Investigating Metabolic Stress and Viral Hepatitis in the Pathogenesis of Maladaptation to Training Syndrome in Thoroughbred Horses: A Nested Case-Control Study

Principal Investigator: Sabine Mann

Co-PI: Thomas J. Divers

Department of Population Medicine and Diagnostic Sciences
Sponsor: Grayson-Jockey Club
Title: Investigating Metabolic Stress and Viral Hepatitis in the Pathogenesis of Maladaptation to Training Syndrome in Thoroughbred Horses: A Nested Case-Control Study
Project Amount: $41,392
Project Period: April 2019 to March 2020

DESCRIPTION (provided by applicant): 

 Maladaption to training syndrome is characterized by the increase in a specific enzyme, y-Glutamyl-Transferase (GGT), in the blood of racing Thoroughbreds. It is currently unknown what causes the abnormally high enzyme and if it is the cause of the poor performance of affected horses. We seek to shed light to the possible causes and will test different potential factors that may help us explain this syndrome in this study so that we can help prevent or treat the affected horses. The first factor could be a metabolic problem that causes horses to have high GGT activity and makes them less able to respond to the challenge of a race. This may be due to the fact that strenuous exercise can lead to detrimental accumulation of the byproducts of burning fuel, so called free radicals, or oxidative stress. We will follow horses over time, beginning during the lower-intensity early training season, so that we can identify changes early and before abnormal enzyme levels develop. This way we will be able to show if changes in metabolic pathways develop before GGT activity increases.
   The second factor is a possible infection with a recently discovered virus that targets the liver and causes an inflammation of the organ, called hepatitis. Such an infection could explain why GGT increases as it has a high concentration in the liver. We could show previously that approximately 18 % of horses racing in California had high GGT concentrations. Of those horses, 3-5% were infected with one of the two equine viruses, hepacivirus and parvovirus, respectively. Although the number of horses that were found to be infected is low, the risk to have high GGT concentrations was higher in infected horses, and thus it could be a contributing factor to high GGT activity. Therefore, we think it is important to determine if liver infection with viruses could be causing the maladaptation to training syndrome.
   Both questions will be answered by a study of a group of healthy Thoroughbred horses that will be blood samples over time. This will allow us to detect early on when the GGT concentration is increasing and study the changes in metabolism or viral infection that happen concurrently or before GGT increases. To do this, we will quantify over 250 different metabolites in the serum samples of healthy and high GGT horses (15 animals each), and compare the findings to find metabolic clues to understand the syndrome. We will also subject these horses to a training race to see if some of the metabolic markers that we are looking for may only be changing for a short period of time after the animals are challenged. In addition, we will detect and quantify virus particles in the blood of these horses to determine if recent virus infection is more likely in horses that develop high GGT concentrations. Our goal is to find the reason for the increase in GGT activity so that we can help identify possible strategies to prevent and treat horses that develop this syndrome.