Targeting SOX9 to alter scar gene expression and promote regeneration after spinal cord injury

Funding Details
Canadian Institutes of Health Research
  • Grant type: Operating Grant
  • Years: 2010/11 to 2012/13
  • Total Funding: $469,473
Keywords
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Project Summary

Spinal cord injury (SCI) is a catastrophic event that is a major health care issue, causing lifelong disability. In the USA and Canada, more than 12,000 spinal cord injuries occur annually, and ~275,000 people live with permanent, serious disabilities due to SCI (Cdn. Paraplegic Assoc.). Since SCI usually occurs in young males it represents a lifelong burden to the patient and a socioeconomic challenge to our society. It has been estimated that the impact of neurotrauma is one of the single most costly occurrences in Ontario's health system (Ontario Neurotrauma Foundation). Currently, there are no effective treatments for SCI. Improving recovery and regeneration after SCI will relieve pressure on our healthcare system and produce priceless improvements to the quality of life of SCI patients. The absence of regeneration after spinal cord injury (SCI) has been attributed to the molecular makeup of the scar that inhibits nerve growth. Astrocytes (the major cell tpe that produces the scar) receive a variety of signals after injury and respond by producing scar proteins, some of which inhibit regeneration and some of which can promote regeneration. We have identified a protein called SOX9 that up-regulates the expression of anti-regenerative molecules and down-regulates the expression of pro-regenerative molecules in astrocytes in the injured spinal cord. Thus inhibiton of SOX9 should increase the expression of pro-regenerative genes and decrease the expression of anti-regenerative genes. This application seeks support to further our understanding of how SOX9 works with other proteins to regulate gene expression and to test whether SOX9 inhibition improves regeneration after SCI.