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@ARTICLE{Ruschel:140031,
author = {Ruschel, Jörg and Bradke, Frank},
title = {{S}ystemic administration of epothilone {D} improves
functional recovery of walking after rat spinal cord
contusion injury.},
journal = {Experimental neurology},
volume = {306},
issn = {0014-4886},
address = {Orlando, Fla.},
publisher = {Academic Press},
reportid = {DZNE-2020-06353},
pages = {243-249},
year = {2018},
abstract = {Central nervous system (CNS) injuries cause permanent
impairments of sensorimotor functions as mature neurons fail
to regenerate their severed axons. The poor intrinsic growth
capacity of adult CNS neurons and the formation of an
inhibitory lesion scar are key impediments to axon
regeneration. Systemic administration of the microtubule
stabilizing agent epothilone B promotes axon regeneration
and recovery of motor function by activating the intrinsic
axonal growth machinery and by reducing the inhibitory
fibrotic lesion scar. Thus, epothilones hold clinical
promise as potential therapeutics for spinal cord injury.
Here we tested the efficacy of epothilone D, an epothilone B
analog with a superior safety profile. By using liquid
chromatography and mass spectrometry (LC/MS), we found
adequate CNS penetration and distribution of epothilone D
after systemic administration, confirming the suitability of
the drug for non-invasive CNS treatment. Systemic
administration of epothilone D reduced inhibitory fibrotic
scarring, promoted regrowth of injured raphespinal fibers
and improved walking function after mid-thoracic spinal cord
contusion injury in adult rats. These results confirm that
systemic administration of epothilones is a valuable
therapeutic strategy for CNS regeneration and repair after
injury and provides a further advance for potential clinical
translation.},
cin = {AG Bradke},
ddc = {610},
cid = {I:(DE-2719)1013002},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29223322},
doi = {10.1016/j.expneurol.2017.12.001},
url = {https://pub.dzne.de/record/140031},
}