Charles Tator / Andrea Mothe, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Canada

Regeneration after chronic cervical injury by a combined treatment

Funded in: 2022, 2023, 2024

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Problem: Spinal cord injury produces a cascade of degenerative events
Target: Use a combination of three treatments
Goal: Examine the possibility of new nerve circuit formation and assess recovery of function
Severe traumatic spinal cord injury produces a cascade of degenerative events at the injury site and beyond including major loss of nerve cells and supporting cells, disruption of nerve pathways, and also leaves behind an inhibitory environment and cystic spaces which prevent regeneration. In this project, the researchers will use a multifaceted approach to target many of these barriers to recovery in injured rats in the chronic stage of cervical spinal cord injury which closely resembles the injuries sustained by most people. Their novel strategy is to use a combination of three treatments:
1) injection of a drug called an ampakine which changes the entrance of calcium into cells to support their survival
2) injection of an antibody which blocks an inhibitory protein in nerve cells that blocks regeneration.
3) transplantation of human neural stem cells to fill the cysts with new nerve cells that can reconnect with uninjured nerve cells in other areas of the spinal cord.
Neural stem cell transplantation can replace host cells, restore the important covering of damaged nerve fibers and provide support for repair. The scientists will use the drug and antibody treatments to enhance the survival, differentiation, and integration of the transplanted cells with host cells to facilitate the formation of nerve circuits and connections. These treatments have individually shown promising results in studies of spinal cord injury and have been safely used in human trials of other conditions but have not been examined in combination in experimental spinal cord injury or in any human condition. Using a cervical spinal cord injury model the researchers will examine the possibility of new nerve circuit formation and assess recovery of function to both the upper and lower limbs.