Studies at UF Veterinary College Aim to Advance Horse Health

If you have visited the Ocala area recently, you would have to agree that Florida's horse business is growing by leaps and bounds. The World Equestrian Center, a 378-acre state-of-the-art equine competition venue in its second year of operation, is partially responsible for the influx of horses to the area. Next month, the University of Florida–the state's only vet school–is scheduled to open a world-class hospital located at WEC, offering advanced diagnostics and treatment for equine competitors and companion animals. The hospital will be open to all horses, not just those competing at the center.

Just 25 miles north of the WEC, UF's College of Veterinary Medicine, located in Gainesville, Florida, ranks number nine among veterinary medical colleges according to the U.S. News & World Report. Researchers at the Large Animal Hospital tackle everything from equine allergies to the complex questions of performance-enhancing drugs for equine athletes, and operate programs in the field to teach backyard livestock owners the importance of regular vaccines and dewormers. The Large Animal Hospital provides diagnostics and care to horses, cattle, goats, alpacas, llamas, and other large farm or food animals and serves the region with state-of-the-art emergency rescue vehicles and training in animal rescue during disasters for first-responders.

Defined in part by the world-class horse farms, nurseries, and all-encompassing horse business in Florida, the scope of equine-related topics facing researchers and veterinarians at UF is wide and the stakes are high. Florida is home to year-round Thoroughbred racing and one of America's richest Thoroughbred races, the $3-million GI Pegasus World Cup at Gulfstream Park, as well as two of the world's busiest and most established horse show venues in Wellington and Ocala. According to the Florida Department of Agriculture and Consumer Services, the horse industry in Florida generates an annual $6.8 billion economic impact on the GDP in the state.

A recent visit to the veterinary college uncovered three studies that are of particular relevance to the Thoroughbreds: a study by Dr. Rosanna Marsella to find an alternative to steroid treatment for allergies in horses, a study by Dr. Taralyn McCarrel in conjunction with the Florida Racing Lab on Liposomal BupiVacaine and its therapeutic benefits in racehorses, and a study by Dr. Sally DeNotta to find a non-opioid sedative for use in safely extracting a sample of Cerebrospinal fluid (CSF) outside the confines of an equine hospital.

When horses suffer from skin allergies or lung ailments caused by allergic reactions, the most prescribed treatment involves steroids often for an extended period of time. Dr. Rosanna Marsella said she was making progress in her attempt to find a biologic treatment for horses plagued by allergies. The use of novel biologic agents to treat allergies in horses would avoid the side effects, limitations, and detriments of long-term steroid use.

“Currently, allergies in the skin and lungs in horses are primarily treated with steroids,” said Marsella. “Steroids have a lot of potential for adverse effects. Horses, more than other species, are sensitive to these adverse effects and the results can be devastating. We know that biologics work in human medicine. We have one that works on the small animal side and my goal now is to develop one for horses.”

“A biologic is an antibody that targets specifically and directly the molecule causing the allergic response. It can be injected with minimal to no side effects because it is not a drug. The antibody removes that molecule from the system.”

“As a veterinarian, I see a lot of horses that are on steroids for a long period of time and it is unhealthy. Also, equine athletes cannot compete on steroids. There is therefore a tremendous need to develop a treatment that is effective, safe and sustainable that is not steroids.”

Regarding the progression of research in horses, Marsella, a horse owner herself, sees the science as less advanced for horses as it is for humans or small animals. The approach, as she sees it, has been largely a reactive one. Finding a biologic to treat allergies is a first step in the right direction towards sustainable treatments for horses. The next step for this study is the production of mono antibodies. The clinical trial phase will follow.

Dr. Taralyn McCarrel has been at UF since 2015. McCarrel is an orthopedic surgeon, teaches orthopedics, and does research on orthopedic needs and regenerative therapies. McCarrel also heads a program in collaboration with the Florida Racing Lab, responsible for the drug testing for racing in the state, to study pharmacokinetics or the way that drugs are distributed through the body and cleared from the body, as well as the therapeutic effects of some drugs on horses.

“Generally, we help the racing lab to establish their methodologies of how they do the testing and produce research that supports the levels they determine are acceptable,” said McCarrel.

“Dr. Cindy Cole [of Florida Racing Lab] and I will discuss drugs that we think are important to study either because they are new drugs or drugs that have a newly discovered effect–either as a therapeutic drug or in giving a competitive advantage.”

UF maintains a group of Thoroughbred racehorses that are kept in racing condition with a high-speed treadmill to provide subjects that are as close as possible to the population being tested at the tracks.

Drs. McCarrel and Cole collaborated on looking at a new formulation of a local anesthetic called Bupivacaine. Bupivacaine is often used for pain in post-operative settings and acts as a nerve-blocking anesthetic that lasts several hours. The new formulation called liposomal bupivacaine is long-acting and can provide relief for up to three days.

“Liposomal bupivacaine is meant to be a long-acting local anesthetic and we looked at it from two perspectives. One was to make sure that we could detect the drug to ensure that it could not be used to make a horse that is lame be comfortable in a race,” said McCarrel. “Another important piece was that the drug could be very useful. So, could we determine how long it lasts, and is there a way that the effects of the drug would be beneficial to the horse?”

McCarrel also completed a study on the effects of cannabidiol (CBD) treatments in horses (written results are expected soon) and they have a currently ongoing study on bisphosphonates which clear from circulation quickly, and then go to the bone where as of now, they cannot be detected without invasive techniques. The study aims to find out if bisphosphonates are released back into circulation in a detectable way as the bone remodels.

Dr. Sally DeNotta is a clinician in the large animal hospital and her specialty is in infectious disease and neurologic disease. Her research focuses on topics that affect equine practitioners who are out seeing horses in the field.

“We just completed a research study here at UF looking at alternative options to opioid medications in equine practice,” said DeNotta. “Opioids are very potent and effective analgesics in reducing pain throughout the body, including the brain and spinal cord. They are often used in combination with other medications to increase the level of sedation during potentially painful procedures.”

“Morphine is a potent opioid, and has traditionally been the analgesic of choice for collecting cerebrospinal fluid (CSF), an important diagnostic sample for horses with neurologic disease. Because morphine carries a high risk for illicit use, it is highly regulated by the DEA and is rarely carried on veterinarians' vehicles, thereby limiting their ability to perform this procedure outside of a veterinary hospital.”

“We sought to find out if there are opioid-free sedation protocols that practitioners can use to collect CSF from standing horses. This would allow them to perform this valuable diagnostic procedure while avoiding the regulatory liability and risk that comes with using controlled medications,” said DeNotta.

“The results of this study revealed non-opioid sedation protocols that worked just as well as morphine,” said DeNotta. “We found that a combination of detomidine and xylazine, two non-controlled sedatives used commonly in equine practice, allowed for equal procedural success and efficiency when compared to the morphine protocol. This research provides safe and effective sedation alternatives for practicing veterinarians, while also supporting recent initiatives to broadly reduce the use of opioids in both human and veterinary medicine.”

The three studies are a small sample of the wide array of topics being tackled at UF College of Veterinary Medicine. In the Thoroughbred business, where so many horses are retired from racing at a young age, it is critical to have dedicated researchers who help to create treatments that will prolong a horse's health, wellness, and soundness to extend their active life before it is time for a real retirement.

For more information about the UF College of Veterinary Medicine go to https://largeanimal.vethospitals.ufl.edu/ and to help support their work, contact Jacquie Basha at 954-881-0003.

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University Of Florida Vets Use Placenta-Derived Treatment For Animals With Severe Bone Loss

A human placenta-derived compound developed by a University of Florida faculty member in the Herbert Wertheim College of Engineering is being used with promising results by veterinarians at UF's College of Veterinary Medicine to treat animals with severe bone loss.

Without the compound, the animals — which included a giraffe at the Jacksonville Zoo and Gardens and two pet dogs — would have almost certainly faced amputation of the affected areas, the veterinarians said.

The product's developer, Peter McFetridge, Ph.D., the Integra Lifesciences Term Professor in the J. Crayton Pruitt Family Department of Biomedical Engineering, studies the engineering of viable “living” tissues and organs for the repair and regeneration of diseased tissues. Stan Kim, BVSc., an associate professor of small-animal surgery at UF, learned of McFetridge's work and was intrigued about the placental compound he had been testing in rodent models with some success.

McFetridge and Kim began discussing possibilities for the product's additional use in small animals. Kim treated the dogs with the new compound at UF's Small Animal Hospital earlier this year.

“Both dogs had very bad fractures that did not heal and had lost a lot of bone,” Kim said. “Typical treatments usually fail in these types of cases.”

The dogs were completely healed after the placental treatment, he said, and are doing very well.

“The most exciting thing about the placental compound is that it seems to regenerate bone in a remarkable manner,” Kim said. “Although our main excitement is with regenerating bone, we have also had very positive results with wounds.”

Meanwhile, Kim's colleague, Adam Biedrzycki, BVSc., Ph.D., an assistant professor of equine surgery at UF, had been contacted in January by the Jacksonville Zoo and Gardens about the possibility of helping with the treatment of a 2-year-old reticulated giraffe named JoJo, who had become severely lame in October. Despite various treatments provided at the zoo, JoJo's foot problems had worsened.

“They asked if I or a colleague had any interest in consulting or participating in the case,” Biedrzycki said.

JoJo had a severe case of septic arthritis in the medial claw of her right front foot, he said. The zoo had been treating the giraffe with analgesics, antibiotics and stall rest, and had even applied a custom-made boot from a farrier who works with exotic hoof stock. However, radiographs appeared to show bone abnormalities and deterioration, contributing to lesions and fluid drainage.

“I told them that giraffes are certainly not my area of expertise, but in a bovine or horse with this condition we would do massive bone grafts, place antibiotic beads, administer antibiotics directly into the limb and spend lots of time and money trying to save the digit. In a cow, we would drill out and remove the dead or damaged tissue surrounding the foot bone. Then we would cast it followed by regular bandage changes on the limb and leave it to heal.”

That was essentially what was done with the giraffe, he said — but with the addition of the placental compound.

Biedrzycki spoke with Kim, who had used the placental compound successfully in a few cases. Kim put Biedrzycki in touch with McFetridge to further discuss the product and its potential for treating infections and stimulating bone growth.

Biedrzycki then brainstormed with Jacksonville Zoo veterinarian Yousef Jafarey, D.V.M., and his team to develop a plan: They would cut out the diseased bone, clean out the area and put in bone allografts, antibiotic beads and the placental product “to try to speed things up.”

The giraffe wore a cast on her foot, and three cast changes were performed six weeks apart. The second time, the area was cleaned out a bit more and additional placental compound was applied, Biedrzycki said.

“It was a very big deal,” he said. “I was really impressed with the whole team effort.”

That effort involved the zoo's keepers, its animal health team, an anesthesia crew and many more people performing various duties along the way, Biedrzycki said.

“You also had an army of people massaging the giraffe's neck, another team putting antibiotics in the vein, and the surgery team working on the foot, along with a farrier to help trim the foot,” he said. “There were probably about 30 people altogether working on this giraffe. I think they have the whole procedure down to an art now.”

He said the collaborative effort and range of expertise at the zoo was likely why JoJo did so well with the procedure and continues to improve.

“So far, the outcome is excellent,” he said. “The infection is gone and there is new bone growth at the site showing fusion between the bones, which is really unheard of. She still has some limb swelling, which will take a while to go down. But JoJo seems pretty happy at this stage.”

Jafarey said the zoo was astounded at JoJo's progress since working with Biedrzycki and the UF team.

“The introduction of this new compound has been integral in her recovery and we are excited that our organization participated in this groundbreaking research,” he said.

The material the UF veterinarians have been using started out being used to drive the regeneration of large vessels for heart bypass, McFetridge said.

“I never thought it could be used clinically, as it contains a lot of human maternal tissues, from the placenta, as well as the fetal side of the placenta,” he said. “But after several animal studies, we discovered that there was no negative immune response at all, and that it had a potent healing effect across a range of different tissues.”

Unlike typical biologic treatments that have one response, the placenta-derived material seems to promote healing in several vastly different tissues including bone, blood vessels and skin, McFetridge added.

McFetridge and two of his biomedical engineering department colleagues, Jon Dobson, Ph.D., the J. Crayton Pruitt Family Professor, and Blanka Sharma, Ph.D., an associate professor and the J. Crayton Pruitt Family Term Fellow, have co-founded a company in Gainesville, 42Bio, to commercialize the product for veterinary applications. They recently got private funding to move forward with research facilities at The Hub, UF's business incubator.

“So we're hoping to be able to provide this amazing material more widely, especially as we find out, almost daily, how well it helps heal critical injuries. The healing responses we've seen in the giraffe and the dogs are almost jaw-dropping.”

Read more here.

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