For the first time, an intervention that appears to slow the progression of osteoarthritis (OA) has been presented.
In a clinical study from the Swedish University of Agricultural Sciences and the University of Gothenburg, OA horses receiving a new drug treatment became completely lameness-free, with simultaneous inhibition of joint tissue degradation. Exploring these drug treatments for human OA intervention is now being considered.
Osteoarthritis (OA) is an inflammatory disease of all joints that affects animals and humans. It is the most common cause of lameness and joint pain in horses. Racehorses are often crippled early in their careers, and every year a large number of horses retire due to the disease.
New drug with healing potential
This new potential treatment for OA is the result of a long-term collaboration of researchers at the Swedish University of Agricultural Sciences and the University of Gothenburg, resulting in a series of basic science publications. Through cell culture studies, researchers can evaluate and present a drug combination consisting of a local anesthetic and an anti-inflammatory drug (sildenafil), in very low concentrations, which when combined with glucose can restore slipped cartilage cells (i.e. chondrocytes) in horses. OA.
“We have succeeded in demonstrating the potential of the drug in relieving inflammation and recovering derailed chondrocytes from OA horses. Such restored cartilage cells begin to produce more matrix molecules, which are important building blocks of cartilage tissue. This further strengthens the potential of drug combinations to cure osteoarthritis,” said Elisabeth Hansson, professor at Sahlgrenska Academy, University of Gothenburg.
New diagnostic method
The research team developed a test to screen horses’ synovial fluid from joints and diagnose OA much earlier, even before OA was clinically indicated. This is indispensable for clinically testing drugs in horses. The current clinical study, published in the journal Osteoarthritis and Cartilage Open, uses this testing method to diagnose disease and measure the efficacy of new drug treatments.
Two biomarkers were increased in synovial fluid and blood in horses with OA. These biomarkers are very important in the development of new drug treatments.
“With the help of these biomarkers, we are now able to diagnose diseases at an early stage (which was not possible before), measure drug efficacy and also screen for drug side effects,” says Eva Skiöldebrand, professor at the Swedish University of Agricultural Sciences.
Randomized clinical trial
In this study, the new drug combination was tested in a three-blind randomized controlled clinical trial. The study was conducted at Hallands Djursjukhus (Kungsbacka Hästklinik). The lead investigator, Kristin Abrahamsson-Aurell, was responsible for the study with veterinarian Cecilia Grahn as the treating veterinarian. Twenty paraplegic runners with mild radiological changes to the carpal joints were included in this study. Horses were randomized into groups for treatment with the new drug combination or with standard treatment (Celeston bifas drug). The horses were followed up for 60 days after treatment.
“The horses treated with the new drug combination became lameness-free. The drug treatment efficiently lowered the levels of the analyzed biomarkers in the synovial fluid when compared to horses receiving the control substance. Drug intervention did not cause side effects in this study. In addition, some of the horses treated remained healthy during follow-up, which provides 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.
Potential for treatment in humans
In Sweden, OA is also the most common joint disease in humans, especially among the elderly. About one in four people over the age of 45 has osteoarthritis. Currently, there is no cure for this. Also, the drugs available in the market can only reduce pain and limit inflammation in the joints.
“Horses and humans are genetically very similar. Horses develop OA spontaneously, which makes them an excellent model for studies of OA in humans. Moreover, the biomarkers identified and evaluated in clinical trials are identical in horses and humans. Therefore biomarkers and analytical methods are equally relevant in human OA,” said Skiöldebrand.
The research team owns 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 also now seek authorization to conduct clinical trials of the drug treatment in humans.
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