A Robarts' Scientist has identified a target molecule that can serve as a switch between scar establishment and regenerative matrix deposition by astroctye cells.

Small molecules have been identified that can modify the activity of the gene target

BACKGROUND: Spinal cord injury (SCI) is a personally catastrophicevent that often results in disability and lifelong institutional care requirements. In the US and Canada, more than 12,000 spinal cord injuries occur annually, and ~275,000 people live with permanent, serious disabilities at an average medical cost of USD$22,000/person/year. It is estimated that 3 million people live with the consequences of spinal cord injury worldwide.  Immediately following spinal cord damage, there is an acute phase within which damage is perpetuated by an immune response and the production of cytotoxic factors that often determines the extent of debilitation.  While most therapies attempt to suppress the immunological component, an emerging therapeutic question is how to support the subsequent remodeling of the damaged area and regeneration of the spinal cord after the wound has stabilized. 

Following the acute phase, subsequent natural regeneration is often limited by the formation of the glial scar – a physical and biochemical barrier comprised of a modified CSPG.  Slow recovery is dependent upon the naturally rate limited remodeling of the glial scar and subsequent deposition of growth promoting molecules such as laminin and fibronectin.  Astrocyte cells in spinal cord injury serve the dual purpose of depositing aspects of the glial scar and supporting subsequent regeneration.  Regenerative strategies have attempted to specifically target either the breakdown of the scar itself or the deposition of growth promoting matrix.  An ideal target for augmenting the natural regenerative capacity following spinal cord injury is the cellular switch in astroctyes between the formation of scarring CSPG and establishing a growth promoting matrix. 

 

DESCRIPTION OF THE INVENTION:  A Robarts’ Scientist has identified a target molecule that can serve as a switch between scar establishment and regenerative matrix deposition by astroctye cells. By altering expression of this gene, one may disrupt the mechanism of chondroitin sulfate proteoglycan (CSPG) modification and simultaneously activate the expression and secretion of laminin and fibronectin in the scar, thus favouring regeneration following spinal cord injury or stroke .The system has been demonstrated to be valid in mouse models and serve function in human cells.

 

POTENTIAL ADVANTAGES/USES:

• Small molecules have been identified that can modify the activity of the gene target
• siRNA strategies have been successfully demonstrated
• The target gene has minimal critical background function in adulthood
• Modification of the target gene expression may be applied as an acute or chronic therapy
• Modification of the target has demonstrated to promote nerve regeneration well after injury and stabilization
• The gene is a potential therapeutic target for SCI and other forms of neurotrauma where scar formation occurs, such as brain injury and stroke
• The target may be applied in other diseases where tissue repair and recovery is inhibited by scar formation

 

Keywords: Regenerative medicine, Spinal cord injury, Stroke, Small molecule, Transcription factor, Extracellular matrix, Scar, Wound repair, Neurotrauma, Neuron, Nerve, Astrocyte, Inflammation

 

Preclinical

This technology is covered under a PCT patent application.