Spinal Cord Injury: Clinical Trials and Translational Tribulations

Spinal Cord Injury (SCI) is a common cause of neurological morbidity and mortality, particularly affecting young adults. The effect on an individual and his or her family can be devastating. The prevalence of SCI in Canada and the US is estimated at 1.4 million cases with an annual incidence of 13,000. The Pathophysiology of SCI is a complex interaction of inflammation, vascular insult, glial scarring and cell death, dysfunction and regeneration. Despite a growing wealth of pre-clinical scientific knowledge and understanding, there has been only minimal clinical benefit shown in a few human trials. In this chapter we provide an in-depth review of clinical trials in SCI identifying concurrent novel, on-going trials and highlight the hopes for the future. The chapter will focus on the key historical trials of methylprednisolone, GM-1 and thyrotrophin-releasing hormone and then discuss the potential of ion-channel blockers, targeted therapeutics and monoclonal antibodies. Further discussion focuses on endocrine and immunomodulation and injectable biomaterials. The experiences of human SCI stem cell trials are analysed and the novel therapeutic target of central pattern gait generator stimulation in neuro-rehabilitation is proposed.

Keywords: Spinal cord injury, clinical trials, therapeutic targets, NASCIS, hydrogels, self-assembling peptides, HAMC, stem cells, Geron, timing of surgery, immunomodulation, prevention, GM-1, thyrotrophin-releasing hormone.