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Thread: Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine SCI

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    Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine SCI

    Brain. 2018 Feb 9.


    Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury.


    Hu HZ1, Granger N2, Pai SB3, Bellamkonda RV4, Jeffery ND1.

    Author information

    Abstract
    Many hundreds of thousands of people around the world are living with the long-term consequences of spinal cord injury and they need effective new therapies. Laboratory research in experimental animals has identified a large number of potentially translatable interventions but transition to the clinic is not straightforward. Further evidence of efficacy in more clinically-relevant lesions is required to gain sufficient confidence to commence human clinical trials. Of the many therapeutic candidates currently available, intraspinally applied chondroitinase ABC has particularly well documented efficacy in experimental animals. In this study we measured the effects of this intervention in a double-blinded randomized controlled trial in a cohort of dogs with naturally-occurring severe chronic spinal cord injuries that model the condition in humans. First, we collected baseline data on a series of outcomes: forelimb-hindlimb coordination (the prespecified primary outcome measure), skin sensitivity along the back, somatosensory evoked and transcranial magnetic motor evoked potentials and cystometry in 60 dogs with thoracolumbar lesions. Dogs were then randomized 1:1 to receive intraspinal injections of heat-stabilized, lipid microtube-embedded chondroitinase ABC or sham injections consisting of needle puncture of the skin. Outcome data were measured at 1, 3 and 6 months after intervention; skin sensitivity was also measured 24 h after injection (or sham). Forelimb-hindlimb coordination was affected by neither time nor chondroitinase treatment alone but there was a significant interaction between these variables such that coordination between forelimb and hindlimb stepping improved during the 6-month follow-up period in the chondroitinase-treated animals by a mean of 23%, but did not change in controls. Three dogs (10%) in the chondroitinase group also recovered the ability to ambulate without assistance. Sensitivity of the dorsal skin increased at 24 h after intervention in both groups but subsequently decreased to normal levels. Cystometry identified a non-significant improvement of bladder compliance at 1 month in the chondroitinase-injected dogs but this did not persist. There were no overall differences between groups in detection of sensory evoked potentials. Our results strongly support a beneficial effect of intraspinal injection of chondroitinase ABC on spinal cord function in this highly clinically-relevant model of chronic severe spinal cord injury. There was no evidence of long-term adverse effects associated with this intervention. We therefore conclude that this study provides strong evidence in support of initiation of clinical trials of chondroitinase ABC in humans with chronic spinal cord injury.

    KEYWORDS:
    adverse effects; chondroitin sulfate proteoglycan; dog; glial scar; translation

    https://www.ncbi.nlm.nih.gov/pubmed/29444239
    “As the cast of villains in SCI is vast and collaborative, so too must be the chorus of hero's that rise to meet them” Ramer et al 2005

  2. #2
    Senior Member lynnifer's Avatar
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    Well, isn't this what a lot of us were waiting for? Not sure it's that impressive.
    Roses are red. Tacos are enjoyable. Don't blame immigrants, because you're unemployable.

    T-11 Flaccid Paraplegic due to TM July 1985 @ age 12

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    meh. bummer.
    T3 complete since Sept 2015.

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