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March 19, 2019 – Dr. Kelly Diehl talks about spinal cord injuries and diseases among cats and dogs with Dr. Natasha Olby, Professor of Neurology and Neurosurgery at North Carolina State University. Dr. Olby discusses her Morris Animal Foundation-funded work to find treatments and optimize recovery for these issues.

00:18 Dr. Kelly Diehl: Welcome to Fresh Scoop, Episode Six, Spinal Cord Diseases in Dogs and Cats. I'm your host, Dr. Kelly Diehl, Morris Animal Foundation's Interim Vice President of Scientific Programs. And today, we'll talk to Dr. Natasha Olby, Professor of Neurology and Neurosurgery at North Carolina State University and a long-time Morris Animal Foundation-funded researcher. For those of you who may be new to Fresh Scoop, this is the monthly podcast of Morris Animal Foundation, the largest non-profit foundation in the world dedicated to funding studies that find solutions to serious health threats in animals. Founded in 1948, by Dr. Mark Morris Sr., a veterinarian, we've invested more than $126 million in more than 2600 studies that have improved and protected the health of companion animals like cats, dogs and horses, as well as wildlife.

01:13 DD: In each episode, we feature one of the researchers we fund or one of our staff members, discussing their work in advancing animal health. Whether you're a practicing veterinarian, technician or student, or just an animal-loving science geek, Fresh Scoop is the podcast for you. You can learn more about us at morrisanimalfoundation.org. Okay, on to today's show. Today, we welcome Dr. Natasha Olby, Professor of Neurology and Neurosurgery at North Carolina State University. Dr. Olby earned both her veterinary degree and PhD from Cambridge University. She did her neurology residency at North Carolina State University, and then became board certified before joining the university's faculty. She was the American College of Veterinary Internal Medicine Neurology president from 2008 to 2011, and in 2017, she was awarded the honor of the Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair of Gerontology.

02:19 DD: Dr. Olby has earned a few grants from Morris Animal Foundation, but today we're going to focus on her work with spinal cord issues in dogs and cats, though the focus will primarily be on dogs. So welcome, Natasha, it's great to have you here and thanks for joining us.

02:38 Dr. Natasha Olby: Thank you very much for that introduction. It's great to be here.

02:42 DD: Before we start into a little bit more on your projects, can you tell our listeners a little bit about your background as it relates to your research?

02:56 DO: Yes, absolutely. Well, as you can tell, and as you noted in the introduction, I am actually English, and I grew up in northern rural England, in James Herriot land in fact, in Yorkshire. And so I went to vet school really wanting to be a mixed practice veterinarian with a big focus on farm animals to be honest, but rapidly changed course as I learned more about small animal medicine. And early on decided I wanted to try to advance what we knew about medicine and veterinary medicine and our care of animals and became fascinated with neurology.

03:38 DO: I joined a lab, I was in practice for a brief period, which I enjoyed thoroughly, actually, but then I went back to Cambridge and joined a lab that was focused on multiple sclerosis research. But I was this little outpost at the lab that was investigating spinal cord injury and how the spinal cord responds to injury, and in particular, how the supporting cells of the spinal cord respond to injury. And so I completed a PhD and a postdoc there, but decided I really wanted to have more of a clinical focus, and at that point, moved across to North Carolina to do a residency.

04:15 DD: And you were talking about this early experience in research with spinal cord disease. Why have you then... You alluded to it, but why did you decide to really focus a lot of your research on the spinal cord in particular?

04:32 DO: Honestly, the initial decision was really that this was a lab I wanted to join and they happened to be doing a lot of work on spinal cord disease. So that was the initial motivation. But once I got into it, I became very fascinated with how the spinal cord, first of all, responds seemingly... It's a little bit difficult to understand why some injuries are very severe and others are not. So that aspect of spinal cord injury interested me, but then this possibility that you really could, potentially, improve outcome from spinal cord injury kind of got me hooked. And part of the rationale for that is it's such a common problem in veterinary medicine. We see so many animals with spinal cord injuries that are otherwise healthy, and so if we could influence their outcome, we could really have a big impact.

05:29 DD: Okay. And you were just talking about this, but what are some of the most common spinal cord diseases you see in the clinic in dogs and cats?

05:43 DO: Well, overwhelmingly, we see dogs with spinal cord injuries. And the most common injury is a very sudden, or what we would call an acute injury because an intervertebral disk, that nice cushion that sits between vertebrae, that intervertebral disk degenerates and typically in our dogs, will explosively herniate, we call it. So that it compresses the spinal cord and causes an injury.

06:11 DD: And why do you think dogs get... We see that in dogs more than cats? Is it anatomy or the type of injuries?

06:21 DO: It's genetic, I would say. So we see these explosive disk herniations in particular breeds of dog, most commonly. I think everybody's familiar with the Dachshund breed, but any little, short, bow-legged breed is really predisposed to it, as well as some other breeds. And so, genetics has a lot to do with it, and in fact, we actually understand now quite a lot about the genetics from some work that's been done in California. But the mutation that these animals carry, these dogs carry, causes really early degeneration of the disk and makes it much more susceptible to this explosion, if you like.

07:05 DD: So Natasha, tell us about the breeds of dog that are most commonly affected by herniated disk problems.

07:15 DO: Okay. So, if we're talking about these very sudden explosions of the disk, what we call an acute disk extrusion, the most affected breeds are all the short, bendy-legged breeds, we also call those chondrodysplastic breeds. And the poster child for that is the Dachshund, so they are affected, by far, more commonly than any other breed. But then we also see Lhasa Apsos, Pekingese, Bichon Frise, we see Cocker Spaniels, so those are dogs with straighter and longer legs, we do see them being predisposed. We see Beagles, we see French Bulldogs, to name a few. All of these dogs will come through our service really regularly. We then also see other breeds of dog that are larger just occasionally have this problem. So, we certainly do surgery on Labrador Retrievers and Dobermans and a variety of those middle-sized breeds. They're less commonly infected, but I think it's important to realize that any breed of dog could be affected with this problem.

08:28 DD: In the context of what you're seeing in your neurology practice, realizing you're in a veterinary teaching hospital, where do you think spinal cord diseases in dogs lie in terms of frequency and impact on pets and their owners?

08:47 DO: We find the frequency questions a little bit difficult to answer because we all live in our own skewed worlds. Approximately half of the cases that we see on neurology are spinal cord injury cases, and they are pretty devastating to the dog and owner, to be honest. Because these problems cause paralysis, so the animal is unable or has reduced ability to move around. They're quite often painful, so you have a pet that's in pain. And then one of the most difficult things is, quite often, the patients can't urinate, and so if you are unable to urinate on your own, you have to have an owner who can express your bladder, for example, which really increases the difficulty of just nursing care and management. So if you have a spinal cord injury, it has a pretty significant impact on both the pet and the pet's owner.

09:56 DD: Just briefly, because this will merge into what I want to talk about as far as your grants with Morris Animal Foundation. Tell us a little bit about how spinal cord disease is typically treated in dogs, sort of the conventional therapies we have available.

10:15 DO: Yes, absolutely. When we're diagnosing spinal cord disease, we almost always end up doing an MRI or perhaps a CT scan, and what we're looking for is compression of the spinal cord, be it due to a disk, or due to a cancer, or a fracture. So in general, if you have something that is compressing the spinal cord, we try to surgically decompress it. Then the treatment depends a bit on what that underlying cause is. So for example, if it's a cancer, then maybe they're going to get radiation or chemotherapy, for example. If it's an infection, we see infections in the bones of the spine, so we might treat with antibiotics. We can see inflammatory diseases where the dog is producing an abnormal immune response against its own nervous system, and those we treat with immunosuppression. So it depends a little bit what the underlying disease is.

11:19 DO: However, the most common cause of spinal cord disease is something related to a disk, whether it's that acute blowout disk that I talked about or something that's happening a bit more slowly. And so, our focus with that is always, first of all, surgically decompress, and then support and rehabilitate the patient and give them time to recover. To a large extent, if the spinal cord still has some connections going across the area where the injury happened, the animal has the ability to recover with appropriate supportive care and rehabilitation.

11:58 DD: That's really helpful and a good lead-in. And I'm going to put you on the spot a little bit, and I would like you to tell us about your Morris Animal Foundation-funded research. And I know you've had a lot of grants, so congratulations, that's something to be pleased about. Can you tell us a little bit about what you were looking at in a few select grants and what you were... What it involved as far as the actual study?

12:29 DO: Yes, absolutely. And yes, I'm very grateful to the Morris Animal Foundation. They've supported a lot of work. I think the easiest way to summarize it is, I have done spinal cord injury studies in dogs with a naturally occurring disease, so dogs coming into our clinic in two different areas. So one is in those dogs that had a spinal cord injury that was extremely severe and damaged their spinal cord so much that they remained paralyzed. And then the other is in the management of these dogs that have come in with disk herniations, and they've had surgery, and we've looked carefully at how you can best optimize their recovery.

13:14 DO: So if we take, first of all, the chronically paralyzed dogs. These are dogs that may have been paralyzed for months or even years at the point they come into our studies, and they are often using a little cart to get around, and their owners are extremely good at expressing their bladder and caring for them, providing the appropriate nursing care that they need. And we've done two different things with them. Number one, we did quite an ambitious study, I would say, where we were looking at combining different types of cells that we'd harvested from the patient. So one was a stem cell that we got from fat and the other was a cell called a Schwann cell, so it's a cell that actually helps support your peripheral nerves, the nerves that come out to your muscles and it can support regeneration of nerves. So we took these patients, we did biopsies to get those tissues, we grew up the cells, and then we injected them back into the spinal cord injury. And the questions that we were asking is, number one, "Is it safe to do this?"

14:27 DO: And these were all dogs where the owners were incredibly dedicated to their care, of course, and also very dedicated to enhancing what we knew about all these strategies of treatment, and so they were willing to come back and come back for re-check so we could follow them up for a long time. And we were looking, number one, at the safety. Were there any problems at all associated with this? And we concluded that there were not, they tolerated it incredibly well. And number two, did we see it improve them at all? And we actually had a control group, all the dogs ended up getting the cells, but some of them got them later in the protocol, if you like, so that we could compare what happened. And we really did not see any convincing difference between them. We were hopeful at first that we were seeing some differences, but this was a blinded study, and when we ultimately looked at our data, we didn't see any difference. Now, I would say that was a little disappointing, but at the same token, these were dogs that had been paralyzed for a long, long time, so they were the most challenging patients to try to improve.

15:37 DO: The second study that we have done in these chronically paralyzed dogs is looking at a drug that will enhance the excitability of the nervous system and enhance conduction of nerves in the spinal cord. Well, it enhances conduction everywhere in the nervous system. But the rationale behind that is that we've had a very severe injury. However, even though no messages are getting across the injury, there are still some nerves there that are damaged but they're still anatomically there, they're still intact. And so the idea was that this drug would enhance their excitability. And we did a couple of different studies on this, and in one, they were completely paralyzed with no recovery at all and we found that this class of drug did improve them. And then we looked, and this was our Morris-funded study, we looked at dogs that had actually made a slight recovery from their injury, it just wasn't a very good recovery. And we found these drugs did not help that group of dogs.

16:45 DO: So a couple of different studies in these chronically paralyzed dogs. And we have yet to get the breakthrough in those, although we have taken from those studies the knowledge that the class of drug, it's a potassium channel blocker, we call it 4-aminopyridine, that it can help some dogs. So we have now incorporated that into our clinical practice and many rehab clinics now use that as well. So that's kind of one side of our work, and then the other side was just looking at strategies to support dogs and improve the speed and level of their recovery. So in these, we focused on dogs that probably were going to recover, had a good chance of recovery after surgery, but it takes time, so could we improve that? And so, the first of those studies was looking at whether we could decrease their risk of developing a urinary tract infection during that recovery phase.

17:46 DO: Why were we interested in that? Well, I've mentioned a couple of times that paralyzed dogs cannot urinate either, and these dogs that recover go through a period of time where their bladder is not working properly, and so they're at increased risk from urinary tract infections. And so we did a blinded study looking at whether, if we gave them cranberry extract, we could reduce their risk of getting an infection, and that study was really interesting. So we did not show an effect of the cranberry extract we were giving when we compared it with our placebo group, and we were completely blinded, we didn't know which group was getting the active drug and which was getting the placebo. But in that study, we also measured activity in the urine that cranberry extract will enhance, and it's an activity that helps block the bacteria, particularly E. Coli, from binding to the blood wall and getting that infection started. And we actually found that a lot of these dogs had this activity naturally, they had it anyway, and that activity was indeed associated with a decreased risk of these E. Coli infections.

19:03 DO: So that was a really interesting study and left a lot of questions, as many studies do. So, for example, should we be dosing the cranberry at a much higher dose, for example. So that was the first study. And then the second study was looking at early implementation of quite complicated, or should I say concentrated, staged rehabilitation. And the purpose of that study was to answer two questions, can we start intensive rehabilitation right after you've had surgery for a disk herniation? And the second was, can we increase the speed and level of recovery? And again, we compared this to a control group who just got very standard post-operative care, and we did a two-week treatment protocol in both groups. Again, we were blinded, we didn't know which group the dogs were placed in, they were randomly placed in the groups, and then we, the people who were assessing their outcome, didn't know which group they were in.

20:17 DO: And we found that it was very safe to start rehab pretty much on day two after the injury, but we found no difference in recovery in these two groups of dog. However, interestingly, we found that these dogs that had been hospitalized and cared for really intensively for two weeks, when compared to the dogs in our previous trial that got cranberry but otherwise were treated exactly the same way... However, they were released to their owners, they went home. We found that the dogs in our rehab trial actually recovered walking ability quicker than the dogs that went home. So we feel there is something important in that post-operative two-week period. We don't know if it's related to how strictly they were rested in the hospital or that we were there assessing them every day, so taking very close attention to their level of pain and whether they were developing any infections or any post-surgical problems, but certainly they... All dogs in that trial did well, whether or not they were getting intensive rehab.

21:32 DD: How are... You alluded to this, but how are people, or yourself, or your clinic, using what you've found in your studies and building on them, or where are you thinking of going next with some of the work and information you've already found out?

21:51 DO: Oh, there's all kinds of bits of information there, and I could talk for far too long, so I'll try to edit myself. With our chronically paralyzed dogs, we continued along the line of discovery, if you like, that we had made when we looked at our potassium channel antagonists. And we did a follow-up study looking in detail trying to figure out why some dogs responded extremely well to it and some did not, and we found it was all related to how excitable the local circuits that drive stepping, so their circuits that are embedded in the spinal cord, how excitable those circuits are. And so dogs in which the level of excitability of those circuits is high, those dogs are much more likely to develop stepping over time. And dogs where it's low, they are much less likely to. So we've started working on how we can enhance the excitability of those circuits, both with rehabilitation techniques and with drugs. In terms of our dogs that are making a more routine recovery after spinal cord injury and surgery, so these are dogs that we anticipate will recover, but we're just trying to enhance that we're looking again at our rehabilitation strategies.

23:20 DO: And we're just working on devising a new rehabilitation strategy for those dogs that perhaps focuses on some slightly different things. One of the things that happened, associated with these trials, is that whenever we have a dog in a trial, we collect very detailed information on how it's recovering every day. And we have found that that information has been an incredible resource for trying to look at predictors of outcome and things that might be a warning that things are not going well, for example, and we've actually had numerous publications come out of that now. Looking for complications like a terrible complication called myelomalacia, where the spinal cord suddenly degenerates. And so, I think it's important to note that these trials helped us to look at very specific questions, but in addition, all of the information we generate just enhances our knowledge and our ability to design trials to look at questions in a very focused way.

24:35 DD: So that makes me think, where... With what you're talking about you're going to be doing and the benefits of some of the data collection, it sounds like a happy unintended side bar for this. Where do you think people are going to be looking, yourself and others, over the next 10 years in spinal cord and spinal disease research?

25:02 DO: I think that people are going to be looking at a number of different frontiers, to be honest. So, the first is, can we get better markers of the severity of injury at the time that an injury happens? And so we have tried for a long time to predict outcome, and for most dogs, we can do that based on our exam of the dog and the severity of the signs, but dogs with very severe injuries can't feel their legs and can't move their legs. Some of those will make an excellent recovery and some won't recover at all. So I think people are really focusing on ways in which to pick out which dog is which from simple blood tests looking at biomarkers of injury. And that certainly is a frontier that is, I think, going to change a lot over the next five years, that we'll end up with bedside tests that can really help us with that.

26:02 DO: New surgical techniques are being developed all the time to try and make more efficient surgeries that are less expensive and have less impact on the patient, negative impact on the patient. In terms of recovery from injury, there is enormous focus on rehabilitation in these dogs with very severe injuries, not the dogs with milder injuries. So I think we'll see a lot of new rehabilitation techniques and protocols come out. I think we need to do a lot better than we are doing at the moment. And then there are areas like transplantation of stem cells, a lot of different groups across the world have been working on that and there are so many different options of types of cells and timing of injection of cells, that I would say the field is still a bit confusing, but I'll be interested to watch and see if something comes out of that in the future.

26:58 DD: That sounds really exciting. I can't wait to hear more. I think that's going to be a frontier for us. So Natasha, thanks for being with us today. That was super informative, I really appreciate it. And we hope we get a chance to talk to you again.

27:14 DO: Well, thank you very much. I really enjoyed that. And thank you again for all the support over the years.

27:20 DD: Oh, no worries, so you take care and we'll chat soon. And good luck with all your research.

27:25 DO: Alright, thank you. Bye-bye.

27:27 DD: Bye Natasha. That does it for this episode of Fresh Scoop. Once again, thanks to Dr. Natasha Olby of North Carolina State University for joining us and talking about spinal cord issues in dogs. We'll be back with another episode next month that we hope you'll find just as informative. The science of animal health is ever changing, and veterinarians need cutting-edge research information to give their patients the best possible care. And that's why we're here. You can find us on iTunesSpotifyGoogle Play Music, and Stitcher. To learn more about Morris Animal Foundation's work, please visit us at morrisanimalfoundation.org. There, you'll see how we bridge science and resources to advance the health of animals. You can also follow us on FacebookTwitter, and Instagram. I'm Kelly Diehl, and we'll talk soon.