By Dan Ross
Earlier this month, researchers out of the University of Pennsylvania published a breakthrough study which identified several biomarkers associated with shockwave therapy. This study is the first of its kind to identify a possible biological signal revealing shockwave usage–an important development for a therapy that leaves no visible trace, but one that has historically generated welfare concerns due to its analgesic effects.
“Because it's not a drug–it's applied to the surface of the skin–it's just not an easy thing to detect,” said lead researcher Mary Robinson, assistant professor of veterinary pharmacology and director of the Equine Pharmacology Laboratory at the University of Pennsylvania School of Veterinary Medicine, in a press release. “After a lot of trial and error, our study was able to measure changes in levels of five inflammatory factors, some of which we could detect up to three weeks after the shockwave therapy.”
The study was conducted on ostensibly healthy horses. Robinson told the TDN that she and her colleagues will continue to research these biomarkers on other populations of racehorses, including injured horses, injured horses that have received shockwave therapy, and healthy horses in training. For this next step, researchers will dip into the university's large BioBank library of biological samples.
Robinson was also a co-author on a paper published in November proving “proof of principle,” she said, that they were able to detect experimental gene therapy which had been administered via intra-articular injection. Gene doping and its performance enhancing potential is an emerging problem in horse racing. Broadly speaking, the term refers to the twin practices of gene editing–changing animal DNA before they're born–and gene therapy, which refers to the implantation of a piece of DNA into an adult animal to prevent or treat a disease or disorder.
In the following Q&A, Robinson discusses shockwave usage, the implications of her shockwave biomarker study, and her ongoing work in gene doping.
TDN: Can you discuss how the shockwave study was conducted?
MR: The study that was just published is looking at the effect of giving a single dose of shockwave to the front of the cannon bone to 11 healthy horses. What's really novel about this study is we could find changes in the blood that were reflective of these horses receiving shockwave therapy. The biobank is for the next steps–this initial study was more a proof of concept study.
Essentially, what we did, a week before shockwave was given, we took samples each day. After we gave the dose of shockwave, we then collected samples after that dose for up to three weeks. And we were able to see these changes occurring very rapidly, within 24 hours after the shockwave dose, and some of them lasted for up to three weeks.
What that tells me is we probably will need to follow horses out over time. And so, for each individual animal, in order to make these biomarkers make sense, we're going to need to know what their normal profile looks like, and then follow that out over time.
TDN: How did you end up narrowing in on those 10 select biomarkers (of which five indicated shockwave usage)?
MR: That was more a resource limitation than anything else. It's very difficult to do these types of studies on horses, and that maybe speaks to some of the challenges we face in identifying biomarkers. One of the difficult things is there just aren't the resources out there.
One of the ways we narrowed in on those 10 was to see which pro-inflammatory and anti-inflammatory proteins were similar between horses and humans, so that we might be able to use the resources available for humans to try to measure these things in horses. We spent quite a lot of time validating the methods that were used to make sure they would work for horses. And we chose pro and anti-inflammatory factors because we know shockwave causes a very acute inflammatory response. It increases the blood flow to the area.
TDN: What's next in your research?
MR: As you mention, these were healthy horses–they did not have an injury. And we're looking at anti-inflammatory factors which you would maybe expect to be affected by an injury. We need to be able to look at what the effect of an injury is going to do to these factors, and then we need to look at what the effect of giving shockwave on top of that injury is going to do to those factors.
These horses were healthy, but they were not in any type of exercise regimen, so we also need to assess the effect of exercise on these factors–it's well documented that [biomarker] IL-6 that we identified is affected by exercise. So, we'll need to make sure that we take that into account.
TDN: When will you start?
MR: We've already started. We've been working on collecting these BioBank samples for several years now. It was just in the last year and a half that we've been able to quadruple the number of samples that we've collected because of the funding from the Horse Breeders Association. Within the next year, we're going to be starting to make some comparisons using the markers that we've now identified.
TDN: What can you tell us about the BioBank?
MR: The funding for the BioBank is from the Pennsylvania Horse Breeders Association. I was able to start the bank using some internal funds from the [University of Pennsylvania School of Veterinary Medicine] New Bolton Center, and then the PHBA very generously donated money for us to expand the bank, which allowed us to hire an additional person, and get some more freezers, so that we can collect samples from horses at the racetrack and in training at various training facilities.
TDN: The BioBank primarily contains Thoroughbred samples, right?
MR: Yes, although we're actually going to be meeting with some other groups from the Standardbred industry to see if they would be interested in supporting it as well.
TDN: How soon before you possibly narrow in on certain shockwave biomarkers that can be used for regulatory purposes?
MR: I don't know that we'll ever be able to conclusively prove that shockwave had been administered. I think what we hope to do is identify instead biomarkers that suggest that there's something concerning going on in an individual horse. Whether those relate specifically to shockwave or whether those relate to a horse that has some underlying injury–that somebody's trying to cover up or somebody doesn't even know exists–that's what this biological passport hopes to do.
TDN: What are your general thoughts about shockwave usage for horses in training?
MR: Currently in Pennsylvania, we don't allow it on the backside of any of the tracks, and that really is because it's not something that we can detect currently. We do not want to have it risked being used too close to a race, and that's a problem with shockwave: it has a very strong analgesic effect, just as effective as the nerve block when it's used on an injury. The key is, it can be used as a therapeutic, but you have to absolutely rest the horse. You cannot run the horse shortly after it's received shockwave.
TDN: Do you agree with the Association of Racing Commissioners International's model rule requiring a 10-day stand-down, given what we currently know about the analgesic effect?
MR: I do. But there's only one study that's definitively shown that there's an analgesic affect. I think that they stopped around two days in that study, and it's not really clear whether that effect would have lasted longer or not. There's potential that it could have an analgesic effect for a longer period of time.
TDN: What are the implications of gene doping for horse racing?
MR: It's another new way to treat disease. Instead of having to give multiple doses, the whole point of gene therapy is you can give a single dose and have a more permanent treatment. So, when you think of it in that regard, the potential for using it illicitly to try to enhance performance is huge, because a single dose might be able to create a lasting effect. So, I do think it's a serious concern. It's been on the WADA [World Anti-Doping Agency] anti-doping list since 2003. So, our human colleagues have certainly been concerned about it for quite some time.
TDN: Do things that go on in human athletics often makes their way into horse racing?
MR: We certainly have seen that pattern, although the reverse is possible. Some people may feel more comfortable experimenting with horses than with humans. Of course, cost always becomes an issue. But it's possible there are people with the means who are willing to try and win at all costs. So, that's what we're trying to prevent.
TDN: How big an issue is it currently for horse racing?
MR: It's really hard to know at this point. There certainly has been suspicion and discussion and talk about it. I have to say I was pretty skeptical that this was a problem until more recently. Now that the therapies are being approved in humans, they've accelerated the ability for people to actually develop these therapies, so, I think it's something we need to address as soon as possible as an industry.