Peer-reviewed veterinary case report
Metalloproteinase inhibitor improves recovery in dogs with spinal
By Levine, Jonathan M et al.·Published in PloS one·2014·Department of Small Animal Clinical Sciences, United States·View original on PubMed →
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Original publication title: Efficacy of a metalloproteinase inhibitor in spinal cord injured dogs.
- Species:
- dog
Plain-English summary
A group of dogs with spinal cord injuries received either a new treatment called GM6001 or a control solution to see if it would help improve their recovery. The study found that while GM6001 reduced certain harmful proteins in the blood, the dogs that showed better recovery were actually those given the control solution, dimethyl sulfoxide. In severely injured dogs, those treated with the control had better motor scores compared to those who received saline. Overall, the results suggest that the control treatment may have contributed more to recovery than GM6001 itself.
People also search for: dog spinal cord injury treatment · GM6001 for dogs · dimethyl sulfoxide for dog recovery · dog motor function after injury
Abstract
Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic events that emerge in the acutely injured cord.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/24788791/