At the 2025 Applied Sports Science Seminar in Ocala, FL, equine veterinary health consultant Dan Dreyfuss, DVM, spoke about developing an orthobiologic for respiratory use in horses.
Orthobiologics — biological substances naturally found in the body that are used to promote healing and tissue regeneration — are a trending topic these days. “About fifteen years ago, the American Academy of Orthopaedic Surgeons came up with their definition of orthobiologics,” Dreyfuss explained. “The ortho comes from those structures related to the musculoskeletal system, and biologic refers to a naturally-derived product.
“Orthobiologics are a wide variety of substances: they can be cells, cell derivatives, proteins, mRNA species. A wide variety of different molecules, either singly or in combination, can go into these orthobiologics that are found naturally in the body which, used in appropriate concentrations at the appropriate site, may help to speed healing.”
Some common orthobiologic treatments currently being used on horses include platelet-rich plasma, stem cell therapy, autologous conditioned serum, autologous protein solution, extracorporeal shockwave therapy, low-level laser therapy, amnion, and prolotherapy. Most are used for treating musculoskeletal injuries, particularly in joints and soft tissues.
Asthma: Common, and Increasing
Dreyfuss noted, “Asthma is a very common problem in horses, and the number of cases is growing quite rapidly. It’s a complicated disease that can be very difficult to manage. Virtually no two cases are identical, which means that coming up with a treatment for one horse does not necessarily mean it’s going to work for the next one, even if they’re living right next door to one another.
Dan Dreyfuss, DVM.
“As a complicating factor, many of the horses that have equine asthma have comorbidities [two or more diseases at once] or other problems, several of which would prevent them from being treated with some of the pharmaceuticals that are most appropriate for managing equine asthma.”
Currently, equine asthma is commonly treated by reducing airway inflammation and improving airflow, primarily through environmental management of triggers such as dust and mold, and medication via a combination of corticosteroids and bronchodilators.
“There was a whopping total of one FDA Center for Veterinary Medicine pharmaceutical approved specifically for the treatment of equine asthma [Aservo® Equihaler®, ciclesonide inhalation spray] and it was discontinued last year by the company that was manufacturing it,” said Dreyfuss. “So there truly is a need for new ways to manage this common and difficult-to-manage problem in our horses.”
Proteases and A2M
The focus has lately shifted to proteases. “Proteases are enzymes that love to break down proteins — that’s their job,” Dreyfuss explained. “They’ve become a focus for researchers in the human asthma field as well as a target for pharmaceutical development. Proteases themselves can act as allergens; they can trigger horses and people with asthma. They also can then potentiate the inflammation that they themselves might have started in the first place, or was started by a different allergen that a horse may have been sensitive to. They are responsible for the vast majority of the tissue damage that is associated with equine asthma and human asthma. So they have become quite a hot topic for investigation into developing protease inhibitors for treating people with asthma.”
On the equine side, managing asthma through reducing inflammation and inhibition of proteases is now the target of research. “Enter Alpha-2-macroglobulin (A2M), which is a glycoprotein that’s found in the blood of all vertebrate species, and a wealth of invertebrates as well,” said Dreyfuss. “It’s part of the innate immune system and its purpose in life is to fight foreign invaders, principally viruses and bacteria. Its principal mechanism for preventing their proliferation is through the inhibition of proteases — all four classes, non-selectively.” It also acts as a naturally-occurring anti-inflammatory molecule.
Dreyfuss and his team developed a protocol for nebulizing A2M to horses with equine asthma. “We wanted to do an initial small pilot safety study to make sure we weren’t harming any horses when they were nebulized,” he explained.
The horses were assessed with a weighted clinical scale to evaluate their status. They went through a series of six nebulizations at 48-hour intervals. Each horse’s temperature, pulse, and respiration were monitored, both pre-nebulization and one hour afterward, to see if any significant changes had occurred. Bloodwork was done, and seven days after the last nebulization — day 17 — their weighted clinical score was again assessed.
“From a safety perspective, there were no significant signals. Importantly, no horses fell down and went boom. No horses had significant changes in their temperature, pulse or respiration, no horses developed epistaxis [nosebleeds] associated with nebulizing the Alpha-2-macroglobulin.”
What was interesting was that while all the horses were very mildly affected by asthma, seven of the eight demonstrated an improvement in their scores at the day-17 follow-up. Dreyfuss was encouraged. “There was enough positive evidence to support doing a larger pilot study.”
Fifty-four horses at eight different sites around the U.S. were recruited and evaluated. “Of the fifty-four horses, there were twenty protocol deviations, unfortunately, so those horses had to be thrown out.” Of the remaining 34 horses, 30 of them (88.2%) showed a positive response.
Looking Ahead
So what does all that mean? “It doesn’t mean this is a cure for asthma,” Dreyfuss cautioned. “It doesn’t mean it’s going to work on every horse with asthma. It’s very early in the process, but it has demonstrated some very encouraging clinical improvement in a large percentage of the horses that have been exposed to nebulization with A2M.” As a result, a collaboration with several veterinary schools in the U.S. and one in the UK is taking part in a larger blinded, controlled, randomized study using client-owned horses that was launched in the spring.
Overall, Dreyfuss advises cautious optimism. “When new products come around, or new uses for existing products, it is really important to critically evaluate the data that’s in front of you. It takes time and a lot of money to get these trials done.”
“There is no cure for osteoarthritis,” he noted as an example. “There is no comprehensive single thing that’s going to fix articular cartilage and restore it to what it was like before you start putting weight on it. And there’s no cure for equine asthma — but please keep an open mind.”
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