Efficacy of a Metalloproteinase Inhibitor in Spinal Cord Injured Dogs

PLoS ONE, 2014 · DOI: 10.1371/journal.pone.0096408 · Published: May 1, 2014

Spinal Cord Injury Neurology Veterinary Medicine

Simple Explanation

This research investigates a drug called GM6001 for treating spinal cord injuries in dogs. GM6001 blocks certain enzymes that can worsen the damage after an injury. The study found that while GM6001 did reduce the activity of these enzymes, it was actually a different substance, DMSO, that seemed to help dogs with severe injuries recover better. DMSO has potential to protect nerves, and this study suggests it could be a useful part of treatment for spinal cord injuries.

Study Duration

September 2008 and February 2012

Participants

Client-owned dogs with IVDH-associated SCI (n = 107)

Evidence Level

Level 2: Randomized, blinded, placebo-controlled trial

Key Findings

1
GM6001 reduced serum protease activity in spinal cord injured dogs compared to the other two groups.
2
In dogs with severe spinal cord injuries, those treated with saline had a significantly lower mean motor score compared to dogs receiving dimethyl sulfoxide or GM6001.
3
Improved neurological outcomes are attributed to dimethyl sulfoxide, which may target diverse secondary pathogenic events in the acutely injured cord.

Research Summary

The study evaluated the effectiveness of GM6001, a metalloproteinase inhibitor, in dogs with naturally occurring spinal cord injuries. The drug's safety and how it moves through the body were tested. The clinical trial involved three groups of dogs with spinal cord injuries: one treated with GM6001 in DMSO, one with DMSO alone, and one with saline. The primary outcome was the Texas Spinal Cord Injury Score (TSCIS) at 42 days post-injury. Dogs with severe spinal cord injuries treated with either GM6001 in DMSO or DMSO alone showed significantly better functional recovery compared to those treated with saline, suggesting DMSO's role in improving neurological outcomes.

Practical Implications

DMSO as a potential treatment

DMSO, commonly used as a solvent, may have neuroprotective properties and could be repurposed for combinatorial therapies for SCI.

Extended therapeutic window

DMSO's therapeutic window may extend up to 48 hours post-injury, potentially benefiting a broader range of spinal cord injury patients.

Need for rigorous evaluation of DMSO

Given conflicting reports about the efficacy of DMSO, there is a need to rigorously evaluate its safety, dosing, and efficacy, particularly in synergistic combinations.

Study Limitations

1
Species differences in responsiveness to GM6001 and/or MMP-directed pathogenesis.
2
The timing between SCI and administration of GM6001 may not have been optimal.
3
The use of dogs with thoracic and lumbar spinal cord lesions could have influenced the ability to detect drug-related effects.

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