Investigating the role of SOX9 in recovery from spinal cord injury

Funding Details
Canadian Institutes of Health Research
  • Grant type: Operating Grant
  • Years: 2014/15 to 2018/19
  • Total Funding: $655,672
Keywords
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Project Summary

There are currently no therapies to treat spinal cord injury. We have focused on designing strategies that enhance the body's normal reparative responses to spinal cord injury. One such natural response to spinal cord injury is to rewire spinal cord circuits to regain lost function. A second natural response to spinal cord injury is to activate neural stem cell proliferation and differentiation. We have identified a protein, SOX9, as an ideal target for spinal cord injury therapies. We have shown that SOX9 is responsible for driving the expression of nerve repelling molecules in the injured spinal cord. These molecules block nerve growth that might improve function after injury. SOX9 also promotes neural stem cells activated by injury to generate support cells in the nervous system instead of neurons. Thus we predicted that blocking SOX9 could lead to improved outcomes after spinal cord injury by decreasing the levels of nerve repelling proteins and/or by decreasing the generation of support cells and increasing the generation of new neurons in the injured spinal cord. Using a line of transgenic mice we have demonstrated that blocking SOX9 improves recovery in a mouse model of spinal cord injury. This application seeks to test whether blocking SOX9 improves recovery from spinal cord injury in mice by its effects on the expression of nerve repelling molecules or by its effects on neural stem cells. Finally this application also seeks support to test the effects of a peptide and a small molecule designed to block SOX9 activity on recovery from spinal cord injury.