As the quest continues for a better way to identify racehorses at risk for fatal injury, a study from the University of Kentucky's Gluck Equine Research Center may provide scientists and veterinarians a roadmap of where to look. At a regularly scheduled meeting Oct. 22, the Kentucky Horse Racing Commission received initial results from a study by Gluck researchers Dr. Allen Page and David Horohov looking at inflammatory biomarkers. Biomarkers are proteins, which can be produced at different levels in the body depending on changes and normal processes like inflammation.
Researchers have looked at biomarkers before to try finding some that would signal inflammation that may still be subclinical, or not producing recognizable symptoms yet in the horse. Previous efforts have yielded mixed results, in part because the body undergoes some amount of normal inflammation in response to exercise even when the horse isn't battling an underlying injury. Other biomarkers don't show up until the injury occurs, which makes them useless from a predictive standpoint.
Thanks to funding provided by the Kentucky Equine Drug Research Council (KEDRC), Page and Horohov are in the midst of a two-phase research project — the first looking at a new set of biomarkers and the second looking at messenger RNA, which signals the production of proteins like biomarkers. The second phase is still in progress, and Tuesday's meeting focused on the results from the first phase.
Page and Horohov gathered data from racetracks in four racing jurisdictions, testing blood taken pre-race for TCO2 testing and comparing results between horses who suffered fatal musculoskeletal injuries and competitors from the same races who did not. They examined 21 markers and found three — IGF-1, MMP-2, and IL1RN — which were present in different levels in injured horses versus non-injured horses.
These results made sense to the researchers. IGF-1 is known to play a role in bone development and repair, and it was increased in injured horses, suggesting chronic inflammation was present. Matrix metalloproteinase-2, or MMP-2, is thought to assist with tissue repair and fracture remodeling and was also elevated in injured horses. Interestingly, IL1RN is more commonly known as IRAP–a anti-inflammatory material derived from a horse's own blood and given therapeutically by veterinarians to reduce inflammation and aid in healing an injured horse. IRAP was decreased in fatally injured horses, suggesting the body's natural anti-inflammatory process had been disrupted for some reason. Horses with higher levels of IRAP were actually seven times less likely to suffer fatal injuries.
While those results are encouraging, Page cautioned that it will still be challenging to practically apply the new information. The three biomarkers weren't perfect predictors of impending injury; 24 percent of the time, a horse would not appear to be at risk based on its biomarker levels when in fact it did suffer a fatal injury and 12 percent of the time, tests suggested the horse was at risk of a fatal injury but the horse finished the race without a catastrophic breakdown.
Overall, the three biomarkers provided about 88 percent accuracy at identifying horses at risk.
The test is also expensive and in a research setting the tests took around 48 hours to complete. Page pointed out that those estimates are based on his team's study, where samples had to be tested for 21 different biomarkers. Reducing the number of markers tested would shorten that time, but it would still likely take 24 hours to get results.
Then there's the question of what to do with horses whose blood indicates they may be at risk. It remains unclear whether the commission legally can or should mandate imaging, particularly if the horse doesn't appear lame and no one is sure where the problem might be. Then there's the question of false positive tests — if a horse's entry was contingent upon a biomarker test, horses could be pulled from races who weren't actually at elevated risk, and it would be hard to know which were which.
Commission members acknowledged it will be a challenge to determine how biomarker data could be practically applied to a time sensitive screening process.
Page said he's hopeful the second phase of the study, which looks “upstream” at mRNA responsible for the production of proteins like biomarkers, may provide more specific guidance.
See Page's presentation here:
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