Clinical trials and research on spinal cord injury

Cathy: (0:00 - 1:58)

Hello, welcome to my lecture. 

Anne-Marie:

Welcome to SpineCare's 40 Voices for 40 Years podcast, a podcast about childhood-acquired spinal cord injury and dysfunction, produced by 2SER Radio on behalf of SpineCare Foundation. We'll have families join us to swap tips and share their experiences on plenty of topics. I'm the executive producer for this podcast series, Annemarie Reyes, at the community radio station 2SER 107.3 FM. This podcast is on research and clinical trials on spinal cord injury, and what's innovative in children's spinal cord injury were the hottest topics requested when we interviewed families. 

Joining today's episode of the 40 Years for 40 Voices podcast will be associate professor Catherine Gorey, an individual with a strong research interest in neuroscience, in particular traumatic brain and spinal cord injury. Cathy uses animal models in her work to investigate damage and repair to the central nervous system. Professor Mary Kalea also joins this podcast. She's one of Australia's most notable and accomplished neuroscientists. Mary is a professorial fellow in the Department of Medicine at the University of Melbourne, and is internationally recognized for her work in spinal cord injury and interventions in rehabilitation. Coming up are the two guests speaking to 2SER audio producer, Oscar Byrne.

Oscar: (2:00 - 2:14)

A very warm welcome to you, Mary. It's a true privilege to have you join us on the podcast. Just to start things off, can you just share a bit with the listeners at home, a little bit about yourself and your research to date thus far?

Mary: (2:15 - 3:05)

Thank you, Oscar. My name is Mary Kalea. I'm a professorial fellow in the Department of Medicine at the University of Melbourne. I started my career as a physiotherapist and have always worked in the area of neurological disability. I've worked with children and adults, and I left clinical practice to do a PhD in neuroscience quite a long time ago now. And I've done both animal studies and clinical studies that have been focused on really understanding how the brain and the nervous system control movement and how we can assist recovery of movement after a brain or spinal injury.

Oscar: (3:06 - 3:21)

That's quite the resume. Very impressive indeed. And look, you're about to embark on some pretty exciting research applying neuromodulation to the spinal cord. For the listener out there who isn't totally familiar with neuromodulation, what is it?

Mary: (3:21 - 6:28)

Well, neuromodulation means the alteration of nerve activity through the delivery of a particular stimulus. And there are many stimuli that can affect the nervous system. I mean, one is a drug. There are a number of drugs that change the nervous system. They alter spasticity or they alter consciousness. But typically, we use neuromodulation when we talk about electrical stimulation. And we've used electrical stimulation for many, many years in therapy to stimulate muscles or to stimulate sensory function. And now, the technology has improved to the point where we can now stimulate the spinal cord directly. And that's what my research is all about now.

Oscar:

Great, tell us a bit more about that research and SCIPA. 

Mary:

SCIPA was a program of research that I led quite a few years ago now. It was a series of four projects that were conducted across the whole of Australia, including all the spinal units in Australia and New Zealand. And those projects were focused on exercise after spinal cord injury, looking at the effects of intensive exercise and asking the question of whether intensive exercise could lead to neurological recovery. Overall, we found that exercise was really important and very beneficial. It didn't actually lead to people walking again or using their hands again if they were unable to use their hands.

Although people got stronger and fitter and their function improved, but it didn't lead to neurological recovery. So that meant that exercise is important, but insufficient for driving neurological recovery on its own. And that's where neuromodulation comes in because in recent years, there have been techniques developed for stimulating the spinal cord. The preliminary experiments have been with implanted stimulators. And those showed that when you stimulated the spinal cord in combination with exercise, you ended up getting some neurological recovery. 

Now they've developed transcutaneous stimulation. That is, it's not an implanted stimulator. It's applying stimulation through electrodes on the skin. So that's non-invasive. It doesn't involve any surgery. The electrical impulse can get through to the spinal cord and stimulate the spinal cord directly. And that's what we're going to use in people with tetraplegia, that is those who have injured their spinal cord in the neck region and who have difficulty using their hands. And we're going to apply this stimulation plus intensive rehabilitation to see if we can drive neurological recovery and improve hand function as a result.

Oscar: (6:29 - 6:41)

What are some of the key messages from that research you want to share when it comes to, I guess, giving advice on keeping children healthy and well and ready for advancements in science?

Mary: (6:42 - 9:34)

Well, the most important thing to remember is that there's the principle of use it or lose it. So if you don't use a part of your body, it will deteriorate in some way. So if we sit all day and not stand up, our muscles can get weaker and that's not a good thing. And of course, in someone with spinal cord injury who has to sit because they can't stand up by themselves, that means that there's a deterioration of the muscles and the bones below the level of the injury through disuse. It's not the child's fault or the person's fault, but it's just what happens after a spinal cord injury. And it's not only the muscles and the bones, but the nervous system too can deteriorate below the level of the injury.

And so it's important that we promote the health of those parts of the body through some form of exercise because exercise is really good for the muscles and the bones, the circulation, and as we know, the peripheral nerves as well. So we need to keep those structures healthy because in the event of people finding a cure for spinal cord injury, we actually need the peripheral nerves and the muscles and the bones to be fit enough to be able to take advantage of that recovery. So how do we keep those areas below the nervous system healthy?

Well, exercise is really important. I mean, even just physical activity, just getting about and activating whatever part of the body that you can use is actually really good for you because it stimulates your heart and lungs, important for your brain health, important for your social health and all of that. But in the parts below the level of the injury, often we need some help to exercise those parts. And so now we have electrical stimulation, which can be used in the form of cycling or just neuromuscular stimulation to just keep the muscles from deteriorating. And the pull of the muscles on the bones can actually help the bones as well. It's not perfect, but it helps.

And obviously that sort of activation of the muscles also keeps the circulation going and the peripheral nerves which drive the muscle going. So that's one way of keeping the nervous system healthy. What that means is that it doesn't actually mean that you'll suddenly be able to move your limbs because we know that that sort of intensive therapy, unless you have a very incomplete injury, that's not going to be possible at the moment. But nevertheless, it will actually keep the system healthy enough so that you can take advantage of future developments. I think that's a very important message.

Oscar: (9:34 - 9:52)

Definitely. Often we hear there's not enough clinical trials being done in kids with spinal cord injuries and innovative products are often just made in adult sizes. How important is the consumer voice when it comes to real change and what can families do with that voice?

Mary: (9:52 - 13:00)

Well, the consumers are very important because they can actually put these issues before the decision makers. In terms of research, there's really not been a lot of research in children with spinal cord injury. Probably because the problem itself, even though it's obviously really important to the people that are involved, in the grand scheme of things, when you think about public health, it's issues like diabetes and stroke and things that affect a large number of people that are going to get the research funding because obviously they cost the government a lot of money.

But it's important that the issues being dealt with by people with spinal cord injury and their families are put before decision makers because then they can make decisions about funding. Obviously, with NDIS, that's been a very important thing. People with disability have been able to make a big impact there in getting this scheme going. We also need more research because that's the only way we're going to find things out, find out what works and how it works. And we need lobbying really by the consumers to put these issues before the decision makers. Because researchers on their own, while they might have a great interest in a particular area, unless they have research funding, then research is very difficult to do because it's very time intensive and you need personnel to be able to do it.

The other thing is, I guess, in terms of equipment, is that there has been equipment that has been found useful in adults with spinal cord injury. And in those cases, I think it's important for the consumers to lobby the companies to start making things in child sizes. While the companies might not make a lot of profit on that because the market, I guess, is a lot smaller than in the adult population, I think those companies should be able to see it as a public service and try and help out.

Oscar:

And just finally, Mary, why is the research process so important? 

Mary:

Well, research is the only way we can find things out. I mean, that's why I went into research because as a clinician, there were a lot of questions I had. I wanted to know, for example, was I making a difference? How did I make a difference? And it was only by doing research that I could find things out. For example, I learned a lot more about how the nervous system works and about neuroplasticity and the things that drive it. So we have to keep doing research because that's the only way we can refine what we do. I mean, in the past, treatments for spinal cord injury were of a certain type.

And now, because we have more knowledge, we know that we can add more to the rehabilitation process, like, for example, FES cycling, activity-based training, neuromodulation, all of these things have come about through research that will continue.

Oscar: (13:01 - 22:30)

On that note, Mary, I've got to say a big thanks for joining us on the podcast. It's all been very insightful. Really appreciate it.

Joining me on the podcast is Associate Professor Cathy Gorry. Welcome to the show. Just to start things off, Cathy, you want to tell us a bit about you and your role in the spine, I guess, spinal care world.

Cathy:

So I'm the head of the Neural Injury Research Unit at UTS. I've been studying spinal cord injury for over 10 years now, but more and more I'm focusing on pediatric spinal cord injury and how spinal cord injury affects young children and young animals. 

Oscar: 

Great, and Cathy, as one of the few researchers in the world exploring infant animal models of spinal cord injuries, can you maybe shed light a bit on some of the insights into the differences, some of the key differences between adults and children in that area?

Cathy:

So what we know is children are not just scaled-down adults. They've got very different anatomical and physiological differences that will affect the severity and the extent of a spinal cord injury. They also have real differences in the causes of spinal cord injury, and we don't know a lot about how they respond to that injury. It's an area that hasn't had a lot of research in it, and so the first thing we need to do is establish what those differences are. Some of my earlier research has shown that there are differences in the way that the injury manifests, and we're thinking that there'll also be differences in the way that children recover from spinal cord injury. 

Oscar:

Okay, and you mentioned that there isn't a lot of research in that field. Why is that? 

Cathy:

So it's very difficult to examine very young tissue for obvious reasons. Nobody wants to investigate children and perhaps make an injury worse, or there's differences in different age children as well, so we don't know the full extent of the patterns of injury across those ages.

Oscar: 

Right. Will that hopefully change over the next few years? Can you see more time and money being put into that area?

Cathy:

Yeah, I think the more we understand about childhood spinal cord injury, the better we can respond to that. One of the things we do know about children's spinal cord injury is the cause of injury is quite different between children and adults, so adults tend to have about 80% of cause from traumatic spinal cord injury, typically from a motor vehicle accident or a sporting injury. Children, on the other hand, have a completely different injury. It's what we call often non-traumatic, so it might be caused by compression of the spinal cord due to something like a tumour. So if we can understand what that injury is, we'll be able to see if we can come up with strategies to repair that type of injury. 

Oscar:

A big part of your job revolves around experimenting with animals. Maybe delve into that a bit. What does that entail? Maybe explain, why are animals used?

Cathy:

Again, before we can even contemplate trialling medical interventions in children, we need to make sure that they're going to be safe and they're going to be effective, so we do tend to use animal models, especially with a complex condition like a spinal cord injury, which has got a lot of different facets to it. So we have very stringent animal ethics approval to undertake these studies, but we use young animals, rodent studies, to try and examine what's happening at the tissue level or at the spinal cord level so that we can then develop interventions that could be used for children. 

It would be very difficult to undertake a clinical trial on very young children. Of course we don't want to make an injury worse with our intervention. We don't want to have an invasive surgical intervention any more than is absolutely necessary. So we tend to do these things in animals first just to make sure that everything is safe, effective, and we can trial techniques or interventions early. 

Oscar: 

With the suggestion that children may have better recovery than adults from spinal cord injuries and certainly different patterns of inflammation, what are the next steps and what are you hoping to see? 

Cathy:

So I think we and others have established that very young children or very young animals tend to have a better and faster recovery than their adult counterparts. Some of the work that's been done has indicated that there's less inflammatory response in very young animals compared to adults. So what we're hoping to do is probably a twofold approach to utilise that reduced inflammatory environment which is thought to be beneficial, but also there are a type of stem cell which are located within the spinal cord. So these are called endogenous. And because they're stem cell-like, they can grow into new nerve cells or new support cells for nerves. 

So we hope to eventually harness those properties of these stem cells to grow into new nerve cells or into support cells to encourage nerve cell regeneration. And we hope to encourage these cells to repair the spinal cord. And because we're doing this in very young animals, their central nervous system isn't completely developed. So we're hoping that it's much more plastic, it's much more amenable to these sorts of interventions. And that's where we hope to go with this research eventually is to come up with a way to stimulate those stem cells inside the spinal cord to regenerate or repair the spinal cord tissue itself.

Oscar:

And you mentioned there, of course, the endogenous stem cells and their applications to neonatal animals. Can you maybe get into a bit more, what are the learnings so far and what this might mean for the future of young humans? 

Cathy:

At the moment, when a child has a spinal cord injury, there might be surgical interventions to maybe decompress the spinal cord injury by removing a tumor or straightening the spinal column, but very little is actually done to the spinal cord injury itself. So what we hope to do is develop a way that we can try and address that spinal cord injury damage, perhaps sometime after the actual injury and after the surgical intervention for the injury. And we don't know what those timings look like. So this is something we'll be doing in the future is trying to work out if we can decompress the spinal cord quite early, maybe months or years down the track will be a more suitable time to actually try and address the spinal cord injury and try and get functional recovery.

So it's all a learning curve. We don't expect this to be a single intervention. It's probably going to be a combination of work that I'm doing and work that other people are doing. I can imagine it's not gonna be a very straightforward single track cure for something like a spinal cord injury. It's a very complex injury. It has different elements depending on the cause of the injury. Of course, the age of the child will be a big factor, especially with very young children. So there's a lot of unknowns, but we think that the central nervous environment in early animals has a much more potential to be manipulated. And then we hope that whatever we actually find in children, we can somehow then implement an adult spinal cord injury as well. So we can try and recreate that infant-like environment. 

Oscar:

Well, that's all really exciting research and hopefully over the next few years, how long do you think, I mean, you probably can't put a number of years, but what's the timeline for something like that if you could even put a number on it?

Cathy: 

Look, this sort of research goes very slowly. It takes a long time to implement. We're probably looking at the animal studies going for at least five or more years. And then before we can even consider how that might be translated into a clinical scenario. Y

Oscar: 

Yeah, and for yourself personally, what keeps you motivated and what is your passion for this area come from? 

Cathy:

Look, I've spoken to people who are living with a spinal cord injury and the overwhelming sense I get is even if we can improve function, even a small bit, it will make such a difference to their lives and their quality of life.

Oscar:

Beautiful, I think that's the perfect way to end off the podcast and a really important note and message.

Ann-Marie (22:31 - 23:30)

And you just heard our two guests, Professor Mary Galea from the University of Melbourne and Cathy Gorry from the UTS Centre for Health Technologies - speaking to radio 2SER-FM's Oscar Byrne, and ending that interview. You've been listening to SpineCare, 40 Voices for 40 Years, produced by radio 2SER-FM. You can subscribe wherever you get your podcasts. This series is recorded in Sydney. We acknowledge the Gadigal people of the Eora Nation as the traditional owners and ongoing custodians of the land where we record this podcast. We extend our respect to the traditional owners of the lands that you and our guests join us from. I'm executive producer Anne-Marie Reyes. See you in the next podcast. ♪♪♪