Progress in Spinal Cord Research - A refined strategy for the International Spinal Research Trust

Abstract

Achieving regeneration in the central nervous system represents one of the greatest intellectual and practical challenges in neurobiology, and yet it is an absolute requirement if spinal cord injury patients are to have any hope of recovery. The mission of the International Spinal Research Trust (ISRT), established in 1980, is to raise money speci®cally for spinal research, with a view to ending the permanence of paralysis caused by spinal cord injury. This review summarises some of the major steps forward made in recent years in understanding the mechanisms involved in spinal cord injury and where these discoveries ®t in with the ISRT's overall objectives. We review approaches aimed at (1) preventing immediate adverse reactions to injury such as neuronal death and scar formation; (2) minimising inhibitory properties of the CNS environment and maximising the growth potential of damaged neurons; (3) understanding axonal guidance systems that will be required for directed outgrowth and functional reconnection; and (4) optimising the function of surviving systems. We also discuss infrastructural' prerequisites for applying knowledge gained through spinal research to the clinical condition, including basic scienti®c issues such as developing representative animal models of spinal cord injury and sensitive quantitative methods for assessing growth and functional restoration. In addition, we point out the importance of communication. The need to share knowledge between research groups is vital for advancing our understanding of injury and repair mechanisms. Equally important is the need for communication between basic scientists and clinicians which will be essential for what is the ultimate goal of the ISRT, the development of relevant treatment strategies that will prove bene®cial to the spinal injured patient. Spinal Cord (2000) 38, 449 ± 472

Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery

“…As a consequence, damage to the spinal cord results in permanent deficits, involving partial or complete paralysis and sensory loss below the level of lesion. In the last years, numerous studies have sought to understand the factors that limit spinal cord regeneration and to assess different strategies for the repair of such injuries (Ramer et al, 2000). Most experimental studies have used techniques that allow us to induce graded spinal cord injuries, such as weight drop (Allen, 1911;Basso et al, 1995), aneurysm clip (Fehlings and Tator, 1995;Joshi and Fehlings, 2002a, b), and photochemical (Prado et al, 1987) methods.…”

International spinal research trust research strategy. III: A discussion document

“…Cell-and gene-based therapies Since the last strategy review in 2000, 2 major progress has been made in the areas of cell and gene therapy. Cellbased therapy includes grafting with fully differentiated tissue such as peripheral nerves, inflammatory system cells such as activated macrophages, CNS-resident cells such as oligodendrocytes and olfactory ensheathing cells, and cell precursors such as stem cells.…”

“…Thus, the development of a mouse model of SCI had priority in the 2nd ISRT strategy document. 2 Now such models are available, the use of knockout and transgenic mice is likely to provide insights into the molecular components of SCI and repair. Fund studies that attempt to adjust the insights generated from animal models to the scale and complexity of human SCI HC1.…”

“…2 These documents established a coherent research strategy by analysing specific areas that require attention in order to achieve the overall objectives of the ISRT -to repair the damaged spinal cord and restore useful function. The strategy documents identify key areas for funding and support, which enables basic and clinical researchers to focus research proposals, and the Scientific Committee and external reviewers to judge each proposal accordingly.…”

“…2 In general, ISRT expects applications for research funding to be influenced by and to refer directly to the themes described in this strategy document, but also recognise the need to incorporate novel approaches as they are developed.…”