Biology Reference
In-Depth Information
CHAPTER SEVEN
From Bench to Beside to Cure
Spinal Cord Injury: Lost in
Translation?
Andreas Hug, Norbert Weidner
1
Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany
1
Corresponding author: e-mail address: norbert.weidner@med.uni-heidelberg.de
Contents
1.
Introduction
174
1.1 Stimulated macrophages
178
1.2 Embryonic stem cells
180
1.3 Anti-Nogo-A
182
1.4 RhoA inactivation (C3 transferase, Cethrin; see Volume 105,
Chapter 6
for
more details)
183
1.5 Requirements for appropriate preclinical data acquisition
186
2. Conclusion
191
References
192
Abstract
Despite intense efforts to overcome the inhospitable milieu for axonal regeneration
within the damaged spinal cord an evidence-based repair strategy promoting relevant
functional improvement is still not available for spinal cord injured individuals. Never-
theless, several preclinical axonal regenerative strategies were developed all the way to
phase I/II clinical trials, which have recently been terminated. The aim of this chapter is
to critically review translated preclinical treatment strategies with respect to their con-
formity with previously published guidelines and requirements for preclinical studies
leading to clinical trials in human subjects with spinal cord injury (SCI). Cell-based strat-
egies (macrophage and embryonic stem cell grafting) and the administration of C3
transferase inhibitors and anti-Nogo-A antibodies were investigated. Overall, these four
approaches comply with preclinical quality standards to varying degree. For future pre-
clinical analyses, several additive components such as defined criteria for robustness of
observed effects, a clear confirmation of underlying structural mechanisms, and the
implementation of appropriate preclinical rehab approaches should be considered in
order to increase the quality and consequently the likelihood of respective therapeutic
strategies to succeed in human individuals suffering from SCI.
