WEBVTT
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00:00:40.000Welcome to Epic Award-winning Veterinary Vertex, the AVMA Journal's podcast where we delve in behind-the-scenes look with manuscript authors.
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00:00:44.320I'm editor-in-chief Lisa Fortier, joined by Associate Editor Sarah Wright.
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00:00:59.600Today we're discussing recurrent clinical signs of thyraco lumbar disc herniation following multiple chondroitinase ABC intradiscal injections versus routine surgical management with our guests, William Tamaro, Nick Jeffrey, and Paul Freeman.
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00:01:02.880Thank you for joining us, William, Nick, and Paul.
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00:01:05.599Hiya, I'm taking care of us.
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00:01:07.840All right, Paul, let's start with you.
00:01:07.840 -->
00:01:16.879What motivated your team to investigate chondroitinase ABC as a potential strategy for reducing intervertebral disc herniation in dogs?
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00:01:53.680Yeah, I think it was something that we thought uh might theoretically be um uh be happening because uh, you know, understanding how the chondroitinase ABC is potentially working in the nucleus pulposus of the discs, you might think that it's kind of uh equivalent to a chemical fenestration in terms of reducing the volume of the nucleus pulposus that remains inside the disc and therefore potentially making it less predisposed to uh to extrude in the future.
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00:02:04.159So um that's why we decided to try and come up with a methodology that would allow us to look at that and see uh if we could get some evidence that it was actually happening.
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00:02:06.079This is such an interesting treatment.
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00:02:12.800Nick, for listeners who may be less familiar with the treatment, what is chondroitinous ABC and how is it thought to work?
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00:02:39.680Um it's a bacterial enzyme that uh digests chondroin sulfate proteoglycans, which are a major component of the intervertebral disc nucleus, and basically it digests that uh those products and uh stops the nucleus from retaining the water that it would normally retain, um, because that's the main function of the chondrotin sulfate proteoglycans.
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00:02:51.199Nick, will I have you uh we've I'm an equine surgeon, and we still sometimes use the model of collagenase uh into the tendon, and dang it, it's hard to control.
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00:02:56.719How did you what are the nuances of volume and dose and needle size?
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00:03:00.240How do you really control this chemical fenestration?
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00:03:11.520Yeah, so I it it it because it the substrate is relatively limited in in where it turns up anatomically, it's not such a worry as collagenase.
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00:03:22.719Uh collaginase has been used in the spine and um it it was hard to manage because it if it got into the vertebral canal, it was quite damaging.
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00:03:35.680And uh chondroitin sulfate um sorry, chondroitinase is less dangerous because we know that even if you put it into the spinal cord, it's it's not highly damaging or anything.
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00:03:39.680In fact, it can be used as a treatment for spinal cord injury as well.
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00:03:50.479Um, and so it tends to restrain itself because it can't get out from where where we put it because it can only digest the condroitine sulfate pietocarcans.
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00:03:52.000Oh, interesting.
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00:04:00.639William, can you describe how the study was conducted and how chondroitase uh treated dogs were compared to dogs receiving routine management?
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00:04:02.240Yeah, of course.
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00:04:12.080Um, so we started off getting enrolling dogs into the study, and we had two arms, the the chondroitinase arm and the surgical arm.
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00:04:20.160Um we aimed for about 50 chondroitinase dogs and 100 surgical dogs from both Texadyn M and Cambridge.
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00:04:31.519Um and we both dogs or both sets of dogs had to be uh acutely non-ambulatory within 48 hours, present to the hospital within 72 hours.
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00:04:34.480All of them had to have deep pain perception intact.
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00:04:43.519And then one of the stipulations was they had to regain independent ambulation, which we defined as the ability to take 50 steps unassisted.
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00:04:47.839Um, and then they had to have at least uh six months of follow-up time.
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00:04:55.199Um, one of the specific inclusion criteria for the chase dogs was they had to be less than 15 kilograms.
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00:04:59.680Um, and then with the surgical group, we used time matching.
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00:05:08.240So the matched uh surgical dog had to have their surgical procedure within 30 days of the uh chase procedure.
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00:05:25.680Um and then we touch on it a little bit in the paper, but uh the difference in fenestrations, we tried to match up the the breeds and fenestrations, but those criteria were relaxed in order to get the appropriate sample size as long as the uh time matching was met.
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00:05:39.199Um and then what we did was me and Joe both reached out to the owners for follow-up via uh phone call or texting and just had a simple questionnaire basically asking, were there signs of recurrence?
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00:05:40.079Yes or no?
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00:05:46.480If they did have signs of recurrence, we uh further elaborated on that, asking what were the signs?
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00:05:48.720Did they seek veterinary care?
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00:05:50.879Um, was treatment pursued?
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00:05:54.720And then if treatment was pursued, did they subsequently recover?
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00:05:57.920And did they have any recurrences after subsequent treatments?
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00:06:04.480Speaking of recurrence, Nick, what were the most important findings regarding recurrence rates between the two treatment groups?
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00:06:11.839Uh well, somewhat to our surprise, there was quite there was a big difference between the two groups.
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00:06:16.160Uh the recurrence rate in the chondroitinate treated group was way less.
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00:06:28.319Um, it depends on how you analyze the recurrence, but it it's roughly 70% reduction in in recurrences in the chase treated dogs versus the surgery.
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00:06:56.000So the reasons for that, um, which might be one of your follow-up questions, I guess, but the the reasons for that could be because of how the chase works, but it could also be partly to do with the number of fenestrations that were carried out in the surgical group, um, because uh up to three discs were fenestrated in the surgical group, whereas we were treating four in the chase group.
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00:07:22.800Um but the idea was really that we're trying to map, we're trying to compare against you know what's actually done in real life um in terms of surgery, because not every dog gets multiple level fenestration, and so we were using dogs that had been treated to the clinician's tests uh judgment at each at each um for each individual case.
00:07:23.519 -->
00:07:27.439How might this condroitase ABC compare now?
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00:07:32.079How might how might it go to cervical or thoracolumbar intravertebral discs?
00:07:32.800 -->
00:07:39.839So we're already treating fluorocolumbar discs, um, and we can do that with just fluoroscopic guidance.
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00:07:51.279For the cervical ones, we have started treating them here at ANN, but it's a little bit more involved because there's a lot of structures you can't see on fluoroscopy that you don't want to put needles into.
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00:07:57.920And so we've been using ultrasound guidance um to place the needles in the disc.
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00:08:00.240Um, but we we have started doing it, yeah.
00:08:00.800 -->
00:08:07.680And and how do you think the recurrence rate is in those compared to standard surgical fenestration?
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00:08:11.839Uh yeah, that uh we haven't got enough follow-up on that.
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00:08:27.600Um the the this the dogs that we've treated in the neck are a bit of a different group because we're we're targeting it to a single disc, for one thing, um, because we're using MRI to localize it.
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00:08:52.000Um and the reasons for choosing chondroitinase are often to do with a non-invasive or less costly part of it, because most of these cases would be recommended to get surgery, but for some for some reasons the owners turned down surgery, and so they're they're a bit of a different they're a bit of a different um case selection.
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00:09:10.720I think the other the other thing to add there is that fenestration is is much less commonly practiced in the cervical region than the thoracolumbar region anyway, um, because people don't well we don't have the evidence, first of all, that it's effective at reducing recurrence uh in the cervical region.
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00:09:29.120Uh I mean there's not really any reason why it wouldn't be, but people tend to worry a bit more about creating instability in the neck by fenestrating discs in the neck, and we haven't got those studies that really tell us whether it's um entirely safe thing to do in the in the cervical region.
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00:09:46.320But um I just wanted to add that uh in terms of the thracolumba region, which is where uh you know we people do worry about recurrence because that's where the dogs suffer an extrusion that potentially kills them or leads to them being killed.
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00:09:54.480Um and often if they have a recurrence, that's the the tipping point for the owner to say we're not going to go through this again.
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00:09:59.600Um, so reducing recurrence of of those is is, I think, a lot more important.
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00:10:21.120And the other thing is in terms of comparing the surgical and and chondroitinase groups, you know, as Nick sort of alluded to, in an ideal world, if we really wanted to show that chondroitinase was better than fenestration, we'd have to have compared a group of dogs that had four discs injected with a group of dogs that had four discs fenestrated.
00:10:21.120 -->
00:10:23.440But I don't think that was ever the aim of the study.
00:10:23.440 -->
00:10:30.080The aim was to because injecting a disc with chondroitinase is so much easier than doing surgical fenestration.
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00:10:49.120What we wanted to show was that if we could have a if we found a significant reduction in the current rate in dogs that had four injected discs compared to dogs that had surgery with any number of fenestrations, that would be evidence that it was acting prophylactically.
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00:10:53.200Um and and and that's really all we were trying to find out, I think.
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00:10:55.440Um is that is that fair, Nick?
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00:10:56.879Yeah, I think so.
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00:11:06.080Yeah, I think the way that yeah, I mean, I the way that you suggested it to me was we've got all these cases, we might as well do this study.
00:11:06.080 -->
00:11:18.559And then I sort of added on, we might as well compare them against surgery cases, and so that was the origin of it, really, that we had we have the case material available and we might as well just look back.
00:11:18.559 -->
00:11:44.240It it to set up a a prospective trial would obviously be ideal, but as you say, I think you know, once you start saying to people you must do four fenestrations, and they're operating at 11 o'clock on a Friday when they're at PM, where after they've done another three cases, and then they say you've got to do four fenestrations, they people start not wanting to join in with your study.
00:11:44.240 -->
00:11:48.080And um I I think that that's when it becomes problematic.
00:11:48.080 -->
00:11:58.559But it could be set up in a more ideal way, but this is like a preliminary sort of look to see if there's any evidence for prophylapsis.
00:11:58.559 -->
00:11:59.120Yeah.
00:11:59.519 -->
00:12:03.039We've talked a lot about the clinical decision making when it comes to this treatment.
00:12:03.039 -->
00:12:05.519Now I want to talk about the clients too.
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00:12:14.159All how might these findings influence conversations between veterinarians and owners when discussing treatment options for dogs with intravertebral disc herniation?
00:12:14.799 -->
00:12:23.519Um I think it it just gives you another uh factor that is potentially in favor of doing chondroitinase rather than uh surgery.
00:12:23.519 -->
00:12:41.440Uh you know, when we're when we're having the conversation with the owner around the um the options for treatment, uh, you know, they they basically they fall between conservative, pure conservative management, traditional surgical decompression with or without fenestrations, or chondroitinase injections.
00:12:41.440 -->
00:12:58.080And you know, I think this um paper just basically adds a little bit of of uh of a pro, if you like, to um the the the um chondroinase option because it it is you know it's pretty easy to inject four discs.
00:12:58.080 -->
00:13:02.960Uh, you know, it doesn't take much longer to inject four discs than it does to inject one, in fact.
00:13:02.960 -->
00:13:06.799Um and and we potentially we could inject more than four.
00:13:06.799 -->
00:13:20.320Um so it it's potentially a big benefit, you know, if if chondroitenase is as good as surgery, which we don't know yet, but you know, the results are pretty good that we're we're finding.
00:13:20.320 -->
00:13:33.360Uh if it is, then the ability to target multiple discs, um, if that does genuinely reduce the risk of recurrence, that's a that's a big plus point for chondroitinase, alongside the other plus points.
00:13:33.759 -->
00:13:35.840I would guess that one of the plus points is money.
00:13:35.840 -->
00:13:38.320So we have at least two institutions.
00:13:38.320 -->
00:13:41.360How does, you know, uh on a factor, right?
00:13:41.360 -->
00:13:45.759Everybody has a little bit different cost, but is it three times more expensive for surgery?
00:13:45.759 -->
00:13:48.320Uh how does that conversation play out?
00:13:48.799 -->
00:13:50.879With us, that's almost exactly what it is.
00:13:50.879 -->
00:14:08.480Um we're we're offering it now as a as a treatment with uh an MRI under general anesthetic, um, unlike the the original sort of trial conditions where we were injecting based on the neuroosam alone, but we're we're able now to offer it with a with a sort of limited MRI just to confirm the diagnosis.
00:14:08.480 -->
00:14:19.039Um and we're uh we're charging that out at approximately one-third the sort of minimum cost of uh traditional MRI and surgery, yeah.
00:14:19.360 -->
00:14:29.679Yeah, at A ⁇ M it's a lot less because we're just targeting the disk based on physical and neuroexam alone, it's about a sixth of the cost.
00:14:29.679 -->
00:14:32.799Well, it depends on the breed because it varies with breed.
00:14:32.799 -->
00:14:49.200But one of the one of the things about the cost here is that so far we've had the enzyme supplied to us free of charge, and so we uh that doesn't come into the cost, and if we have to start charging for that, then it will put the cost up a bit.
00:14:49.840 -->
00:14:50.159Yeah.
00:14:50.480 -->
00:14:51.519That's a lot.
00:14:51.519 -->
00:14:55.919That's something for spectrum of care and access to care and all of those things, isn't it?
00:14:56.080 -->
00:14:56.240Yeah.
00:14:56.240 -->
00:14:57.679Yeah, absolutely.
00:14:57.679 -->
00:15:11.120It it's one of those things about how many more people have been able to come and have their dogs treated since we you know you become aware of how big this problem is and how it's that a lot of people are.
00:15:11.120 -->
00:15:19.440It it's really opens opened my eyes to a lot of the um access that people can't get.
00:15:19.440 -->
00:15:19.759Yeah.
00:15:20.000 -->
00:15:22.399Yeah, it's really it it that that's huge, actually.
00:15:22.399 -->
00:15:27.360Uh like I said, the the demand, the ongoing demand here in the UK is is incredible.
00:15:27.360 -->
00:15:34.639Uh, and you know, I get desperate emails from people on a daily basis, literally a daily basis, uh, usually more than one.
00:15:34.639 -->
00:15:48.639I've had a three or four today, for instance, and that's just a normal day, you know, and they're they're they're all generally people that have been quoted a price for MRI and surgery and and you know just haven't been able to afford it.
00:15:48.639 -->
00:15:53.600So, like Nick says, the the the ability to offer something that's much more affordable.
00:15:53.600 -->
00:16:04.159And and we're we're still doing the non-MRI version as well, which as Nick said is well in Cambridge it's it's even less than a sixth, I think, of the surgical price, you know.
00:16:04.159 -->
00:16:10.240So that's really uh uh and and and we think, you know, we think that that's a reasonable thing to do, don't we?
00:16:10.240 -->
00:16:22.480I mean, you know, it's the it the results from uh targeting the injections based on the neuro exam rather than on MRI don't seem to be any different than the ones that are having MRI.
00:16:22.480 -->
00:16:31.200Um so uh we think it's a reasonable thing to do, and and you know, it it's a really that is a super low-cost way of treating this disease.
00:16:31.519 -->
00:16:33.440Oh, that's amazing information for our listeners.
00:16:33.440 -->
00:16:34.799Thank you for sharing.
00:16:34.799 -->
00:16:44.000Now, looking to the future, Paul, what are the next steps for research on chondroitinase and what questions still need to be answered before this approach becomes more widely adopted?
00:16:44.320 -->
00:16:46.720Well, the prophylaxis is a big thing, I think.
00:16:46.720 -->
00:17:07.519Um, and uh one of the things I've actually been working on in the last uh week or so is trying to get um recognition by our governing body in the UK, the Royal College of Veterinary Surgeons, um, for using it prophylactically as a what they they define as an act of routine veterinary uh practice.
00:17:07.519 -->
00:17:18.880Um, because if they will basically uh add it to their list of routine veterinary practices, that means we can then uh sort of openly offer it to people uh for prophylactic reasons.
00:17:18.880 -->
00:17:26.880Um uh a lot of people are contacting me already and and asking if they can come and have their healthy dog injected.
00:17:26.880 -->
00:17:37.680Um, and I'm always saying no right now, um, partly because I haven't got time to do all those healthy dogs, but uh also because we haven't got that RVP um approval yet.
00:17:37.680 -->
00:17:50.880But I think, you know, I think we we both, Nick and I both think that that's probably the, if you like, the biggest market for it in the future um actually is is is potentially treating uh you know younger dogs prophylactically.
00:17:50.880 -->
00:17:57.839But I think the other things that you know we there are many questions that we still don't know the answer to, like long-term follow-up.
00:17:57.839 -->
00:18:03.759You know, we we're we're getting we're getting out three years out now from the the dogs that we started treating.
00:18:03.759 -->
00:18:06.079So we're getting reasonably long-term follow-up.
00:18:06.079 -->
00:18:11.519But you know, four, five, six years down the line, what what are the disks going to be looking like?
00:18:11.519 -->
00:18:14.559Um I think that's that's gonna be important.
00:18:14.559 -->
00:18:17.680How many disks is it actually reasonable to do in one go?
00:18:17.680 -->
00:18:25.519You know, if we if we decide to inject six or seven discs, is it would that cause a problem as opposed to to three or four?
00:18:25.519 -->
00:18:29.200Um those those kind of things would be really nice to know.
00:18:29.200 -->
00:18:35.279What are the disks look like when we image them after they've been um uh injected?
00:18:35.279 -->
00:18:40.400Um you know, could we could we get any samples of disc material afterwards?
00:18:40.400 -->
00:18:51.599Could we could we have some cases where we inject them following an MRI and then we follow up with MRI and see actually what happens to the disc and the extruded disc material?
00:18:51.599 -->
00:19:01.039I think those are you know really interesting topics to to think about, not not necessarily the easiest things to answer, but um yeah.
00:19:01.359 -->
00:19:03.599Yeah, a lot of great studies coming up.
00:19:03.599 -->
00:19:09.839Uh we have usually have one final takeaway and ask one person, but we have time, so I'd love to hear this from each of you.
00:19:09.839 -->
00:19:18.319If you'd like to share one key message with our listeners, we are mostly veterinarians, what would the takeaway be for you to share with them?
00:19:18.319 -->
00:19:19.680Let's start with William.
00:19:20.079 -->
00:19:30.160Yeah, I I would say that, you know, obviously we we need more studies and more prospective studies, but I I think right now it it should be viewed as an alternative to surgery.
00:19:30.160 -->
00:19:37.440And so, like like Paul said earlier, I think it's just another tool in our toolbox that we can use to treat this very common issue.
00:19:37.920 -->
00:19:38.640Very cool.
00:19:38.640 -->
00:19:40.160How about you, Nick?
00:19:41.200 -->
00:20:04.880Uh yeah, I mean I I think it's telling us something about spinal wood injury in dogs as well, that um that a lot of dogs don't need surgical decompression, and uh I think that that lesson is quite important um to uh get out to people so that they don't so that owners don't euthanize their dogs when they can't afford surgery.
00:20:04.880 -->
00:20:07.759That's probably one of the things I'd like people to know about.
00:20:08.000 -->
00:20:10.000It's always hardest to be last, Paul.
00:20:10.000 -->
00:20:13.599We got the other takeaways, anything different to add?
00:20:14.160 -->
00:20:14.720Not really.
00:20:14.720 -->
00:20:16.319I I I echo what Nick says.
00:20:16.319 -->
00:20:28.960I I think you know, one of the one of the things that we've really tried to sort of press home to to our colleagues is you know that there are that dog, most of these dogs do recover without surgery.
00:20:28.960 -->
00:20:38.960Um and uh, you know, when when surgery is not an option, uh not to to give up on them and and to offer owners uh other options.
00:20:38.960 -->
00:20:46.720You know, if chondroitinase is not available, then you know, offer them conservative management and and uh and support them through that.
00:20:46.720 -->
00:20:51.920Um and I think that's that's probably the the major take home.
00:20:51.920 -->
00:21:05.279Uh, you know, I think all this work is just kind of adding to that sort of body of evidence that we're we we've sort of been building over the last few years that surgery is not necessary in in many of these dogs anyway.
00:21:05.920 -->
00:21:07.839I'll ask a pretty naive question then.
00:21:07.839 -->
00:21:12.000I'm an e-quine surgeon by by the full disclosure.
00:21:12.000 -->
00:21:13.440What about cats?
00:21:18.640 -->
00:21:23.759They do get discernation, but they tend to get different sorts of discernation.
00:21:23.759 -->
00:21:32.799Although to be fair, I we we're thinking I one of the things we're thinking about with the chondroitinase is to expand it into different sorts of discernation.
00:21:32.799 -->
00:21:33.039Yeah.
00:21:33.039 -->
00:21:47.920And so cats may be an appropriate target, but you'd need MRI because uh that there's a pretty strong differential in cats that's not discernation um for the same presenting signs.
00:21:47.920 -->
00:21:51.920And so uh you definitely need imaging cats.
00:21:52.480 -->
00:21:53.119Yeah.
00:21:53.119 -->
00:22:00.799No reason why it shouldn't be, but um yeah, like Nick says it's not uh it's not as straightforward.
00:22:00.799 -->
00:22:13.359Uh we we we rely on the fact that if someone presents us with a five-year-old Dachson that's acutely lost the use of its pelvic limbs and has back pain, you know, it's it's got a disc until proven otherwise.
00:22:13.599 -->
00:22:16.799Um that's not the case with cats, yeah.
00:22:16.799 -->
00:22:17.200Yeah.
00:22:17.200 -->
00:22:18.640Exactly.
00:22:18.640 -->
00:22:19.279Unfortunately.
00:22:19.279 -->
00:22:23.440I could put it back to you and say, what about horses?
00:22:23.440 -->
00:22:28.559Yeah, I don't think they very often get um disc herniations, is my understanding anyway.
00:22:28.799 -->
00:22:34.720No, but I think you know, with standing CT now, we're gonna learn a lot more, especially cervical, lower cervical.
00:22:34.720 -->
00:22:44.319I think we're gonna learn, we already are learning, we just don't know structure versus function a lot of times with what we're finding on these pet CTs and standing CTs and standing MRs.
00:22:44.319 -->
00:22:47.200So maybe that'll be the next episode.
00:22:47.440 -->
00:22:49.279Yeah, no explanation there.
00:22:51.119 -->
00:22:54.000Yeah, big target to aim at.
00:22:54.000 -->
00:22:54.799Yeah.
00:22:58.319 -->
00:22:59.039We have those.
00:22:59.039 -->
00:23:00.000That's okay.
00:23:00.240 -->
00:23:00.640Yeah.
00:23:01.440 -->
00:23:04.319William, Nick, and Paul, thank you so much for joining us today.
00:23:05.039 -->
00:23:05.440Thank you.
00:23:05.440 -->
00:23:06.319Thanks for having us.
00:23:06.319 -->
00:23:06.960Thank you.
00:23:07.519 -->
00:23:11.279For our listeners and viewers, you can read William, Nick, and Paul's article in Javma.
00:23:11.279 -->
00:23:13.200I'm Sarah Wright with Lisa Fortier.
00:23:13.200 -->
00:23:16.480Be sure to tune in next week for another episode of Veterinary Vertex.
00:23:16.480 -->
00:23:20.480And don't forget to leave us a rating and review on EPA Podcast or wherever you listen.
