Administration of a Novel Peptide Derived From Thrombospondin Repeat Sequences Enhances Recovery after Cervical Spinal Cord Injury

Spinal cord injury (SCI) is a debilitating condition resulting in the loss of sensorimotor functioning at and below the site of injury. Despite advances in the treatment and management of SCI, there are no current approved pharmacological therapies to augment motor function and functional recovery. NX210c is a 12-amino acid peptide derived from thrombospondin type 1 (TSP1) repeat sequences from the subcommissural organ-spondin protein. TSPs are glycoproteins present in the extracellular matrix, mediating cell-cell and cell-matrix interactions and axon pathfinding. NX210c was previously shown to improve axonal regeneration and functional recovery in thoracic SCI. The aim of this study was to evaluate the ability of NX210c to promote functional recovery and tissue repair in a traumatic cervical SCI rat model. Adult female Wistar rats were subjected to a C6/C7 bilateral clip compression-contusion injury and treated once daily with intraperitoneal injections of NX210c (8 mg/kg) or its vehicle for 8 weeks, beginning 4 h or 8 h post-injury. Administration of NX210c beginning at 4 h post-injury increased forelimb grip strength post-injury and improved several static and dynamic aspects of locomotion, including interlimb coordination. When the first administration was undertaken at 8 h post-injury, NX210c promoted weight gain, improved trunk balance (inclined plane), trended toward accelerated bladder control recovery, and approached significance for skilled reaching at 8 weeks post-injury. Furthermore, for animals that were treated daily with NX210c starting 8 h post-injury, histological analysis demonstrated greater white and gray matter preservation and reduced cavity size, along with the upregulation of neuronal markers. To conclude, NX210c mitigates various aspects of SCI, including motor function and tissue preservation, with preferential results being obtained with the delayed initial administration of NX210c at 8 h post-injury.