Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury.
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.
Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. moudega@pitt.edu
Martin
M
Oudega
Owen Y
OY
Chao
Donna L
DL
Avison
Roderick T
RT
Bronson
William J
WJ
Buchser
Andres
A
Hurtado
Barbara
B
Grimpe
D000818:Animals; D021881:DNA, Catalytic / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D005260:Female; D007275:Injections, Intravenous; D010430:Pentosyltransferases / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D012333:RNA, Messenger / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000235:genetics; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D000097608:UDP Xylose-Protein Xylosyltransferase
D021881:DNA, Catalytic; D010430:Pentosyltransferases; D012333:RNA, Messenger; D000097608:UDP Xylose-Protein Xylosyltransferase