A discussion with Dr. Sasha Rabchevsky on current advances in spinal cord injury research

Dr. Alexander (Sasha) Rabchevsky joins Dr. Michael Fehlings to discuss autonomic and cardiovascular control after spinal cord injury, promising neuromodulation results, and the future of SCI research 

Learning goals:

• Cover the importance of autonomic function and cardiovascular control after SCI
• Discuss the impact of neuromodulation in SCI
• Provide an overview of future research directions in SCI 

The opinions of our host and guests are their own; ISCoS does not endorse any individual viewpoints, given products or companies. 

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Contact us directly with any questions or comments at iscos@associationsltd.co.uk

Transcript

Welcome And Guest Introduction

SPEAKER_01 0:10

Hello, I'm uh Michael Phalings, uh professor of neurosurgery at the University of Toronto, and I'm the editor-in-chief of Spinal Cord, which is a signature journal of the International Spinal Cord Society, or ISCOS. And welcome to our uh a podcast uh series in which, in my role as editor-in-chief of spinal cord, kind of interview and have conversations with prominent people in the field, you know, to highlight their areas of work and to comment on areas that I think are of broader interest to the spinal cord injury uh community. And so by way of disclosure, I have to indicate that the gentleman that I'm interviewing right now is a very dear friend. And um he sent me a photograph recently of um the two of us uh socializing uh together, but I have huge admiration for Professor Alexander or Sasha Rabchewski. Just a few um uh words. He has a very extensive CV, which I'm not gonna uh uh um uh uh uh uh uh uh talk about too extensively, but um Professor Ripzewski is a um professor of physiology at the University of of Kentucky, and he's an inaugural faculty member of their um uh renowned spinal cord and brain injury uh research um institute. And it's really a remarkable center. I visited the center, and it's really kind of one of the leading centers um in the um you know in the in the in the field. Um you know, Professor Urpchevsky has uh you know trained with some of the uh you know leading figures in in the field. Uh you know, he worked with uh Paul Ryer at the University of Florida, neuroscience graduate uh um uh program, uh did a uh postdoc um at the University of uh Paris um with Mark uh uh Pyshensky, um has also done work um uh with uh Stephen Scheff at University of Kentucky, so very, very strong scientific uh lineage. And then in his own uh right uh uh uh Sasha um you know brings a number of strengths. He's an individual with lived experience with uh spinal cord injury, so he has very unique insights from that perspective and um has um had a number of areas of interest, but probably um I think one of the underlying areas is related to autonomic uh pathophysiology, but there are a number of other areas. And more recently, um uh uh uh Sasha is authoring um an e-blast, and probably many of you who are uh listening to this uh a podcast will have received these e-plasts, which I think are a very kind of helpful way to disseminate information. So, Sasha, welcome, welcome to our podcast. Did I miss anything in terms of your uh um your your your background?

Autonomic Dysreflexia And Cardiovascular Risk

SPEAKER_00 3:05

Uh well uh thank you very much, Michael, and and no, I think that that summed it up. I guess I'll give my own kind of background here as far as well, I guess, why I'm here, uh why we're discussing. Uh for those who don't know, I I was paralyzed in a motorcycle accident in 1985, so quite a while back. Uh I then, before going to graduate school at the University of Florida, became a uh biological technician at Uniformed Services University to get back into the real thing, and uh and that introduced me to research. So I applied to uh medical schools and graduate schools, and I ended up going to University of Florida in 1990. As you said, I went to do my postdoc in Paris, France in 1995 and then came back to Lexington in '97 because they had a spinal cord program here, which at the time was fledgling. Um we just opened up with the Kentucky Spinal Court Hydro Research Trust Fund, which takes speeding tickets and drug driving tickets and uses them as a kind of a tariff, if you will, for um spinal cord injury research and funding uh in our state. Um so that that kind of gives a little bit of a background. Um as far as my research. Uh, I don't know how much I want to go into that, but I have been, like you said, really invested a lot of my time and interest over the past 20 years into looking at autonomic dysfunction, and particularly autonomic dysriflexia. Um I can recall at a time, about the time when we met Michael, where very few people in the general population really understood uh what spinal cord injury uh meant with regard to cardiovascular dysfunction. It was kind of a kind of a uh a very misunderstood term. Still to this day, it's kind of controversial about what autonomic dysroplexia is as far as severity and triggering, but at the same time, it's brought awareness uh and new avenues of research, which is what I'm really excited about. Um, is that, you know, for a long time, myself included, because I have I had FES implants that allowed me to walk with electronic neuroprosthetics, is that this is re-energizing the the, in my opinion, the the uh the the um energy and desire to want to be in clinical trials because we're seeing results with functual electrical stimulation as well as now this bouncement uh stimulation paradigms. So that's kind of the research aspect. So right now, the e-blast um is really honestly, and Michael, you you've been on their podcast with Unite to Fight Paralysis and Matthew Roderick. That organization, when I first introduced them in 2017 in Miami, before the NASCAG was formed, North American Spinal Crunchy Consortium, I just was enamored with the entire organization and Matthew in particular, because they were asking questions as me as a scientist, trying to keep up with the Joneses all these years of the paralysis, had been wanting to voice my opinion and concerns that I found Matthew, who has a son with spinal cord injury, was just unabashed to ask these questions of all of our, so to speak, experts. And it really brought me to the lightning light that we're we are really in separate worlds. We have a preclinical field, and then we have your field, the clinical field. The two, as you know well know, Michael, very difficult to merge. And I I'm I'm really happy that what's happening right now, and this is where I'm I'm kind of aiming a lot of my focus right now, Michael, is that I don't we are underrepresented as far as our voice, period. In the United States and in one of North America and Canada, we have a lot of registries, but we do not, we are underrepresented. And that is part of my push right now, is to say, you know, we have a problem with physicians. You wrote this wonderful article recently, uh co-wrote, with with with stating that there's a special spinal injury specialist problem. We can't, we have fellowships yet, they're not being filled. So that then translates to me, both as a scientist and a patient. Well, wait a minute. I'm talking about my research career so far. What about my health career? I will tell you, Michael, that health care for spinal cord injured individuals has plummeted. Um, there's very few specialists, and on top of that, you have to go to specialists for neurologic for neurogenic bladder or bowel. It's a very, very spread out thing. So, what I'm trying to do with my platform, if you will, is to try to bring more awareness and more voices to the table. So that that I'll I'll stop it there and we can we can move on.

Spinal Cord Stimulation And Real-World Impact

SPEAKER_01 7:33

Well, that's there are a lot of uh you know really um important messages that you know really you know resonate with me. And one of the reasons that I you know agreed to take on the role as editor-in-chief of Spinal Court, it wasn't that I was bored and didn't have enough to do, but um you know, I really felt that uh Spinal Court is a very special journal. It published a number of important articles, but really had the potential uh to assist with unifying the field and bringing in, you know, a number you know, a number of people. And I think one of the things that you know makes you you know very special, like uh apart from the fact that you're an amazing researcher and you know you're extremely thoughtful, but um, you know, as a person with lived experience, you know, you bring very unique insights in into a lot of these uh a lot of these issues, and you know, you've highlighted a number of the points. So one is the fact that uh I would say that many uh um clinicians and researchers uh uh don't have enough awareness around the autonomic and the cardiovascular you know issues uh uh you know that individuals with a spinal cord uh uh uh injury struggle with, and that you know, these are very you know important issues. And uh you know, uh cardiovascular health is uh is hard to maintain for anybody as they're getting older and is even more challenging, you know, when someone has physical challenges. And so, you know, that I I think that's an you know that's an important point. And then you also you know mentioned the importance, I think, of uh uh you know uh linking the field and increasing kind of the awareness. And in fact, uh, you know, you you made reference to an article that I I was uh a co-author on. It was uh one one of my uh former um uh uh uh postdocs, actually an orthopedic uh uh surgeon in in the in the US. And um I'm interviewing him this uh Frida uh Friday um at an Asia podcast actually to try to advocate for um you know I I think an increased um awareness of the fact that there are shortages of physicians who are um interested in the field, um, you know, and uh you know and so on. So um I think that um you know one of the other areas though that I want to kind of plug in in you know um into into you a little bit is that you know given the fact that you know you're doing this e-blast, you're very connected, um where do you see some of the you know kind of exciting areas uh emerging from a translational research perspective in spinal cord injury?

SPEAKER_00 10:27

Well, I'm a bit biased, Michael, because back in 19 uh excuse me, 2002, I elected as an assistant professor in research academia to get these uh uh FES implants to allow me to walk. So a neuroprosthetic, if you will. Now, that there's been a lot of hype, was it's been faded out. FES is used, no, don't get me wrong, but it's not universally distributed, and it's not easy uh to use uh because there's a clinical because basically clinical trials still going on. Um having said that, I did a sabbatic with Audrey Krashikov several years ago up in Vancouver, can uh Canada, and I saw firsthand, and which is what the purpose of my uh visit was, was looking at this transcutaneous spinal cord stimulation paradigms as well as the epidural. And quite frankly, I was awestruck. Um just because as a scientist, I like to see things and and report them, and when you have uh unequivocal yes or no answers, it kind of opens up the floodgates to say, look at the realm of possibilities we could do. Having said that, Michael, it doesn't temper, it doesn't, I need to temper that to say that basic science is very important, and you and I have been doing this for quite some time, trying to balance the two. However, um there comes a time where, and particularly in my stage of my career, where I'm looking for something that's going to be able to be deliverable within my lifetime, if you will. And while I'm doing work with mitochondrial transplantation, stem cells, and all these other types of things that we've been doing for years, I don't see personally those being implemented within my lifetime. And so I'm trying now in my more aged years to kind of more redefine where we are in science. So the excitement that I'm having to get to your point is that the spinal cord stimulation paradigms right now is one is on one hand, is a lot of excitement. I guess, Michael, one thing that concerns me, again, with regarding to registries and things, where is all this information that people are getting put into them, whether it's electric uh transcutaneous regarding stimulation paradigms and and whatnot, for conformity, for being able to share data repositories. This is what kind of confuses me a little bit because we have very wonderful anecdotal stories, but there's not a quantitative yet measure of how much people are becoming independent, for instance, uh or not dependent. So I I guess if if I were to sum it up, it's an exciting time because it it again, going back to the standards which were of Albert O'Guile, Canadian, and you know, this was in the 80s that they showed that there is potential for regeneration. This is now actually questioning, not questioning, but certainly arguing that do we really necessarily need to have regeneration, or can we have an electrical stimulation that somehow rewires things and then we get things to work? And I think that's the difference, also, is that we never had a gold standard, Michael. We had methyl predicts, which is still controversial. We had no standard. I'm not suggesting this phytophengy stimulation is a standard, but it's a it's a it's a it's a landmark where you get movement, some even counting as volitional. How can we tap into that? How can we augment the circuitry? That's when maybe the stem cells, the mitochondria, all that, that may come in. And I think that's this is the first time, Michael, that I've seen grants come through where they're gonna do a compound XYZ, but they're gonna combine it with stimulation. Because why? Because you know that something's kind of like tweaking the system. How can we ramp it? So I think I don't want to go on much further because I don't, I could, by the way, is that spinal cord stimulation is a very exciting paradigm. But I also want to ask you something, Michael. One of the articles that I sent also to you recently was that there's studies now saying that time which is time is fine, which is what you've been purporting, that there's not really a quality of life difference after you give acute versus more more. And again, that's to me, Michael, I've always thought, well, if you're strangling somebody, the longer and harder you strangle them, the worse they're gonna be. It's kind of wind open.

Registries Data Gaps And Measuring Outcomes

SPEAKER_01 14:34

Yeah, I'll I'll comment, you know, I'll I'll comment on that. And you know, in fairness, you know, the article was published in in Spinal Cord, and it's a very good article. But that article in question, which um came from a European study called Skypo, was really looking at ultra-early versus early surgery. And so it wasn't sort of the role of early surgery, they were looking at 12 hours versus 24 hours. So it's a pretty fine timeline.

unknown 15:03

Right.

Time Is Spine And Care Pathways

SPEAKER_01 15:03

And we actually have, and that and I took this also as a personal challenge because you know I've been a personal advocate of time as fine and early intervention. I can say that um that early surgical intervention has a dramatic impact on quality of life in general, right? And you know, one of the things that I want to um you know emphasize, I think, is the importance that we um you know implement care pathways to allow the early and effective management of patients. And just um for your interest, in Canada, we're adopting a national standard to adopt timus spine across the entire country. In the province of Alberta now, it's a provincial mandate where um all individuals with an acute spinal cord injury, when when feasible, of course, uh, will have um surgical intervention within 24 hours. And so that's a big deal. And so we're trying to model what's going on with time of spine after stroke. And you know, we've seen huge advances in the way stroke is managed, and then really trying to look across a continuum because I mean early intervention is only going to get you so far, it'll help. But as uh you know, the I think is a consensus in the field that treatments are gonna be multifaceted, and we need to personalize the approach for everyone as well, right? It's not a cookie-cutter approach where you know one thing is going to be um you know working um for everyone. So I I think you know to come back with the neuromodulation, um, you know, I think that this is um a very exciting area. I think it's complementary to some of the other approaches, protective approaches and regenerative um approaches. But I think one of the things that we're you know we're learning that if we want to apply a regenerative approach, we need you, you know, you can it's sort of the substrate to get re repair and regeneration, but you need to activate it in some way, either with an active rehab program or maybe with you know with stimulation or you know, or or both. Well, you know, it's uh it's amazing, it's amazing speaking with you. I always try to you know keep these conversations, you know, we you and I could talk for hours, and we will. Um but um you know I um I I think I'll probably draw this um you know to a you know to a to a close. And um, you know, I want to thank you, uh Sasha, Professor Uh Revchevsky for joining me on this uh podcast. Um it's hosted by If you're thank you very much for having me, Michael.

SPEAKER_00 17:41

I appreciate it.

Closing Thoughts And Eblast Recommendation

SPEAKER_01 17:43

And I would encourage all of you to read Sasha's uh eblasts. They're extremely informative and they're very broad, you know, very broad uh uh reaching. And you know, Sasha's touched on a number of um key points, um, I think uh ranging from the importance of sharing data and establishing informed registries, um, the importance of cardiovascular control, autonomic function, the idea that you can um uh uh kind of rewire some of the circuits and pathways in the injured central nervous system through electrical stimulation. This might be augmentative to other types of um other types of um other types of uh uh therapies. And then also we also touched on you know the importance of um you know recruiting and retaining uh uh specialists and physicians and healthcare practitioners in the area of spinal cord injury and that you know it's um you know it's important. And I think that um by uh you know highlighting the translational research, it's it's exciting. I know for like for young doctors, they want to get into areas that are cool, right? And I would say that you know we can kind of talk about the cool factor. And and the other thing as well that for me as a physician has been one of the most rewarding things is getting to know people and and uh like you. And you're such an amazing person. And uh Sasha, thank you so much for joining us.

SPEAKER_00 19:16

You're more than welcome, Michael. Thank you so much for having me, and uh I look forward to crossing paths again physically.

SPEAKER_01 19:22

Absolutely.