Phase II Double-blinded Randomized Controlled Clinical Trial of Chondroitinase ABC by Intraspinal Injection for Treatment of Severe Chronic Spinal Cord Injury in 60 Pet Dogs

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dc.contributor.advisor Nick Jeffery
dc.contributor.author Hu, Hilary
dc.contributor.department Biomedical Sciences
dc.date 2018-08-11T17:24:09.000
dc.date.accessioned 2020-06-30T03:07:31Z
dc.date.available 2020-06-30T03:07:31Z
dc.date.copyright Fri Jan 01 00:00:00 UTC 2016
dc.date.embargo 2001-01-01
dc.date.issued 2016-01-01
dc.description.abstract <p>Traumatic spinal cord injury is a devastating neurologic condition in both veterinary and human medicine and despite research yielding numerous potential interventions with remarkable efficacy demonstrated in rodent models, none has advanced to successful clinical translation. Pet dogs’ predilection for sustaining spinal cord injury, typically due to intervertebral disc herniation or vertebral column fracture, makes them a suitable clinical model in which putative interventions for spinal cord injury can be tested. In recent years, there has been a growing body of experimental evidence that attests to the efficacy of chondroitinase ABC in promoting axonal regeneration and functional recovery after spinal cord injury by reactivating neuroplasticity. Chondroitinase ABC is a commercialized bacterial enzyme that selectively deglycosylates chondroitin sulfate proteoglycans and thereby disrupts the perineuronal nets that limits axonal regeneration. In this 60-dog clinical trial, we examined the therapeutic effect of chondroitinase ABC on the primary outcome measure, pelvic-thoracic limb gait coordination, and several secondary parameters, including motor- and sensory-evoked potentials and urinary bladder compliance. While our study failed to detect a therapeutic effect in chronic, severe thoracolumbar spinal-injured dogs, it has established drug safety in a clinical large animal model. Thus, this study has provided a platform for future investigations in which the dose, route and timing of chondroitinase ABC administration, as well as patient selection, can be adjusted to maximize its potential therapeutic effect and benefit spinal-injured human and veterinary patients, especially if a more treatment-responsive subgroup could be identified.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/etd/15935/
dc.identifier.articleid 6942
dc.identifier.contextkey 11169350
dc.identifier.doi https://doi.org/10.31274/etd-180810-5562
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath etd/15935
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/30118
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/etd/15935/Hu_iastate_0097E_15495.pdf|||Fri Jan 14 20:48:53 UTC 2022
dc.subject.disciplines Medicine and Health Sciences
dc.subject.disciplines Veterinary Medicine
dc.subject.keywords Chondroitinase
dc.subject.keywords Clinical trial
dc.subject.keywords Paralyzed dog
dc.subject.keywords Regeneration
dc.subject.keywords Spinal cord injury
dc.title Phase II Double-blinded Randomized Controlled Clinical Trial of Chondroitinase ABC by Intraspinal Injection for Treatment of Severe Chronic Spinal Cord Injury in 60 Pet Dogs
dc.type article
dc.type.genre dissertation
dspace.entity.type Publication
relation.isOrgUnitOfPublication 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9
thesis.degree.discipline Neuroscience
thesis.degree.level dissertation
thesis.degree.name Doctor of Philosophy
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