scholarly journals Inhibiting an inhibitor: a decoy to recover dexterity after spinal cord injury

Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1618-1622
Author(s):  
Elizabeth J Bradbury ◽  
Raquel Oliveira
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nogo Receptor ◽  
Cord Injury ◽  
Human Primate

This scientific commentary refers to ‘Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury’, by Wang et al. (doi:10.1093/brain/awaa116).

scholarly journals Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury

Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1697-1713 ◽  
Author(s):  
Xingxing Wang ◽  
Tianna Zhou ◽  
George D Maynard ◽  
Pramod S Terse ◽  
William B Cafferty ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Recovery Of Function ◽  
Neurological Deficits ◽  
Vehicle Group ◽  
Post Injury ◽  
Nogo Receptor ◽  
Human Dose ◽  
Cord Injury ◽  
Human Primate

Abstract After CNS trauma such as spinal cord injury, the ability of surviving neural elements to sprout axons, reorganize neural networks and support recovery of function is severely restricted, contributing to chronic neurological deficits. Among limitations on neural recovery are myelin-associated inhibitors functioning as ligands for neuronal Nogo receptor 1 (NgR1). A soluble decoy (NgR1-Fc, AXER-204) blocks these ligands and provides a means to promote recovery of function in multiple preclinical rodent models of spinal cord injury. However, the safety and efficacy of this reagent in non-human primate spinal cord injury and its toxicological profile have not been described. Here, we provide evidence that chronic intrathecal and intravenous administration of NgR1-Fc to cynomolgus monkey and to rat are without evident toxicity at doses of 20 mg and greater every other day (≥2.0 mg/kg/day), and far greater than the projected human dose. Adult female African green monkeys underwent right C5/6 lateral hemisection with evidence of persistent disuse of the right forelimb during feeding and right hindlimb during locomotion. At 1 month post-injury, the animals were randomized to treatment with vehicle (n = 6) or 0.10–0.17 mg/kg/day of NgR1-Fc (n = 8) delivered via intrathecal lumbar catheter and osmotic minipump for 4 months. One animal was removed from the study because of surgical complications of the catheter, but no treatment-related adverse events were noted in either group. Animal behaviour was evaluated at 6–7 months post-injury, i.e. 1–2 months after treatment cessation. The use of the impaired forelimb during spontaneous feeding and the impaired hindlimb during locomotion were both significantly greater in the treatment group. Tissue collected at 7–12 months post-injury showed no significant differences in lesion size, fibrotic scar, gliosis or neuroinflammation between groups. Serotoninergic raphespinal fibres below the lesion showed no deficit, with equal density on the lesioned and intact side below the level of the injury in both groups. Corticospinal axons traced from biotin-dextran-amine injections in the left motor cortex were equally labelled across groups and reduced caudal to the injury. The NgR1-Fc group tissue exhibited a significant 2–3-fold increased corticospinal axon density in the cervical cord below the level of the injury relative to the vehicle group. The data show that NgR1-Fc does not have preclinical toxicological issues in healthy animals or safety concerns in spinal cord injury animals. Thus, it presents as a potential therapeutic for spinal cord injury with evidence for behavioural improvement and growth of injured pathways in non-human primate spinal cord injury.

scholarly journals Humane Non-Human Primate Model of Traumatic Spinal Cord Injury: Quantitative Analysis of Electromyographic Data

2015 ◽  
Vol 05 (07) ◽  
pp. 161-168
Author(s):  
Nitin Seth ◽  
Farah Masood ◽  
John B. Sledge ◽  
William A. Graham ◽  
Douglas L. Rosene ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Quantitative Analysis ◽  
Traumatic Spinal Cord Injury ◽  
Primate Model ◽  
Cord Injury ◽  
Human Primate

Rodent, large animal and non-human primate models of spinal cord injury

Zoology ◽  
2017 ◽  
Vol 123 ◽  
pp. 101-114 ◽  
Author(s):  
Raffaele Nardone ◽  
Cristina Florea ◽  
Yvonne Höller ◽  
Francesco Brigo ◽  
Viviana Versace ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Large Animal ◽  
Cord Injury ◽  
Human Primate

scholarly journals Humane Non-Human Primate Model of Traumatic Spinal Cord Injury Utilizing Electromyography as a Measure of Impairment and Recovery

2013 ◽  
Vol 03 (01) ◽  
pp. 86-89 ◽  
Author(s):  
William A. Graham ◽  
Douglas L. Rosene ◽  
Susan Westmoreland ◽  
Andrew Miller ◽  
Ervin Sejdic ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Traumatic Spinal Cord Injury ◽  
Primate Model ◽  
Cord Injury ◽  
Human Primate

scholarly journals Nogo Receptor Deletion and Multimodal Exercise Improve Distinct Aspects of Recovery in Cervical Spinal Cord Injury

2010 ◽  
Vol 27 (11) ◽  
pp. 2055-2066 ◽  
Author(s):  
Noam Y. Harel ◽  
Kang-Ho Song ◽  
Xin Tang ◽  
Stephen M. Strittmatter
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cervical Spinal Cord ◽  
Cervical Spinal Cord Injury ◽  
Nogo Receptor ◽  
Cord Injury
Sign in / Sign up

Export Citation Format

Share Document