By Mark Andrews

For the first time, researchers have unveiled an intervention that appears to slow down the progression of osteoarthritis (OA). 

A clinical study conducted jointly by the Swedish University of Agricultural Sciences (SLU) and the University of Gothenburg (UGOT), Sweden, has yielded remarkable results. Horses afflicted with OA, treated with a novel drug combination, not only achieved freedom from lameness but also experienced a simultaneous inhibition of joint tissue degradation.

OA is a degenerative disease involving the whole joint. It arises from the deterioration of joint cartilage and the underlying bone structure. This condition is the primary cause of joint pain and lameness in horses. Racehorses often become lame early in their careers, and every year many horses retire due to the disease.

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New Drug with Treatment Potential

The new potential treatment for OA stems from a long-term collaboration between researchers at SLU and UGOT resulting in a series of basic science publications. Through extensive cell culture studies, the researchers had been able to evaluate and present a drug combination consisting of a local anaesthetic drug and an anti-inflammatory drug (sildenafil), in extremely low concentrations. When coupled with glucose, this combination demonstrated the capacity to rejuvenate and repair damaged cartilage cells, known as chondrocytes, extracted from horses affected with OA.

“We have successfully demonstrated the drugs’ potential in receding inflammation and in restoring derailed chondrocytes from OA horses. Such restored cartilage cells began to produce more matrix molecules, which are important building blocks of cartilage tissue. This further strengthens the drug combinations’ potential to cure osteoarthritis," says Elisabeth Hansson, professor at the Sahlgrenska Academy, University of Gothenburg, who is one of the research leaders in the collaboration.

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New Method for Diagnosis 

The research team has developed assays to screen horses’ synovial fluid from the joints and diagnose OA much earlier, i.e., even before the clinical indications of OA. This was indispensable for clinically testing the drug in horses. They have found two biomarkers that are elevated in both synovial fluid and blood in horses with OA.

These biomarkers (BGN262, which reflects subchondral bone degradation, and COMP156 which is associated with articular cartilage degradation in equine early OA) have been crucial in the development of the new drug treatment.

The current clinical study, published in the journal Osteoarthritis and Cartilage Open, uses these assay methods both to diagnose the disease and to measure the efficacy of the new drug treatment.

“With the aid of these biomarkers, we can now diagnose the disease in an early stage (which was not possible previously), measure the efficacy of the drug, and also screen for the drugs’ side effects,” says Eva Skiöldebrand, professor at the Swedish University of Agricultural Sciences.

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Randomized Clinical Trial

In this study, the new drug combination was tested in a randomized triple-blinded controlled clinical trial. The study was conducted at Hallands Djursjukhus (Kungsbacka Hästklinik). Principal investigator, Kristin Abrahamsson-Aurell, was responsible for the study with Cecilia Grahn as the treating veterinarian.

Twenty lame trotters with mild radiological changes in the carpal joint were included in the study. The horses were randomized into groups for treatment with the novel drug combination or with a standard treatment (betamethasone — Celeston® bifas®). The horses were followed up for 60 days after treatment.

“The horses treated with the new drug combination became free from lameness. The drug treatment efficiently lowered the analysed biomarkers’ levels in the synovial fluid when compared to the horses that received the control substance. The drug intervention did not cause any side effects in this study. Moreover, several of the treated horses remained sound during the follow up period, which gives great hope for the future of the drug as a disease-modifying agent. This will have a tremendous positive impact on horse welfare,” says Skiöldebrand.

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Potential for Treatment in Humans 

In Sweden, OA is the most common form of arthritis in humans, characterised by chronic pain and loss of mobility and affecting millions of people worldwide. Currently there is no cure for OA. Moreover, the available drugs on the market can only reduce pain and limit inflammation in the joint.

“Horses and humans are genetically very similar. Horses develop OA spontaneously, which makes the horse an excellent model for studies of OA in humans. Additionally, the biomarkers that were identified and evaluated in the clinical trial are identical in horses and humans. Therefore, the biomarkers and the analytical methods are equally relevant in human OA," says Skiöldebrand.

The research team has a patent for the new drug combination and aims to commercialize it as a licensed drug for horses with OA, starting in Sweden. They will now also seek authorization to conduct a clinical trial of the drug treatment in humans.

For more details, see A randomized, triple-blinded controlled clinical study with a novel disease-modifying drug combination in equine lameness-associated osteoarthritis - ScienceDirect

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Published with the kind permission of Mark Andrews, Equine Science Update. 

Photo: Dreamstime/Les Palenik