Printed Poster | Session 1
001 – DRUG REPURPOSING: HIGH DOSE HUMAN IMMUNOGLOBULIN G FOR TREATENT OF TRAUMATIC CERVICAL SPINAL CORD INJURY
Jonathon Chon Teng Chio (1) – Jian Wang (2) – Anna Badner (3) – James Hong (1) – Vithushan Surendran (2) – Michael Fehlings (1)
Institute of Medical Science, University of Toronto, Toronto, Canada (1) – Krembil Research Institute, Toronto Western Hospital, Toronto, Canada (2) – Sue and Bill Gross Stem Cell Research Centre, University of California Irvine, Irvine, Canada (3)
Purpose and hypothesis: Neuroinflammation exacerbate damage caused by initial trauma from spinal cord injury (SCI). Severity of neuroinflammation depends on integrity of the blood-spinal cord-barrier (BSCB), as a compromised BSCB enhances neuroinflammation by facilitating immune cell infiltration. By targeting neuroinflammation, immunosuppressants are used to treat SCI patients. However, as patients experience immune suppression, immunomodulation is more effective than immunosuppression. Human Immunoglobulin G (hIgG) is used in clinic as an immunomodulatory treatment for inflammatory disorders. Although we have shown that administration of hIgG (0.4g/kg) is beneficial after SCI, the optimal dose and mechanism of hIgG are unknown. It is hypothesized that hIgG stabilizes the BSCB; reducing leukocyte infiltration, yielding long-term functional recovery and tissue preservation.
Methods: With a clinically-relevant rat model of SCI, hIgG (0.02, 0.2, 0.4, 1, 2g/kg), methylprednisolone (0.03g//kg) or vehicle was administered intravenously at 15 minutes post-SCI. Spinal cord and serum were collected to evaluate hIgG’s short and long-term effects.
Results: hIgG co-localized with BSCB. At 24 hours post-SCI, relative to hIgG (0.4g/kg) and vehicle control, hIgG (2g/kg) significantly enhanced BSCB integrity. This was associated with reduced spinal cord neuroinflammation. Intriguingly, hIgG (2g/kg) increased serum levels of inflammatory cytokines, antagonized binding ligands that facilitate immune cell infiltration into spinal cord and directed these cells to the spleen. Short term benefits of hIgG (2g/kg) correlate with enhanced tissue preservation, blood flow and functional recovery at six weeks post-injury.
Conclusion: As a clinically-relevant immunomodulatory treatment, hIgG (2g/kg) can improve health of patients. hIgG alleviates neuroinflammation without increasing immune suppression.