The Horse as a Model for Human Research
Compared to mice or rats, horses might not inherently seem like great models for studying human physiology and disease. They are large, expensive to house and feed, and their bites (and kicks!) could cause a wee bit more damage than their rodent counterparts'. But horses' size, athleticism, aging processes, and spectrum of natural diseases actually make them perfect for the role.
"The horse serves as an excellent model for studying human diseases, especially for studying metabolic disorders such as obesity," says Nicholas Frank, DVM, PhD, Dipl. ACVIM, professor and department chair of clinical sciences at Tufts University's Cummings School of Veterinary Medicine.
Horses' and humans' basic body systems and physiology are quite similar, so in many cases research conducted in one species could be translated to the other. Frank notes that the list of diseases and medical conditions horses and humans have in common is rather extensive. Some examples include uveitis (inflammation of the cellular layer of the eye), cancer (e.g., melanoma), and respiratory diseases (asthma in humans, for example, resembles inflammatory airway disease in horses).
However, this does not mean horses are being used as proverbial guinea pigs. Instead, using horses as models for studying human disease more accurately falls under the canopy of "One Health," which is an international movement led by doctors and veterinarians that considers "one medicine for all." Its mission is to "promote, improve, and defend the health and well-being of all species by enhancing cooperation and collaboration between physicians, veterinarians, other scientific health and environmental professionals and by promoting strengths in leadership and management to achieve these goals," according to www.onehealthinitiative.com.
The One Health approach to medicine was first described in the late 1800s, but it has only recently gained momentum. Now, the concept that all animals, including horses and humans as well as the environment, are "in it together" is becoming increasingly recognized and embraced by medical and veterinary professionals and organizations such as the American Medical Association, the American Veterinary Medical Association, the American Society of Tropical Medicine and Hygiene, the Centers for Disease Control and Prevention, the USDA, and the U.S. National Environmental Health Association.
How Horses Can Help
Among these parallels are a few standouts: According to Frank, horses and humans have unique similarities in their insulin resistance response to overfeeding. The horse therefore provides an excellent model of obesity for both children and adults. Human researchers can glean from data published in veterinary studies on treating insulin resistance in horses, and vice versa. In addition, researchers can use their study results involving older horses to help investigate human geriatric conditions because, unlike rats, rodents, and other research animals, the horse's life span can exceed 30 years.
"Recent research has revealed that the immune function decreases in old horses, as it does in older people," relays Frank. "On the other end of the spectrum, foals can also be studied (retrospectively, which involves examining case re-ports) to investigate diseases of infants and children. It is already known that hormonal imbalances in sick foals follow the same patterns as human babies."
Research into naturally occurring diseases in the horse such as osteoarthritis and cancer can also benefit human health. Stem cell research for musculoskeletal disorders (i.e., arthritis and tendon injuries) is an excellent example of how veterinary medicine is plowing the path for regenerative therapy use in human medicine. Below, we'll discuss some of the important medical conditions shared by humans and horses and relay the most up-to-date information available.
Equine metabolic syndrome (EMS) is the term used to describe horses with abnormal fat distribution and insulin resistance. The latter is a condition in which increased insulin production is required to maintain (or attempt to maintain) circulating blood sugar levels within normal limits. Human patients with metabolic syndrome exhibit similar clinical signs to horses with EMS and are at risk for developing various diseases, such as diabetes mellitus and stroke. On the other hand, horses with metabolic syndrome don't develop diabetes, but instead are at risk for developing acute or (more commonly) chronic laminitis.
"Horses are of interest to researchers studying metabolic syndrome in humans because they remain in a state of compensated insulin resistance for years without developing diabetes," says Frank. "Improving our understanding of insulin resistance in horses might, therefore, lead to the development of new treatments for metabolic syndrome in humans." Simply put, horses are ideal models for studying the "prediabetes phase" for a long time in a single animal.
Other researchers have noted that equine and human metabolic syndrome might also share underlying evolutionary and environmental components.
"Humans are plagued with chronic diseases such as obesity, metabolic syndrome, and type 2 diabetes," says Molly McCue, DVM, MS, PhD, Dipl. ACVIM, assistant professor at the University of Minnesota's College of Veterinary Medicine. Many of these chronic diseases are thought to result from genetic predisposition and the modern human environment. "Horses and humans are quite similar in how they evolved and how their lives and husbandry have changed over the past 100 years. As a result, horses and humans share a number of chronic diseases."
McCue is a proponent of One Health and is supported by a K08 award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (part of the National Institutes of Health), a grant designed to facilitate research that might benefit animals and humans alike.
"The domestic horse has been bred for such traits as endurance, strength, speed, and efficient conversion of feedstuff to fuel," says McCue. "Nowadays, these metabolically efficient horses that we have bred are housed in small stalls or pad-docks, have limited physical activity, and yet are fed high-calorie feedstuffs. In today's environment metabolic efficiency may put these horses at risk for developing obesity, insulin resistance, and equine metabolic syndrome."
McCue's EMS research aims to identify the genes underlying disease development and the interaction between those genes and the modern horse's environment. "We hope that insight into the genetic predisposition in the horse will lead to greater understanding of the genes and gene pathways that may also be involved in human metabolic syndrome," she says. Ultimately, this improved understanding of the genes involved in EMS might also help breeders avoid perpetuating EMS in horses.
There's another reason McCue is taking a close look at the role of genes: The Horse Genome Project that was completed in 2009, in which an international team of scientists built preliminary maps of the horse genome and began using genomics tools to address health issues in horses, was an amazing feat. But equally exciting was researchers' discovery that the equine genome is very similar to that of humans.
"Horses and humans suffer from similar illnesses, so identifying the genetic culprits in horses promises to deepen our knowledge of disease in both organisms," said senior author Kerstin Lindblad-Toh, PhD, scientific director of vertebrate genome biology at the Broad Institute of MIT and Harvard and a professor of comparative genomics at Uppsala University in Sweden, in a press release issued from the Broad Institute in November 2009. "The horse genome sequence is a key enabling resource toward this goal."
To date, scientists have noted that 90 hereditary diseases in horses have similarities to those in humans. Thus, continued research on these equine genetic diseases (e.g., severe combined immunodeficiency in Arabian horses, and polysaccharide storage myopathy--or PSSM--which involves the mutation of the GYS1 gene) could benefit both species.
"PSSM is a debilitating and potentially life-threatening glycogen storage disease characterized by muscle pain, muscle wasting, lameness and gait abnormalities, and more," explains McCue. In 2008 she reported in an article published in Genomics the discovery of a mutation in GYS1, a gene that encodes the synthesis of a skeletal muscle enzyme called glycogen synthase. This enzyme is responsible for converting glucose into glycogen (a storage form of glucose). Horses with a specific mutation in the GYS1 gene produce more enzyme than they need and, therefore, have excess glycogen in their skeletal muscle. Affected horses are diagnosed with PSSM.
This unique genetic mutation of the glycogen synthase enzyme is a "gain-of-function" mutation rather than the more common type of genetic mutation, which results in loss of function.
The discovery of the GYS1 mutation underlying PSSM is the first description of a gain-of-function mutation (meaning the enzyme is overactive) in this gene causing disease in any species. Identifying this disease mechanism in the horse has created a new direction for investigating unknown causes of illness in other species, including humans. Approximately 50% of glycogen storage diseases described in human patients have an unknown cause.
Horses and humans also sustain similar muskuloskeletal injuries. Joint disease (due to trauma, for example) and tendon injuries are common in both species and can develop into career-limiting conditions. Currently, no cure for osteoarthritis in humans or horses exists, and tendon injuries are notorious for requiring prolonged layups and having a propensity to recur.
Regenerative medicine for the treatment of musculoskeletal disorders such as tendon injuries and osteoarthritis is advancing in leaps and bounds in the veterinary industry, but it is still shrouded in red tape in the human world. This is because FDA approval is not required for veterinarians to use stem cells and platelets in horses, as it is for human medicine. Therefore, research on these treatment modalities in horses is progressing quickly, and a number of regenerative therapies are already commercially available for horses.
Stem cells, derived from either adipose (fat) tissue or bone marrow, and platelet-rich plasma are the two most common regenerative therapies in equine medicine. Although these therapies are commercially available, more research is needed to delineate the exact procedure (how many cells to extract, when to inject them, and how often to inject them), and more studies using clinical cases are needed to better establish treatment outcome. For example, what exactly are the chances that a horse with a bowed tendon will return to athletic soundness after treatment? As researchers answer these types of questions in horses, they are paving the way for similar treatments in humans.
Equine veterinarians and veterinary researchers play an important role in One Health. Their cooperation with each other and other medical professionals has and will continue to benefit both veterinary and human medicine in countless ways. As Bob Marley said it best: "One Love, One Heart. Let's get together and feel all right."
About the Author
Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.
POLL: University Equine Hospitals