WFNR 2024 – Spinal Cord Injury
NX210c drug candidate peptide promotes functional recovery and repair in a rat cervical clip-compression model of spinal cord injury
Sighild Lemarchant1, Nayaab Punjani2,3, Svetlana Altamentova2, Jonathon Chio2,3, Jian Wang2, Yann Godfrin1,4, Michael G. Fehlings2,5
1Axoltis Pharma, Lyon, France
2Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Canada
3Institute of Medical Science, University of Toronto, Toronto, Canada
4Godfrin Life-Sciences, Caluire-et-Cuire, France
5Division of Neurosurgery and Department of Surgery, University of Toronto, Toronto, Canada
More than half of spinal cord injuries (SCI) occur at the cervical level, leaving patients with partial to total loss of autonomy. Regaining arm/hand and bladder functions are the most important priorities for cervical SCI patients, yet with no satisfying therapeutic solutions. NX210c is a 12-aa peptide derived from a glycoprotein involved in axonal guidance during brain development, which is under preclinical and clinical development (Axoltis Pharma). The aim of this study was to evaluate the efficacy of NX210c to promote functional recovery and tissue repair in a cervical 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 from 4h or 8h post-injury (n=16-17/group). Sham rats received a laminectomy with vehicle treatment from 4h post-injury (n=12). 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 from 3 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) from 1 week post-injury (p<0.05). Using histology (n=6/group), we demonstrate that NX210c reduced the cavity size and protected both white and gray matter when injected from 8h post-injury (p<0.05).
NX210c improves motor function, bladder control, and white matter preservation, with more benefits observed at the later initial injection timepoint. This study constitutes a strong proof of concept for the use of NX210c as an innovative treatment for patients suffering from acute SCI.