Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury
Journal
Experimental Neurology
Series/Report No.
Experimental Neurology
Journal Volume
237
Journal Issue
1
Start Page
170-179
ISSN
0014-4886
Date Issued
2012-09
Author(s)
Oudega, Martin
Avison, Donna L.
Bronson, Roderick T.
Buchser, William J.
Hurtado, Andres
Grimpe, Barbara
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.
SDGs
Publisher
Elsevier BV
Type
journal article