Spinal cord injury: plasticity, regeneration and the challenge of translational drug development

• Published in: Trends in neurosciences (Regular ed.) Vol. 32; no. 1; pp. 41 - 47
• Main Authors: Blesch, Armin, Tuszynski, Mark H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.01.2009; Elsevier; Elsevier Sequoia S.A
• Subjects: Animals; Biological and medical sciences; Clinical trials; Clinical Trials as Topic; Disease Models, Animal; Diseases of the osteoarticular system; Diseases of the spine; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Humans; Medical sciences; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Nervous system; Neurology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurosciences; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Tissue engineering; Vertebrates: nervous system and sense organs; Ability; Human; Animal model; Nervous system diseases; Variability; Central nervous system; Contusion; Review; Complexity; Regeneration; Functional recovery; Spinal cord trauma; Central nervous system disease; Plasticity; Clinical trial; Strategy; Spinal cord disease
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2008.09.008

Over the past three decades, multiple mechanisms limiting central nervous system regeneration have been identified. Here, we address plasticity arising from spared systems as a particularly important and often unrecognized mechanism that potentially contributes to functional recovery in studies of ‘regeneration’ after spinal cord injury. We then discuss complexities involved in translating findings from animal models to human clinical trials in spinal cord injury; current strategies might be too limited in scope to yield detectable benefits in the complex and variable arena of human injury. Our animal models are imperfect, and the very variability that we attempt to control in the course of conducting rigorous research might, ironically, limit our ability to identify the most promising therapies in the human arena. Therapeutic candidates are most likely to have a detectable effect in human trials if they elicit benefits in severe contusion and larger animal models and pass the test of independent replication.