Systemic administration of epothilone B promotes axon regeneration after spinal cord injury

Jörg Ruschel, Farida Hellal, Kevin C. Flynn, Sebastian Dupraz, David A. Elliott, Andrea Tedeschi, Margaret Bates, Christopher Sliwinski, Gary Brook, Kristina Dobrindt, Michael Peitz, Oliver Brüstle, Michael D Norenberg, Armin Blesch, Norbert Weidner, Mary B Bunge, John Bixby, Frank Bradke

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197 Scopus citations

Abstract

After central nervous system (CNS) injury, inhibitory factors in the lesion scar and poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier-permeable microtubule-stabilizing drug, epothilone B (epoB), decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug-elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury.

Original languageEnglish (US)
Pages (from-to)347-352
Number of pages6
JournalScience
Volume348
Issue number6232
DOIs
StatePublished - Apr 17 2015

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Cite this

Ruschel, J., Hellal, F., Flynn, K. C., Dupraz, S., Elliott, D. A., Tedeschi, A., Bates, M., Sliwinski, C., Brook, G., Dobrindt, K., Peitz, M., Brüstle, O., Norenberg, M. D., Blesch, A., Weidner, N., Bunge, M. B., Bixby, J., & Bradke, F. (2015). Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science, 348(6232), 347-352. https://doi.org/10.1126/science.aaa2958