UC Davis veterinarians help horses with laminitis

Veterinarians at the University of California, Davis, School of Veterinary Medicine have announced plans to conduct the first clinical trial of an experimental drug that has shown promise in treating horses stricken with laminitis, a painful and often life-threatening foot-related disease.

Four horses suffering from laminitis have been treated with the investigational anti-inflammatory drug so far. One experienced a complete remission that has lasted for more than a year, UC Davis veterinarians said, and three others have shown some improvement.

A paper on the first laminitis case has been accepted for publication by a peer-reviewed veterinary journal.

"Euthanasia is often the only way to alleviate pain in severe laminitis. We felt that it was important to let the veterinarians and horse owners know that this compound has shown potential as a treatment," said Alonso Guedes, an assistant professor in the School of Veterinary Medicine.

The horses were treated under a "compassionate use" protocol that allows animals to be treated with an experimental drug if no approved alternative treatment exists.

A clinical trial to assess the drug’s safety and establish a tolerable dose for the compound is expected to begin in the spring. UC Davis said further clinical trials would be needed to establish the drug’s effectiveness as a laminitis treatment.

Laminitis is a poorly understood condition involving inflammation of a horse’s nailbed—the connective tissue where the horse’s hoof and lower foot bone join. The inflammation is usually accompanied by swelling, a restriction of the blood supply to that area, high blood pressure, lameness and extreme pain.

Guedes noted that the safe management of laminitis-related pain is one of the biggest challenges for equine veterinarians.

Often, euthanasia is the only humane alternative for alleviating pain and suffering in horses afflicted with the condition. Consequently, the survival rate for laminitis is estimated to be only 25 percent. Very few surviving horses return to their previous levels of activity, and laminitis often reappears.

The experimental anti-inflammatory compound, known as t-TUCB, stems from a discovery made more than 40 years ago by UC Davis entomology professor Bruce Hammock.

Originally interested in finding biological insect control methods, Hammock has since broadened his research to search for biomedical applications. He and colleagues have identified a group of anti-inflammatory compounds that have proven effective in relieving inflammatory discomfort and pain related to nervous system disorders in mice and rats.

In his paper, Guedes reported the case of a 4-year-old thoroughbred mare named Hulahalla that developed laminitis. The horse had been retired from racing following a tendon injury and donated to the UC Davis School of Veterinary Medicine, where it was participating in a study focused on healing tendon injuries using stem cell treatments.

Veterinarians from UC Davis treated the laminitis with conventional therapies intended to reduce inflammation and relieve pain, but the horse only got worse. At the point that the mare was spending most of the day lying down, Guedes became involved.

Before resorting to euthanasia, Guedes and the veterinary team decided to try one last treatment, t-TUCB. After receiving the first dose, the horse remained standing in the stall most of the day, became interested in her surroundings and walked voluntarily.

The mare’s demeanor, posture and mobility continued to improve over four days of treatment, researchers said, and her high blood pressure gradually returned to normal. No adverse effects from t-TUCB were observed, and Hulahalla has remained laminitis-free for a full year.

Hammock said that work aimed at moving t-TUCB and related compounds toward clinical use is advancing in several areas. He and Guedes are working on compounds with potential for targeting pain and arthritis in companion animals. And they are working with UC Davis to move the intellectual property from this research into a company to develop medications for difficult-to-manage neuropathic pain associated with diabetes and nerve injury.