New Horizons in Equine Joint Care with Injectable Polyacrylamide Hydrogel

Discover groundbreaking insights as we chat with Dr. Jason Lowe about innovative research on equine joint health, recently spotlighted in JAVMA. Prepare to have your perspectives shifted on the veterinary approach to joint disease, inflammation, and immune responses, as Jason unveils the results of a study on 2.5% injectable polyacrylamide hydrogel. The study findings reveal an intriguing, macrophage-driven inflammatory response that is transient and stays within normal lab ranges, resolving within 90 days. We explore how this treatment remarkably becomes one with the joint, encouraging the formation of a new synovial cell layer, and we consider the implications for equine sports medicine.

Our conversation doesn't stop at the cellular level; we also tackle the practicalities of equine joint management. Emphasizing the critical role of accurate diagnosis prior to intervention, we discuss how a deep understanding of polyacrylamide hydrogel can dramatically enhance joint function and how adopting a proactive treatment strategy can boost the performance and longevity of equine athletes.

Open access article: https://doi.org/10.2460/javma.23.10.0553

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Transcript

Sarah Wright: 0:00

You are listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode we chat about histologic and cytologic changes in normal equine joints after injection with 2.5% injectable polyacrylamide hydrogel with our guest Jason Lowe.

Lisa Fortier: 0:24

Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today, we have my friend and colleague Jason joining us. Jason, thank you so much for being here with us today, all the way from New Zealand.

Jason Lowe: 0:37

You're welcome, happy to be here.

Sarah Wright: 0:40

All right, let's trot on over. Your JAVMA article discusses how histologic and cytologic changes in normal equine joints after injection with 2.5% polyacrylamide hydrogel and how that revealed low-level macrophage-driven foreign body response. Please share with our listeners the background on this study.

Jason Lowe: 1:01

Yeah, thank you. Yeah, I first came across Arthramurth around 2014, and my colleague had brought it back. There was a couple of interesting early abstract publications, but we had some questions around what it was doing in the joint. Obviously, before you give it to your patients, you want to know stuff like that. We were also looking at a regulatory process to get it registered as a veterinary medicine. In Australia and New Zealand we don't have a device category like you do in the US. So, yeah, we had some specific questions from ourselves and from the regulators that we were trying to answer with this study.

Sarah Wright: 1:43

And then can you also share with us some of the pivotal results from this study.

Jason Lowe: 1:49

Yeah, I think what was most interesting to us was this transient inflammatory response you see in the synovial fluid in response to the gel. So you're getting this what's described as a typical foreign body reaction. So macrophage is essentially a macrophage-driven response to the gel and over the 14 days to 42 days the time points in our study, although we also went out to 90 days with one of the patients you'll see this increase in macrophages. Now, the important thing is it never goes above laboratory reference ranges. So it's not a severe reaction, it's just this low-grade, mild macrophage reaction and certainly by 90 days that is completely resolved and the joint is back to normal physiological parameters. I think the second most interesting thing was how the gel is fully integrated into the subintimal space of the synovial membrane. There's no free gel sitting in the cavity. There's no. It gets completely adsorbed and you end up with this brand new de novo synovial cell layer, the intimal layer of type A synovial sites, overlying the gel. I think those were the two critical things for us.

Lisa Fortier: 3:16

Yeah, it's fascinating, nando Jason. We've had these conversations before in veterinary and human medicine in general. The word inflammation really needs to be redefined. So does the idea like, ooh, macrophages, that's terrible. That means you're having a foreign body response. That is just a sledgehammer approach to any type of cellular infiltrate.

Jason Lowe: 3:42

Yeah, you're right, and I heard somebody recently talk about the immune system and the immune response and I think, when I sort of look back on my career as a veterinarian, it's that immune response is the body's natural response to stuff which is so important and healing and, like you say, we've had this real focus on moderating that or eliminating that response, and we do. We need to shift our thinking in that.

Lisa Fortier: 4:09

Yeah well, good luck changing that culture. I know you were a clinician for a long time and still practice to some extent. What sparked your research interest in this area of equine sports medicine?

Jason Lowe: 4:22

Yeah, it's a great question. I think it was just being inquisitive. I was dealing with a lot of thoroughbred race horses in my practice here in New Zealand. I was also dealing with a lot of high-end English performance horses and I think it was just that frustration around the limited products that we had available and the results. It was literally 50-50. I felt in my practice as to whether you're going to get a good response ie the horse would become sound, sound enough to compete or whether you're going to get a bad response and that horse was backed out of competition or potentially retired. So I think that's really, for me, was what said hey, we've got to be doing something better, something different to what we were doing. Sort of early 2010s, we were using IRAP. Stem cells were sort of coming along and people were talking about them, but this was the opportunity to look at something new again, which was what really intrigued me and started using it in my patients and just saw the results and that's what really pushed me on to look at it further.

Lisa Fortier: 5:39

And I understand and appreciate that. One of the limitations of this study is that they were done in normal horses, which is where we should start. But of course, similar to us thinking, ooh, inflammation or cellular infiltrate is bad, we don't really understand the disease process either. Are we injecting? You were saying about 50-50 response. We don't really understand if we're injecting in the beginning of the disease or the middle of the disease, a quiescent form of the disease. Do you have any insight in that from your clinical practice or your research?

Jason Lowe: 6:11

Yeah, well, I think the classic for that to me was IRAP, when that came onto the market and I had some amazing results with that product and other times some really disappointing results. And I think to me, as I develop my understanding, just that that diurnal rhythm and pro-inflammatory cytokines and, like you say, your timing of intervention can be so critical as to the response you get and I think as well the sort of the team approach, because it's not just putting something into the joint or it but it's also changing the training and trying to get horse owners and trainers to think differently around stuff and taking that holistic approach to rehabilitation and treatment. And again, I think that's where this product, the 2.5% polyacrylamide, just gives us another tool in the bag to, like you say, try and better understand the nature of the disease and that timing of intervention which is critical.

Lisa Fortier: 7:12

Yeah, so much to learn. Well, we'll be busy for decades to come.

Jason Lowe: 7:18

Hopefully.

Lisa Fortier: 7:19

This is a really important manuscript for this product. There's been some controversy around it and its mechanism of action and all those sorts of things, and we're very grateful that you shared it with us at Javma. Why did you choose to submit your manuscript to Javma?

Jason Lowe: 7:33

Because of you, Lisa, I heard your talk at the Regenerative Medicine Conference in Hawaii and I was just really impressed with the vision and the philosophy that you talked about in publications.

Jason Lowe: 7:51

And this is my third paper now on the product, on this particular product, and I think that's where, to me, choosing a journal which just is about disseminating the information and having that conversation when you start writing an article. It can be very difficult, it can be a lonely experience and you want to feel like you've got some open communication, because I think the review process and peer review is incredibly important, obviously, and it always makes a better manuscript, but it's also having a journal that, instead of being the gatekeeper, somebody that's prepared to understand, I guess, where clinicians are coming from, because I think there's difference between clinical settings and research settings and I think there's so much valuable information from clinical practice that perhaps gets lost because the barriers are too difficult, not to say we shouldn't. Yeah, you got to keep those standards absolutely, but, like I say, I like the philosophy and vision that you talked about that day.

Lisa Fortier: 9:05

Well, thank you, I wouldn't have asked that question if I knew that was the answer. That's a little embarrassing, a little self fulfilling, but you know we've worked really hard to change that culture and you're right, the review process is so important and to have a constructive review and teaching people how to be reviewers. You're not a copy editor, you're not there to be the gatekeeper or the gotcha how to tear down a manuscript, and that can be a difficult process to change as well. So thank you for noticing that We've been trying really hard.

Jason Lowe: 9:38

Yeah, yeah, no, that's exactly what it's about.

Lisa Fortier: 9:42

When Sarah asked you a little bit ago what were some of the pivotal findings but oftentimes in writing you're like huh, I didn't expect that. What was the most surprising finding from your article?

Jason Lowe: 9:54

Yeah, I think it really does come back to that low grade typical foreign body response and it's so well reported in human medicine, obviously, where they've been dealing with implants and prosthetics and stuff for a long, long time and it just I don't think it's well.

Jason Lowe: 10:14

Certainly my reading it was.

Jason Lowe: 10:16

I didn't really understand that from a veterinarian perspective and I'm sure the surgeons listening to this are cringing because I'm sure they are aware of it around plates and screw implants and stuff.

Jason Lowe: 10:28

But I think that to me and like you say, coming back to the inflammation, I think what was really intriguing was that it's macro farge driven.

Jason Lowe: 10:38

It's a macro farge led response to this foreign body, but it can be low grade and once the body recognizes that the product isn't an irritant, it's not a problem for it, it's quite inert and it just fully integrates and everything calms down. And, like I say, by 42 days we started to see this sort of calming down of the response and by 90 days there's literally no ongoing response to it. So I think, yeah, the fact that things it's a low level, macro farge driven response and I think it's these macro farges which are pivotal in our understanding going forward around the OA disease and I think the other critical thing for me was perhaps some of the early literature, I think, sort of perpetuated this concept that there was free gel sitting in the cavity, and this study absolutely categorically shows that there's no free gel sitting in the cavity. It is fully integrated into the sub-intimal space. And I think that's the other real interesting point to clarify in the literature.

Sarah Wright: 11:50

Sounds like it was a little bit of a myth buster study then too.

Jason Lowe: 11:59

Yeah, I think that's I mean when I gain my basic understanding of publications, you know, are we repeating something that's been done before, to show that it's repeatable, which is actually really interesting? And but also, yeah, what sort of adds to the literature? Right, what is the next stage of that story? And I think this, this is a nice additional to what's been published so far. I think, as to your point earlier, lisa, the mechanism of action, I think we've still got a little way to go with this product, but I think this paper starts to unravel that a bit. And I think again, yeah, we did the study back in 2015, 16,. What really pushed me to publish it now was the, this new understanding of the importance of macrophages and these activated macrophages in the joint, and I think that's happening not only in veterinary medicine, but a very strong recognition in human medicine, and you look at the work of Steph Dakin at Oxford University and the arthritis center in Edinburgh.

Jason Lowe: 13:06

I think this is where the real, the real exciting stuff's going to happen. This is hopefully a nice progression towards that.

Sarah Wright: 13:15

And for those of you that are just joining us, we're chatting with Jason about joint injections with polyacrylamide hydrogel. So, jason, how did your advanced training prepare you to write this manuscript?

Jason Lowe: 13:27

I think nothing prepares you to write a manuscript. I think every time I've done it it's been a different experience. I think the more you do, the better you get at it. But it is daunting and, like I say, I'd highly encourage anybody that's thinking about it to do it, because I think all information is valuable. It doesn't have to just prove a theory. It can disprove stuff as well. So I think, yeah, just get on and do it. Talk to people, get the right people on your team that can contribute. And I think that's a real important thing too is having people that can help you actively review the manuscript to make it better and help you be critical of your own work, because what happens when you're writing 10,000 words and you keep reading it? You just you stop seeing the detail, and it's important to be aware. So I think the other thing around that is your own ego. You have to sort of put that in a box and be prepared to be knocked around a little bit, but realise that it's for the greater good.

Sarah Wright: 14:43

I remember for my first manuscript, my co-authors were so supportive and I think that really is what shaped me as a scientific writer. I think had I had coworkers that were maybe not as invested, I would have been discouraged. But my co-authors were so encouraging and they're like this is great, now here's how we can make it better. And of course you get it back and it's all red with track changes and you're like, oh dear, but it serves a purpose.

Jason Lowe: 15:06

I was just going to say. I think it's exactly that. It's that action learning, isn't it? What did we do well? Can we do better in an approach?

Lisa Fortier: 15:14

My first manuscript I wrote was on Plantar P1, lesions in horses and arthroscopic removal of them and return to racing. And there were probably four other manuscripts that had smaller series, not as big a distribution, not as many standard breads, and so I thought, well, why am I going to repeat all that information? They can just go to my references. So I had like three. This is old typewriter days, Sarah, this wasn't something on the computer. I had like three pages and I gave it to the professor and they wrote on there well, this is a good start. Now more, more, more. Yeah, very encouraging.

Jason Lowe: 15:50

For those days, lisa trying to print stuff out as well. The prints are failing.

Lisa Fortier: 15:56

We tried to play Stump the Chump with Sarah and we'll show her things in the office Like do you know what this is? Nope, never seen that before. It's actually pretty funny. I can do the same to us, but she's too nice.

Sarah Wright: 16:09

I do more research. I'm a nineties kid, so anything before that. I'm like I don't know what that is, or maybe I heard of it, so yeah, but going back to your manuscript, this next set of questions is going to be really important for our listeners. So what is one piece of information the veterinarian should know before discussing joint injections with polyacrylamide hydrogel with a client?

Jason Lowe: 16:35

I think the critical thing is accuracy of diagnosis.

Jason Lowe: 16:39

This is a really great product if you have articular disease and then the veterinarian really needs to be aware and I think we've got some gaps to fill in around that mechanism of action.

Jason Lowe: 16:50

But understand that the product is so, it's undergoing this integration process, it's undergoing a low grade foreign body response. So how this information changed my practice was I now back off the horses I think we've got. We're all in that sort of mindset that oh, let's get a medication and as close as we can to racing or competition but outside the withdrawal time, and just keep pushing this horse through from so many aspects of welfare but also disease and longevity. We need to be backing off these horses, understand the disease, back off the horses, treat them with something that can help rejuvenate or regenerate or improve the quality of the joint and its function and then slowly work the horse up again. We shouldn't be exercising lame horses and I think that's, to me, is what the veterinarians need to understand with this product. It offers them something different to the traditional Trimesin alone, hyaluronic acid options and to really get the head around the fact that it's integrating into the joint and inducing a response in the joint to help that joint environment.

Sarah Wright: 18:08

And then on the other side of the relationship, what's one thing clients should consider around joint injections with 2.5% polyacrylamide hydrogel.

Jason Lowe: 18:21

Yeah, again, I think it's probably in the same tangent to me as we're talking about before timing of intervention Really consider proactively managing your horse.

Jason Lowe: 18:34

And I think, again, a tool like this that we get into our treatment box suddenly allows us to look at the horse early on in the competition season and to think about and even from a year ago I do a lot of yelling, repository work and say, you know, we're identifying these horses really early on in their careers where they could get potential issues and so saying, ok, we know that that horse could have an issue there, so let's get in and manage it early and let's keep, I can say, getting your head around the fact that a product that does that you're not just suppressing pain and inflammation and trying to get the most out of it, you're actually managing the horse better.

Jason Lowe: 19:17

And I think what we've found and it's been really interesting the shift I've seen in our trainers and owners here in Australia and New Zealand, because they were very much of that mindset what can I get close to competition, whereas now they line the horses up very early on in the season and we see July, august, because we're opposite to you guys, so now these horses are coming in for early for spring carnival prep and they'll treat them really early on and they just become much easier horses to manage and I think that that proactive approach and I think that's the mindset change we've seen in the trainers and owners here and I think that that's what you'll start to see in the US and other markets as well.

Lisa Fortier: 20:04

Yeah, I think that's really critical. I love how you put it's not about joint injection in horse industry, especially racing in general. Oh, you're trying to kill their pain so they can race more, but you're really managing their joints for longevity and welfare of the horses. You said so. I really like how you put that. It is overall management and a really wonderful shift.

Jason Lowe: 20:27

Yeah, thank you. Yeah, and it's been. We've had some great conversations here with the regulators around racing and stuff and they're recognizing as well how it's just that proactive approach as much more beneficial and, like you say, we all understand the pressures we're under from a welfare point of view. So it's exciting Very good, Very good.

Lisa Fortier: 20:50

Well, thanks again, Jason. As we wind down a little bit, we try to ask this mostly funny but kind of personal question what is the most interesting or the oldest item in your desk drawer?

Jason Lowe: 21:03

I've actually got a very old bottle with a note in it that my father gave me. He found it on a beach in New Zealand a long, long time ago and I can't get the note out and I don't want to smash the bottle. So it just remains this mystery of who is the note for or from, and what it was doing in a bottle on a beach in the top of the South Island of New Zealand. But we'll never know. But it's quite interesting.

Sarah Wright: 21:32

Message in a bottle. I don't know if I would not be able to look at that. I don't know if I'd have the self-restraint to just let it sit there.

Jason Lowe: 21:41

Yeah, well, you're like my young daughter. She wanted to smash it and get it out and dig it out. So I had to say no, yeah, because I just think it's really interesting.

Sarah Wright: 21:51

That's pretty cool, though we have not gotten that answer yet, so thank you for sharing that with our listeners. Just thank you again, jason. We appreciate your time and for your contribution to our journals, so thank you.

Jason Lowe: 22:04

You're welcome. Thank you, Sarah.

Sarah Wright: 22:06

And to our listeners. You can find Jason's article on our journal website or using your favorite search engine. I'm Sarah Wright with Lisa Fortier. You want to thank each of you for joining us on this episode of the Veterinary Vertex podcast. We love sharing cutting edge veterinary research with you and we want to hear from you. Be sure to leave us a rating and review on Apple Podcasts or whatever platform you listen to.