Anti-CD11d immunotherapy for CNS trauma

Funding Details
Canadian Institutes of Health Research
  • Grant type: Project Grant
  • Years: 2016/17 to 2019/20
  • Total Funding: $602,044
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Project Summary

Traumatic brain injury (TBI) and spinal cord injury (SCI) are catastrophic, giving rise to lifelong disabilities. While the primary causes of SCI and TBI may differ, they both trigger robust acute inflammatory reactions that negatively impact recovery and may lead to the development of long-term chronic inflammation and further loss of neurological function. Neuroinflammation is driven by nervous system-specific processes and compounded by the recruitment of blood-dervied pro-inflammatory cells to the lesion site. The priority of any treatment strategy must be to minimize damage to the neurons not affected by the initial trauma. The need for a neuroprotective therapy for acute brain and spinal trauma is clearly unmet. The Spinal Cord Injury Team's (SCIT) research at the Robarts Research Institute has focused on developing an anti-inflammatory neuroprotective treatment for SCI and TBI. This anti-inflammatory strategy uses an antibody to CD11d to block blood-derived pro-inflammatory cells from entering into the spinal or brain lesion. CD11d participates in the mechanism that allows blood cells to migrate into spine and brain lesions. This reduces the overall inflammation in the lesion, protects against the loss of additional neurons and increases the overall rate of neurological recovery. Our goal is to advance the CD11d antibody strategy for use in human SCI or TBI clinical trials. We now have available five candidate CD11d antibodies with anti-inflammatory activity in rats that bind to CD11d on the surface of human blood cells. To progress toward human treatment, we will determine which of these candidate antibodies promotes the best neurological recovery and prevents human blood-derived pro-inflammatory cell infiltration into a CNS lesion in appropriate rodent models. Based on these results the best CD11d antibody will be selected for a Phase I Clinical Trial in either SCI or TBI.