Preclinical studies towards treatments for spinal cord injury
Preclinical Studies Towards Treatments For Spinal Cord Injury
Wolfram Tetzlaff MD. PhD, International Collaboration on Repair Discoveries (ICORD), Departments of Zoology and Surgery, University of British Columbia The objective of my presentation will be to provide a brief review of animal based research and of human clinical trials of treatments for spinal cord injury. Several problems and obstacles stand in the way of functional recovery after spinal cord injury. While most human injuries do not entail a complete severance of the spinal cord, secondary damage and inflammation in the early days after injury enlarge the site of primary injury and lead to further tissue loss and deterioration of function. Hence, protection of the spinal cord tissue is an immediate research goal (neuroprotection). This secondary damage also leads to a loss of myelin, i.e. the insulators around nerve fibres, leading to functional failure of nerve impulse conduction. Moreover, the injured adult spinal cord itself is not a favorable environment for re-growth of severed nerve fibres and various molecules inhibit regeneration across the spinal cord injury site. To this date only one drug, methylprednisolone, has been approved for the acute treatment of human spinal cord injury, yet its neuroprotective efficacy is marginal and its safety debated. I will briefly review recent discoveries of neuroprotective regimen in the injured animal spinal cord using clinically used drugs. In our own laboratories, we found beneficial effects of MINOCIN, a clinically used tetracycline derivative, when administered within 3 hours after injury. Clinical trials of MINOCIN are currently under way in Calgary and a brief update on this trial and other trials in human spinal cord injury will be provided. In addition, our rodent data indicate’s that a dietary restriction regimen has significant neuroprotective effects and could become an adjuvant in future treatments.
While neuroprotective strategies target the immediate injury scenario, basic spinal cord injury research is also focusing on repair strategies. A plethora of obstacles prevent regeneration of the injured spinal cord and these will be briefly reviewed. They include the formation of -a glial scar at the site of injury, the expression of inhibitors of axonal regeneration and the weak regenerative response of the nerve cells in the injured spinal cord. Combinatorial treatment strategies seem to be required to overcome these obstacles, and often these include cell grafts. Transplantations of “stem cells or embryonic” into humans with spinal cord injury are performed in some countries (e.g. China) and have recently gained much media attention. I will briefly address critical issues with these clinical applications, and present some of our findings in animals using skin-derived cells which promote myelin formation and nerve fibre regrowth. The basic requirements for clinical trials will be discussed. Our work is supported by the Canadian Institutes for Health Research, NeuroScience Canada, Canadian Foundation for Innovation, Spinal Research – United Kingdom, the Christopher Reeve Paralysis Foundation (USA) and the British Columbia Neurotrauma Foundation.
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