Neuroscience 2022 – Spinal Cord Injury
San Diego, California (USA)
NX210c: subcommissural organ-spondin-derived peptide enhances behavioural functional recovery and tissue preservation in cervical traumatic spinal cord injury
N. PUNJANI1,2, S. LEMARCHANT3, S. ALTAMENTOVA1, J. CHIO1,2, J. WANG1, Y. GODFRIN3,4, M. G. FEHLINGS1,5;1
Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Canada; 2Institute of Medical Science, University of Toronto, Toronto, Canada;3Axoltis Pharma, Lyon, France;4Godfrin Life-Sciences, Caluire-et-Cuire, France;5Division of Neurosurgery and Department of Surgery, University of Toronto, Toronto, Canada
Initial physical trauma in spinal cord injury (SCI) is followed by secondary cascades which involve further cell death in the central nervous system and scar formation. Clinically, the highest incidence of traumatic SCI occurs at the cervical level, often with more severe sensorimotor deficits. NX210c is a 12-amino acid peptide derived from conserved thrombospondin type 1 repeat sequences in the subcommissural organ-spondin, which has a unique multifunctional mechanism of action to ameliorate outcomes following neurological injuries. The aim of this study was to evaluate the efficacy of NX210c to promote functional recovery and tissue repair in a cervical traumatic SCI model. Adult female Wistar rats were subjected to a C6/C7 clip compression-contusion injury and treated once daily with intraperitoneal injections of NX210c (8 mg/kg) or its vehicle beginning 4h or 8h post-injury (n=16-17/group). Uninjured sham rats (n=12) received a laminectomy with vehicle treatment beginning at 4h post-injury. Neurobehavioral tests were performed for up to 8 weeks post-injury, and rats were then sacrificed for histological assessments. Early administration of NX210c at 4h increased forelimb grip strength at 3, 4, 7 and 8 weeks post-injury (p<0.05) and improved several static and dynamic aspects of locomotion including interlimb coordination, (i.e., regularity index or base of support of the forelimbs; CatWalk). When delaying first administration to 8h post-injury, NX210c promoted weight gain, accelerated bladder control recovery from 14 to 9 days post-injury, and improved trunk balance (inclined plane) as early as one-week post-injury (p<0.05). Regardless of the therapeutic window, more SCI rats with weight support were observed following NX210c treatment, however a higher percentage of rats with weight support were observed at the delayed injection timepoint, 94% compared to 75% of corresponding vehicle rats, at 8 weeks post-injury. For skilled reaching (Montoya test), higher accuracy for successful reaching of pellets was observed with delayed injection at weeks 6 and 8 post-injury (p>0.05). Using histology (n=6/group) we demonstrate greater white matter preservation and reduced cavity size at the injury epicenter when NX210c treatment is started 8h post-injury compared to vehicle controls (p<0.05). NX210c provides a multi-faceted approach that mitigates various aspects of SCI, improving motor function, bladder control, and white matter preservation, with more benefits observed at the later initial injection timepoint. We anticipate that this study will provide a strong proof of concept for the use of NX210c as a treatment for acute cervical SCI patients.