The translational dialogue in spinal cord injury research

Abstract

Background: Although the emphasis in clinical spinal cord injury (SCI) research has been directed towards the evaluation of clinical assessments (standards in neurological examination) and the appreciation of outcome measures (that is, extent and pattern of clinical recovery from SCI), the underlying neurological mechanisms for recovery from SCI are not well documented in humans. However, to improve the translational research, a meaningful preclinical-clinical dialogue is required, with an appreciation for both fundamental neural mechanisms and what makes human SCI unique. This holds true both for potential interventions in rehabilitation and novel drug or cell-based treatment approaches in acute SCI. Objectives: The gap in translational research that needs to be approached from both ends not only includes the appreciation of principal neural mechanisms (repair, sprouting, plasticity) and their assumed impact onto outcomes (even though humans and non primate animals may rely on slightly different supraspinal control for some movements), but also includes an understanding of the spatial (location and size of lesion) and temporal (timelines of damage and recovery) factors in spinal cord damage that can vary considerably between the different species being studied. Conclusion:The preclinical-clinical dialogue should be encouraged as a venue to improve the appreciation of discoveries in basic research, and to power valid discoveries towards a meaningful translation into advanced treatments downstream. Similarly, the upstream identification of appropriate clinical targets that take into account clinical constraints depends on reliable and advanced clinical information being provided to preclinical investigators.

Olfactory Ensheathing Cell Transplantation in Experimental Spinal Cord Injury: Effect size and Reporting Bias of 62 Experimental Treatments: A Systematic Review and Meta-Analysis

“…Omission of negative data renders an objective prioritization of experimental interventions for translation toward clinical trials difficult. The fragile and resource-intense translational path depends on objective measures, and its efficiency will be dependent on a bi-directional dialogue [ 23 ]. Meta-analyses based on systematic reviews contribute to this dialogue, as they are able to monitor for missing data and inflated effect sizes [ 24 – 26 ].…”

Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture

“…Refinements of impairment and activities measures as well as the establishment of Minimal Clinically Important Difference criteria for these SCI outcomes remain a challenge for the field. 45 When to measure the primary end point is also critical: demonstration of short-term (for example, 8-12 week) efficacy and safety will not prove that the benefit will last, especially when testing a treatment during the first year after injury. Key outcome examiners should be trained and be tested for inter-rater reliability.…”

Human neural stem cells in chronic spinal cord injury

“…Clinical experience teaches that the human spinal cord has a huge capacity for plasticity as for example witnessed by MRI studies in patients with enormous deformations of the cord (like compression, benign tumour formation or syringomyelia, albeit with no or only subtle neurological deficits). In these instances the cord can show extensive changes in morphology, which however require a very slow progression of the underlying disorder [13]. The later aspect might be of importance specifically in patients with severe and rather large areas of spinal cord damage where prolonged treatment might be essential to fully exploit the effects of regeneration and plasticity.…”