Biomarkers for Equine Athletes
If you spend any time keeping up on the latest research, even in general press articles, you’ll eventually come across mention of a “biomarker.” At its most basic definition, a biomarker is an indicator of biological activity or occurrence. The Food and Drug Administration further defines a biomarker as a “characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions.” In other words, a biomarker is something that is produced by the body which may be measured at higher or lower levels during health or disease. While many people may think biomarkers are only detected in the blood, it is important to point out that they can also be measured using radiography, microscopy, or with physiologic monitoring (like heart rate or blood pressure).
Within the context of horses, a recent cursory Google Scholar search for “equine” and “biomarker” retrieved more than 19,000 entries, which is not surprising given the broad definition of a biomarker. The addition of “injury” to the search criteria decreased the number of entries to approximately 10,000. This confirms that there is an ever-evolving push to understand and decrease injuries and lameness in horses using biomarkers. Nowhere is this more apparent than with equine athletes, where the drive to improve both welfare and performance go hand in hand. Research in this field involves looking at currently available and validated tests, as well as the identification of new biomarkers and tests to detect them.
Work from Cornell University, where researchers have a strong interest in liver enzymes and function, has suggested that gamma-glutamyl transferase (GGT) is elevated in racehorses with maladaptation to training and poor performance. While it is not yet known whether the elevated enzyme concentrations are the cause of poor performance, use of GGT as a biomarker could become more mainstream since testing is readily available at most veterinary labs. Another simple and readily available test is serum amyloid A (SAA), a sensitive marker of inflammation, which is often used to diagnose and monitor horses with infectious processes, such as bacterial infections. While research has shown SAA isn’t useful for detection of orthopedic (bone) injuries, there is potential that it may be useful for detection of some soft-tissue injuries.
One of the major focuses of equine musculoskeletal research is detecting injuries in racehorses before they occur. Most racehorses that sustain fractures during training or racing have preexisting bone or soft tissue damage. This tissue damage should lead to inflammation and the release of proteins or other biomarkers. Additional research has looked at the quantification of multiple proteins, which are thought to be joint or bone-specific, to predict injuries in racehorses. While this work has shown limited success in the U.S. and internationally, it has only been based on relatively small populations of injured horses. The limited number of horses makes it difficult to predict how well these results will hold up within the racing population as a whole.
Another exciting development with biomarkers and racehorse injuries comes from our lab at the University of Kentucky Gluck Equine Research Center, where we have been using messenger RNA (mRNA) to monitor a variety of different aspects of racing, including the occurrence of catastrophic racing injuries. With mRNA, we are able to identify approximately 75% of horses that are at risk for fracture using three different markers. Taken together, changes in these three markers (IGF-1, MMP-2, and IL-1RA) suggests that horses with catastrophic injuries have underlying inflammation. However, the level of inflammation may be so low that it is difficult to directly measure using currently available technologies, a limitation that isn’t applicable to mRNA analysis. We recently began a large-scale study to validate this research and expect to have results in late 2023. Ultimately, we believe that mRNA biomarkers have the potential to provide an economic and effective tool to the racing industry that can be used to identify horses at risk for fracture. In the future, we also hope to expand this work into other equine athletic disciplines for use as a monitoring and/or training tool.
Editor’s note: This is an excerpt from Equine Disease Quarterly, Vol. 31, No. 3, funded by underwriters at Lloyd’s, London, brokers, and their Kentucky agents. It was written by Allen Page, DVM, PhD.
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