well as uninjured primary afferents after a cervical dorsal column injury and ChABC treatment and CSPG degradation; compensatory sprouting of descending systems could be a key mechanism underlying functional recovery.
The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury
Combined glial fibrillary acidic protein (GFAP) immunohistochemistry and in situ hybridization demonstrated that GFAP astrocytes constituted a source of neurocan production after spinal cord injury, establishing a CSPG-rich matrix that persists for up to 2 months following injury.
Inhibiting Glycosaminoglycan Chain Polymerization Decreases the Inhibitory Activity of Astrocyte-Derived Chondroitin Sulfate Proteoglycans
Data indicate that targeting the biosynthesis of CSPG GAG is a potentially new therapeutic avenue for decreasing CSPg GAG produced by astrocytes after CNS injury.
Self‐assembling peptide amphiphile promotes plasticity of serotonergic fibers following spinal cord injury
Injection into the injured spinal cord of peptide amphiphile (PA) molecules that self‐assemble and display the laminin epitope IKVAV at high density improved functional recovery after spinal cord