Pathogenesis of Diabetic Peripheral Neuropathy with Corlius Birkill – Talk Neuro to Me Podcast

"Welcome to "Talk Neuro to Me," the podcast where we dive deep into the intricate workings of the nervous system. In today's episode, we're joined by Corlius Birkill to unravel the complexities of diabetic peripheral neuropathy. Join us as we explore the pathogenesis behind this condition and shed light on its neurological implications."
 

Transcript

Dr. Freddys Garcia: [00:00:00] Pathogenesis of diabetic peripheral neuropathy a new perspective.

Hello and welcome to talk neuro to Me. My name is Dr. Freddys Garcia. Today I’m joined by Corlius Birkill. Corlius, how you doing, my man?

Corlius Birkill: Great. Thanks. Dr. Garcia How are you?

Dr. Freddys Garcia: I’m excited to spend some time with you because we have some things to talk about. You guys have some published literature, but before we dive into that conversation I have a bio on you so I could share with everybody about how awesome and brilliant you are.

So if I could talk about you for a moment here, Corlius Birkill is founder and CEO and head of research of Algiamed Technologies. He has 26 years experience in research and development, project management, and component level design of electronic medical devices. He excels in research, characterization, process modeling, and integration for developing new electronic medical devices.

Corlius has successfully co-founded three medical device [00:01:00] startup companies, including Algiamed Technologies, and has a proven track record of driving disruptive growth in the field. Corlius holds postgraduate degrees in biomedical engineering and business. Pretty impressive. Pretty impressive. So I’m glad to connect with you.

Corlius Birkill: Thank you. Thank you, Dr. Garcia. It depends on the viewpoint, but yeah, thank you.

Dr. Freddys Garcia: You’re too modest. So Corlius, what inspired me to connect with you and interview for this is you guys put out a new piece of research, right? With more coming. And this one was titled, if I could read it here, Adaptive Autonomic and Neuroplastic Control in Diabetic Neuropathy, a Narrative Review.

So if I could go right into the questions, can I, can I jump right into this, Corlius? So the opening question is, and I like asking "why" questions? Cause I really want to understand why people are doing the things they’re doing, because listen, I’m surrounded by people doing research, it’s a labor of love.

You know what I’m saying? I can’t say the process is enjoyable for a lot of people, but the outcome is, right? [00:02:00] So what motivated you and the team to do this?

Corlius Birkill: Wow, Dr. Garcia, thanks. Thanks, thanks for asking the question. It’s an interesting question. Well, you know, to a large extent, Algiamed technologies is very research oriented, so we’ve got our own internal research team. We really actually enjoy research and we, we enjoy pushing the boundaries of our scientific understanding, especially when it comes to the nervous system. So, but specific to your question, you know, in around 2018, I went to attend the Peripheral Nerve Society meeting in the US.

With the specific intent of sharing some clinical results that we achieved with our Stimpod NMS460, and the results were pretty astounding, and quite compelling, and they were done by two different institutions at that point in time, one in the UK and one in South Africa. And it showed very compelling [00:03:00] results.

And you know, the results, were of a nature where the Stimpod was used for only three to six sessions and five minutes per each nerve for the lower limb. It’s really just two nerves, so common peroneal and tibial nerves and, indicated that we had tremendous amount of pain relief for up to six months or more for the individuals that were treated like that, so it’s a relatively short period of treatment time and very, very significant changes and changes that seem to last, you know, that’s not typical of any neuromodulation modality which is usually applied and then after a while, once it switched off, then the pain returns, so it’s just symptomatic relief, whereas this seemed to be something quite different. And when presented to the main thought leaders at the peripheral nerve society, surprisingly, or maybe unsurprisingly was, I was met with quite a bit of resistance in terms of the type of results that we achieved because it’s it’s unheard of especially in terms of the current standard of [00:04:00] care. And I soon realized that, the results is such a far outlier in terms of what is expected based on the current hypothesis of the pathogenesis, that it does not even make sense to a large extent and we really have to go back and investigate the current hypotheses in terms of pathogenesis of diabetic neuropathy and then try and redress it and try and figure out, how is it that we do see these results because the results are unmistakable, but the current hypotheses don’t provide for those results to exist. So somewhere there’s a disparity and it was our mission to figure out that disparity.

Dr. Freddys Garcia: I get it. You know, Corlius, I relate to what you’re saying because I’m very lucky, I get to be surrounded by all these very brilliant people and kind of like you and your team, they’re doing some research and some things. And some of my peers are submitting things for research and they had the same type of pushback being like, this doesn’t even make sense relative [00:05:00] to what is the norm that you’re getting the results that you’re getting.

And I feel blessed that I’m surrounded by these pioneering thought leaders, you being one of them, as I’ve gotten to know you over the last few years. I’ve told my story about myself in being exposed to your guys technology years ago. It took me years to catch up to what you guys were doing. Maybe I’ll tell that story at the end. So I, I totally get that part of the story. It’s not the first time I’ve heard that, but at the same time, I also think if you’re not getting resistance like that, then you’re probably not doing something exciting enough, right?

Like if you’re really doing something exciting, initially, people should say, Hmm. Is that even real? You know, like, is that even possible?

Corlius Birkill: Absolutely. I think what you’re saying is, is so true. I mean, it’s a validation of, of being a little disruptive, which I think we need, right? To push the boundaries of science.

So I absolutely resonate with that.

Dr. Freddys Garcia: If you’re not pushing the boundaries of science then science isn’t evolving, it’s literally, to me, it’s like part of the definition of it. Like you have to reevaluate everything all the time and, and to some degree, I think you’re, this paper, does that, like that’s [00:06:00] literally it’s purpose, but we’ll get into that.

So I’m gonna continue on. So here’s my question, right? Because I know we have lots of different people are gonna be either listening or watching this and the various levels of experience. So I’m gonna start at the beginning and I’m gonna start really simple and just Peripheral neuropathy.

At a simple level, what is it and what are the types of conditions that can cause peripheral neuropathy? Because it’s, there’s what people know and then there’s, it gets a little more complex than that. So what is it and what types of conditions can cause it?

Corlius Birkill: Yeah, thank you for that question. I do think that’s a good place to start.

So very simply, peripheral neuropathy is just an umbrella term for what is considered to be a peripheral nerve disease. And we’ll get into the word disease a little later on, because if I think if we deconstruct it, it leaves some clues in terms of the pathogenesis of neuropathy.

But basically what it implies is that structural changes occur within these nerves that changes the way that they function. [00:07:00] And there’s really two types of changes that occur. The first one is axonal degeneration. So the current thought is that, that something triggers or causes the axon of the nerve to deteriorate and actually die off.

Which is quite a terrifying thought, I think if you’re a sufferer of that peripheral neuropathy, because it means that the axon is gone, it’s dead and nothing can be done about it. So whatever symptoms you’re feeling, you’re going to be feeling for life, you know?

So, that’s the one type of change and then another structural type of change that could happen, that’s a second type of neuropathy, is when demyelination occurs. Obviously the myelin coating affects how signals are propagated, so the action potentials are formed, so when demyelination occurs, then it, it messes with how the signals travel to the neuron and, obviously de-modulates the [00:08:00] communication within the nervous system.

So those are really the two things that occur when peripheral neuropathy occurs.

Dr. Freddys Garcia: Okay now let’s shift that from just peripheral neuropathy to diabetic peripheral neuropathy. How is that different? Is it just how it started?

Corlius Birkill: Yeah, you know what? I just realized I didn’t answer the second part of your question and that’s actually gonna lead us into exactly where diabetic neuropathy fits in.

So yeah. let’s just talk about the different types of peripheral neuropathy as to your first question, second part of the first question. Type two diabetes is one of the leading causes of peripheral neuropathy.

It’s probably the most prevalent, but it also includes other things like vitamin and nutrient deficiencies will contribute to that, alcohol abuse, could have that effect, autoimmune and inflammatory conditions. I think most well known and probably not everybody knows this, that it actually has a strong neuropathic component [00:09:00] is rheumatoid arthritis.

There’s that, there’s medications and toxins, ironically, a lot of the times the medications that are used to try and bring neuropathy under control can cause secondary neuropathy. Also something like chemotherapy, and certain types of antibiotics even can cause neuropathy.

If we look at tumors, both malignant and benign, if they disrupt the peripheral nervous system, they can definitely cause neuropathy. Genetic conditions, there’s this odd genetic condition called the Charcot Marie Tooth disease that as, you know, it gets some exposure. Infections, probably the biggest one that we see and that we actually also treat with our devices, postherpetic neuralgia caused by shingles. Infections, viral infections, bacterial infections, that can cause radiculopathy and lingering nerve pain. Lyme disease is another, HIV even. I think lastly, and that’s why pain control and [00:10:00] trauma and surgery is so important, if pain persists subsequent to trauma or surgery for an extended period of time, then those nerves are at risk of becoming neuropathic.

Yeah, that’s a mouthful of different causes that I can think of right now.

Dr. Freddys Garcia: That’s pretty good at the top of your head. I felt like it was a board view class. I’m like, oh, that’s right! You reminded me of some that I should have, that I should have already known. That was great. So diabetic seems to be a big reason for that.

Let’s talk about how, what widespread this issue is. Like what are we looking at prevalence wise when it comes to these?

Corlius Birkill: To which one? To diabetic neuropathy?

Dr. Freddys Garcia: Yeah, let’s go to diabetic. That’s a very specific question. I would be impressed with your encyclopedia like knowledge if you were to cite both.

Corlius Birkill: Well, let’s think, I mean, the two are pretty related, actually, because diabetic neuropathy is the most prevalent. So I think for the world population, and depending on, on which source of literature you choose to quote, probably about [00:11:00] 7 to 10 percent of the population suffers from, some type of neuropathy.

Dr. Freddys Garcia: That is wild.

Corlius Birkill: Which is quite significant. It’s really significant, especially in the light of not really a lot of options, to treat these neuropathies at this point in time, and the absolutely debilitating effects that they have. People live in so much pain that they would rather end their own lives because they can’t cope with the pain and nothing happens for it.

It’s terrible pain. It’s terrible, burning, stinging pain, numbness, and all kinds of unpleasant things. Yeah, the worldwide prevalence, is like I said, is about probably about 7 to 10 percent. Interestingly, in all cases, that the prevalence increases above the age of 45. So, yeah, discriminating against older people.

But speaking specifically about diabetic neuropathy, interestingly, if we’re looking at the U.S., it’s about 1 in 10 people, about 10 percent of the population that suffers from type [00:12:00] 2 diabetes. Whereas worldwide, that figure drops a little bit to 7%, but there is a massive, contingent of that high percentage in Southeast Asia as well and in Europe, so still more common with people over the age of 45. And of that 10 percent in the U. S. that suffers from type two diabetes, about 40 to 50 percent of those individuals suffer from diabetic peripheral neuropathy. That’s a lot of people.

Dr. Freddys Garcia: That is a lot of people.

Corlius Birkill: That is a lot of people.

And the scariest thing, actually, Freddys is that despite its existing pandemic proportions, if you look at how it’s going to grow, it’s projected to grow over the next 25 years, we’re looking at that population to triple. So people suffering from type two diabetes will increase to about 30 percent of the world population.

That is, or in the US at least, probably about 21 percent in the world. Which is a [00:13:00] terrifying number. It’s a terrifying number. I mean, that’s like 10 percent of the population at the very least will suffer from peripheral neuropathy. That is a massive number.

Dr. Freddys Garcia: Yeah. Good old US of A leading the way though!.

So something we don’t want to lead the way in.

Corlius Birkill: No, no, please. Let’s try and get it under control. I hope we’re contributing to the ways of getting on top of this thing. Yeah.

Dr. Freddys Garcia: Talking about ways to get on top of this thing, let’s talk about what is the standard of care?

Let’s talk about it from the medical perspective, right? So we’re talking pharmacology. What about a manual therapy perspective? And nutritionally what are people doing out there to tackle this condition and subset of diseases?

Corlius Birkill: So that’s an interesting question. And I just want to go back to the current hypotheses.

The current hypothesis is that doesn’t matter what and we’ll discuss the two mechanisms a little later of the current hypotheses, but either one of them, basically says that the nerve cells die in it. [00:14:00] Okay. So.

Dr. Freddys Garcia: That’s what I was taught!

Corlius Birkill: That’s a, that’s a no return.

Like you get it and you’re done. And really the standard of care, attempts to do two things. So in the first place, it’s preventative care to try and prevent further neuropathy to form. And in the case of diabetes, that’s done by attempt to bring down the hyperglycemia. And those are what you mentioned, those are typically the lifestyle choices, nutrition, exercise, some other interventions like that to attempt to reduce the impact of the hyperglycemia and the hyperglycemia itself. But unfortunately for those people currently suffering from diabetic neuropathy to the extent of their suffering to the neuropathy, they’re left with limited options.

So, neuropathic pain, for instance, doesn’t respond consistently to classical non opioid analgesic drugs. It’s better treated, or the standard of [00:15:00] care involves co analgesic drugs, such, such as antidepressants and anticonvulsants, which are, are quite significant interventions. And under certain conditions, however, neuropathic pain has to be treated with opioids.

So even on a chronic basis. And that’s a tough one. We all know about the impact of opioids. So typically what happens is the first line treatment is probably anticonvulsants, medicines typically used for treating epilepsy, such as Gabapentin and pregabalin. So that’s usually first line treatment.

If that does not have significant results, antidepressants are added to the cocktail. And if that doesn’t have significant results, then opioids are added to the cocktail. So that is quite a rough cocktail at the end of the day. And the cost of the healthcare is pretty significant. I’ll have you guess, Freddys, how much does that cost per year per person suffering from diabetic neuropathy in the U.S.? [00:16:00]

Dr. Freddys Garcia: Was this in your guys paper? I think I should know this.

Corlius Birkill: Just take a wild guess.

Dr. Freddys Garcia: I mean, for that much, for that cocktail, which you’re right, it’s a little, a little scary there. Um, six, $7,000, I would think that medication is for the year.

Corlius Birkill: Wow. That’s a good thing you’re sitting down. It’s about $35,000 per year.

Dr. Freddys Garcia: That would be crippling to a family.

Corlius Birkill: It is not only crippling to your family, but also to the healthcare system in the US. It is such a significant impact and that for something that has a very limited effect.

It’s not like it takes the neuropathy away and in a lot of cases, even causes secondary neuropathy. So it’s part of why we got involved with this, it just feels like in this day and age, we should be able to come up with better solutions, right?

Dr. Freddys Garcia: For sure. So that’s medical perspective.

What about manual therapists? Are they able to tackle this? Or what [00:17:00] about nutritional? Can they dent this? Can they dent it and, and why is it still a problem? I guess that’s why you guys did the paper, right? We go, we got to think about this problem differently.

Corlius Birkill: Yeah, indeed.

So unfortunately, like I said, those lifestyle choices that, that can be made with regards to nutrition exercises, all of that, that is just to prevent the further spread of diabetic neuropathy. And those are difficult. That’s a significant lifestyle changes. So oftentimes not very sustainable.

Preventative care is the best way to go about it. I do know that there’s a massive awareness campaigns around it to try and educate people also just to have a better lifestyle choices. Prevention is probably currently the best option.

Dr. Freddys Garcia: So Corlius, you went back to a statement and remind me, and I think I even spoke up and said, Hey, that’s what I was taught. I was taught that the nerves were dying off in like this diabetic peripheral neuropathy, right? Like they’re, you know, like they’re, they’re dying off and [00:18:00] they’re coming backwards.

So like you get the, the distribution becomes even bigger and it’s like, that’s it. Is, is that an accurate statement? You know, are the nerves dying off? And I guess that begs the question, can they be recovered if they are dying off? Like, is it as bad as the words I’m saying make it sound?

Corlius Birkill: Yeah, I think, Freddys that there’s the big fundamental premise of the research that we have done.

Maybe I should just digress a little bit and just tell you what those premises are. So when we approached our research, there’s a couple of fundamental things that we believe in that we need to satisfy throughout the progression of our research and those became like three pillars of our research that we always have to check in with to see if we abide to them, the first one is that we firmly believe that body is highly intelligent.

And it always attempts to correct any pathogenic assault to achieve a [00:19:00] favorable homeostasis. The body is programmed to always move towards homeostasis, even in the, in the face of a pathogenic assault. But we don’t believe that the body’s first reaction is to kill itself in the presence of a pathogenic assault.

So it’s a tough one for us to swallow to believe that the nerves actually commit suicide. They see the hyperglycemia and they’re like, Oh no, we’re out of here. This is not good for us. We’re done. We’re moving on. That was the fundamental premise that we worked with was that the body would not, there’s no reason for the body to do that.

The body is more intelligent than that, and it’s going to try and respond in a way to fix itself. The second thing that we ran into, and we soon ran into it, the whole research is based on a literature review of about 170 something papers, spanning research over the past 30 years of pathogenesis of diabetic neuropathy.

And [00:20:00] we came across a situation quite early on in the research where we realized things don’t always temporarily align, so for instance, one of the hypothesis is that the vasculature degeneration, or deteriorization is responsible for a shortage of nutrients and oxygen and everything being supplied to the nerves, and then the nerves die as a consequence of that. Yet in several instances, diabetic neuropathy, occurs prior to the vasculature damage. So they don’t necessarily temporarily align, they’ve been instances like that where we’re like, in some cases they do, in some cases they don’t. So, how do we account for that? Even if it’s outliers, we have to be able to account for it.

So, whatever hypothesis we came up with had to align temporarily, had to make sense. And then at some point, we ran into some obstacles where just not enough information [00:21:00] was available, not enough research had been done on the gaps that we were trying to fulfill, or fill. So, what we decided there was to then take other diseases, especially diseases that, type 2 diabetes or even type 1 is a comorbidity factor for, because the moment you’ve got comorbidity happening, then it means that some of the mechanisms are similar, and the one makes it worse.

Prime example is really COVID, which has been studied extensively over the past few years. And diabetes is a comorbidity factor for that. So it means there’s some mechanism that already exists in diabetes that is exacerbated. With the onset of COVID the way that the body reacts is a similar mechanism.

So we looked into when we got stuck, we would look into these different principles of other types of diseases and their pathogenesis and try and [00:22:00] figure out what what matches and what we might be missing with the pathogenesis hypotheses with regards to diabetes. So those were the three pillars of the research.

I must admit, I forgot your original question. I don’t know if I’ve answered it.

Dr. Freddys Garcia: We actually got into the nerves and whether they die off. And then you were going into the model of how to understand..

Corlius Birkill: Right? Yeah, I think, what’s probably just pertinent at this point in time to mention is just a specific mechanism of the two current hypotheses, prior to our paper.

And yeah, the one is just very simply, I briefly touched on that is that, the vasculature deteriorates. There’s not enough nutrients, oxygen for the nerves and nerves die because of that. Okay. And I said that there’s already complications with that hypotheses. And then the second hypothesis is that, there’s an epigenetic response based on the hyperglycemia.

So somehow the hyperglycemia puts the mitochondria in shock and the [00:23:00] mitochondria decides this, is it apoptosis, we’re done. Suicide is the only option. So that’s really the two current running hypotheses

Dr. Freddys Garcia: You guys published this paper, and the whole idea was to update the understanding of the pathophysiology of diabetic peripheral neuropathy. So, if those are the, those are the current understandings of diabetic peripheral neuropathy, what does this updated model propose? Like what did your paper come out to?

And I know in the paper, you guys spoke to a couple of different areas in regards to, the autonomic and inflammatory response and then even neuroplastic adaptation, which as a neuro guy, love that. Can you speak to both of those in regards to how the paper built out a more modern model for understanding the disease?

Corlius Birkill: Absolutely. Thank you. The paper is quite extensive in this and I don’t think we have the time to go into depth. So I’ll just highlight a couple of points. We actually went and [00:24:00] and said, I think the first departure point was to separate the autonomic and inflammatory responses.

And to say these are two, the auto autonomic inflammatory response and the neuroplastic adaptation. And we say that these are two control systems, in their own right, responding to the same, assault, which in this case is hyperglycemia, and they handle it differently. And they work in parallel and in some instances, there’s a little bit of overlap from the one to the other, but it’s quite possible that the one progresses without the one other one being triggered at all, and vice versa.

So sometimes you can have an inflammatory response, which is quite severe and you don’t have any neuroplastic response, which accounts for the fact that a lot of people with diabetes actually don’t have neuropathy. And then you can have the same the opposite way. So you can have a very early onset of diabetic neuropathy.[00:25:00]

And peripheral neuropathy and actually have a delayed action with the inflammatory response. So these are two separate control systems, which are operating differently and triggered differently based on different, genetic makeup of different people. And the moment we introduced this concept, we start accounting for a lot of anomalies with the current understanding , and there are a few of them, but yeah, just to speak to each one of these, so in the paper we actually take them all the way through. We look at the autonomic and inflammatory response first, and we look at it from the time of a glucose spike all the way to like pre-diabetes, and then the chronification of the whole process and symptomatology where you get to actual diabetes and we address the progression and the adaptations and maladaptations and each one of these stages. And quite interestingly, the body’s got a tremendously intelligent response and just if I can speak to that for a second with the autonomic and inflammatory response, [00:26:00] the very first thing that the body does in the presence of hyperglycemia is actually resorts to vasodilation and it increases the blood volume.

So it’s saying, there’s a partial concentration of toxic levels of hyperglycemia in the blood that is being spiked. And it says, well, it’s not too difficult to deal with. Let’s just increase the blood volume and relatively decrease the presence of the toxicity or the percentage of hyperglycemia.

So the body does that. And I think that’s quite intelligent. So after a little while of this and when it doesn’t resolve, then basically the cholinergic anti inflammatory pathway is triggered. And then an inflammatory response is triggered, which is a healthy response. When the cytokines are expressed and it’s expressed as a, as balanced adaptation.

It’s very healing. It’s a very good thing for the body. [00:27:00] Absolutely necessary. And I mean, that’s why after injury, we don’t resort to anti inflammatory drugs. Because then we stop the healing process, right? So it’s got to get some time to do its thing. It’s an important thing.

It’s a healing process. But then as we know, I think everybody’s aware of it, the term is cytokine storm after COVID. The moment that control system is overwhelmed, and it starts maladapting, then it’s, it, it really starts to spin out of control. And the cytokines are overexpressed, and when that happens, vasculature deteriorates.

So then we start seeing vascular damage. And that’s a simple progression of what we are seeing in the inflammatory response in the autonomic response and control system. Which eventually progresses, progresses, later on when the cytokines are overexpressed and way late into the neuroplastic adaptation, we get a situation where the inflammatory response also [00:28:00] starts causing demyelination of like motor nerves later on.

So, there is some overlap between the two systems, so we’re not saying they’re two completely separate systems. But, essentially, they react very differently, and especially in the, in the beginning stages of diabetic neuropathy. So when we move to the neuroplastic adaptation, again, I want to emphasize that body is an extremely intelligent capacity to react to a toxic assault.

And the first thing, and this is actually not in the paper. It’s something we address in a follow up paper where we go specifically into the gene expression and epigenetic process of how this whole thing ties up. And you can look out for that. It’s nearing completion, but it’s extremely interesting.

You know, the ionic gradient across the membrane, which usually has very specific characteristics with a healthy action potential being created, that changes with [00:29:00] hyperglycemia. And the nerve immediately recognizes it. It’s like, oh, the ions are different now outside the membrane and the gradient across the membrane has changed and the membrane reacts to that and the way it reacts to it and it’s interesting because the membrane is intelligent enough to react to it. It’s not even dictated by the mitochondria. Which is really where the software of the nerve is, right? With regards to the epigenetic expression, and, or the gene expression, and What happens on the membrane immediately is that the little protein gates that open for the sodium potassium, those channels to create the action potential, they actually start moving on the membrane.

They’re mobile, they move up and down and they’re like, okay, well, something is not great over here. So maybe there’s an injury or, or it’s a localized assault on the membrane. So let’s just move up a little bit and all of them move and they move around to make sure that it’s the whole brain membrane that’s affected.

[00:30:00] By that time, then the decision making process reaches the mitochondria and it becomes more centralized within the peripheral nerve. Not the central nervous system even yet, but just in the peripheral nerve. So now the peripheral nerve says, we’ve got so many dendrites that are now hyper excited and they just go crazy, they’re just firing.

So, let’s figure out, we’ve now moved around these little gates and they seem to be okay. It seems to be a unified attack on this whole thing with this pathogen. So, now it says, okay, let’s assume that all the dendrites are damaged. And then let’s grow out new ones. So it regenerates and starts into a phase where it grows out new dendrites.

The intelligence behind it is that the moment you do that, now you get the benefit of spatial summation or the law of averages, because now the nerve takes all the inputs of the [00:31:00] dendrites that it thinks is damaged, plus the new healthy dendrites. And then, if that was the case, then the excitability should have dropped overall.

Okay. If that makes sense. But obviously the assault is still uniform on all the dendrites. So all the dendrites are exposed to the hyperglycemia and they all become hyper excited. So the nerve is confused. It’s like running out of tricks. And at this point in time, the central nervous system is starting to get involved.

And it’s like, damn, this, this nerve, this nerve is making a massive noise. And we, you know, it can’t be like that all the time. So you start getting central adaptation in the spinal thalamic tract, all the way up to the central nervous system in the brain, you start getting changes on how these signals are received and perceived, and eventually the peripheral nerve says, you know what, none of my tricks are working.

So I’m just going to change my structure so that I shut [00:32:00] down a little bit. Okay, so I’m just not going to make a noise anymore. So it retracts its dendrites and it does change the structure of its axon, but it doesn’t actually die. You know, nothing has caused it to die. It doesn’t die. It’s still there.

It’s made structural changes and due to its neuroplastic adaptation, so the epigenetic expression within the software, just put another way, the software of the nerve has triggered it to change its structure in a way that it’s not going to make that noise. So I think our big departure point there is that it doesn’t actually die.

It’s just a structural change. And just because there’s a structural change to the axon doesn’t mean that the nerve is dead. The whole progression then through the central nervous system and eventually, the efferent pathway down to the motor nerves, there’s adaptation all the way in all the different stages all the way down to the motor nerves and by the time that the motor nerves are affected, [00:33:00] then there’s some crossover with demyelination occurring and there’s other adaptations that occur as well with structural changes.

I think, in essence, that’s really it.

Dr. Freddys Garcia: This is making my head because, you know, we’re always teaching a sensory evaluation before a motor exam, but you really just took us through this whole autonomic component all the way to the inflammatory response and how they lead to each other and then you’re really going into, when you say neuroplastic adaptation you really you took us all the way there right from sensory back out to motor and and how they adapted locally but then there are going to be central nervous system changes from a sensory input change.

I mean a lot of what we do in functional neurology is stimulating receptors right getting information from the outside and based off that information you’re going to have a motor output all the way down to emotion. Right? I like that picture you, you painted. I like that understanding of it.

And I thank you for speaking to whether the things die off or not. Because in my mind, I always pictured it like, like striking a match. You know how you strike [00:34:00] a match and the match burn, burns back? That’s what I pictured was happening to the nerves. So having your paper update this model, I think, is a little bit exciting.

So, now that your paper updates our way of thinking about diabetic peripheral neuropathy, I guess it begs the question, does this allow to think of new applications or treatments that could be more effective than everything that’s happening now? Which, you know, doesn’t sound like it’s been great in solving the problem since it’s a problem that’s been around for a long time.

So, does this give us some new ideas, and I guess the follow up question to that would be is if we, if we adopt this new way of thinking about the disease, should patients have hope for a different outcome if everybody buys into this more modern model for understanding the disease?

Corlius Birkill: Yeah, thank you for that. In short, the answer is yes. And I think it’s maybe a good place to start [00:35:00] is just, the purpose of our research at Algiamed is very much based on looking at the underlying biological processes and disease states and how they can be modulated or, in this case, with the structural changes being remodeled due to the application of electromagnetic fields.

This is really what we’re looking at and it’s what I’m speaking to when we talk about new therapies. \ The reason we focus on the electromagnetic fields is really for a couple of different reasons. We have a fundamental belief that we can affect the neuro humoral system in as effective ways as a pharmacological approach, yet it can be more targeted and most importantly, it’s inherently safe due to the fact that when you stop the treatment, it’s switched off and nothing is left back in the body. So there’s no side effects.

Dr. Freddys Garcia: Can’t say that about all pharmacology, can we?

Corlius Birkill: Yeah, but at the same time, I’m just qualifying my statement now because I’m not a pharmacologist. I’m a biomedical engineer [00:36:00] and I, I can only speak to electromagnetic fields. I can tell you why I think they’re preferable, so just limiting myself, my commentary to electromagnetic fields. I can tell you that, we do know that pulse radio frequency at very specific frequencies and very specific amplitudes based on other research that we’ve done that will be published in the near future, actually does have an effect on the gene expression and triggers an epigenetic process within the nerve itself.

The immediate question is, how do we know that? The answer is simple. There is certain epigenetic markers or gene expression markers, such as c-Fos, for instance. c-Fos is a amino reactive indicator and a marker. So it says that. the mitochondria is undergoing some gene expression changes, being stressed, or it’s reacting to some input and something’s happening.

Interestingly, it keeps on being expressed up to about seven days [00:37:00] after pulse radio frequency has been applied. So it’s not a short term thing, and that’s why the therapy is so unique because you only have to treat for, you only have to trigger a process. It’s a cascading process that will occur and keep on occurring over time.

So it’s not just relevant for the period of stimulation. And that’s even more so if you look at the activating transmission factor three, ATF3. So that keeps on being expressed up to about 14 days after the treatment and it’s very interesting because that’s associated with structural changes with the cell body of neurons and specifically A delta and C fibers.

So the smaller fibers. So somehow seems to selectively target them first. So we very familiar. It’s common knowledge that post radiofrequency does facilitate this, the structural changes and actually triggers this mitochondrial response or gene expression on the epigenetic cascade, if you will. So [00:38:00] yes, from an electromagnetic point of view and looking at the clinical results that we achieved with our device, it makes sense.

You know, it is plausible to say that we can reset for just a plain, plain term, maybe get the nerve to reset to its factory default. And then grow itself back. Again, we don’t believe it’s dead. So and certainly our clinical results support that, that thinking.

Dr. Freddys Garcia: So clinically you’re saying, I like the way you said that because when you’re saying this, I envision like, the pulse radio frequency or transcutaneous pulse radio frequency.

It’s almost like a set of dominoes, right? Like it’s setting off this reaction through that input that lasts longer than the actual therapy lasts. And you know, and we’re talking about the transcutaneous pulse radio frequency. What the device outputs, but we haven’t really even talked about the device, right?

Because we were wanting to talk about the research, but Corlius, I think at this point, I have to give you an opportunity to [00:39:00] really talk about the device because I think that becomes a natural progression when you’re saying, hold on, this is even possible, right? Because I think a lot of doctors who are treating this condition right now are kind of being, hold on, this is exciting, right?

We have a different way of thinking about the condition and there’s just technology out there that has that has shown clinical outcomes to be really, really favorable. So can you speak to this device and kind of describe it and how doctors are using it? And I know they could use it for more things than just peripheral neuropathy, but I guess in this conversation we’ll frame it for peripheral neuropathy.

Can you speak to that?

Corlius Birkill: Yes, sure. Yeah, 100%. Freddys so very simply, we’ve come up with a very specific waveform because the moment you do pulse radio frequency transcutaneously, then there’s certain limitations that you have to bear in mind. And so just to mention very briefly that pulse rate of frequency as such, that when it’s applied transcutaneously, you won’t even feel it.

It’s not even going to create a fasiculation or a sensation or anything because the frequency is so [00:40:00] high, it cannot create an action potential. It just vibrates the ions. It’s not mobilizing ions in a certain direction that’s going to cause an ionic gradient over the membrane that will trigger an action potential.

So there’s another component to the waveform that we’ve introduced in a device, and it’s often confusing because then It may lead people to think that it’s a tense device. We have a nerve locating square wave, which is used to create a sensation, number one, and secondly to create a fasciculation with the associated muscle with the nerve that we’re treating, but that’s a nerve location section of the device, that you can feel and it will cause a little contraction of the associated muscle. of the nerve that you’re locating, that you’re looking for. That is not a therapeutic effect. And it can’t be because if it was, then we would see very similar results with TENS, which we don’t things based on TENS kind of waveforms, including all the way up the ladder of [00:41:00] technology, all the way to spinal cord stimulation, which we simply don’t see.

So, with regards to the pulse radio frequency section, when we introduce that part of the waveform, then the tip of our pen that touches the skin actually, is not an electrode anymore. It actually acts more like an antenna. And when an electromagnetic field travels through space or through the body, the magnetic component sees the body as a homogenous substance.

So it propagates very evenly through the body. However, because of the frequency factors, it can only propagate deep through the skin interface if it’s a high frequency. Because the skin interface it acts as a high pass filter. So that TENS-like like signals can’t even penetrate to the depth that we needed to penetrate.

And then interestingly, because of the way that the electromagnetic field propagates it, it gets induced into the axoplasm of the neuron and once it’s induced there, it changes properties and gets trapped in the [00:42:00] axoplasm and acts as a wave guide in the propagation in the axoplasm.

So that electromagnetic field gets stuck within the tube of the nerve. And then propagates in there and interestingly, there’s another limiting factor there because, there, the axoplasm and the propagation of the electromagnetic field there acts as a low pass filter. So the frequency has got to be exact. It’s got to be a very specific frequency to be able to get that waveform to be induced into the axoplasm, then reach the multiple mitochondria within the nerve itself.

Then there’s a second component to it, and that is it has to be exactly the right amplitude. And so those are things that we that we address, and we’ve come up with solutions with our proprietary waveform that actually addresses that. You know, interestingly, we say we treat for 5 to 10 minutes, but really to trigger that cascade, we need one pulse.

We only need one pulse of 200 [00:43:00] milliseconds.

Dr. Freddys Garcia: That is wild!

Corlius Birkill: Yeah. Point, 0.1 or 0.2 milliseconds wide. So that’s all we need, but the only reason why we keep on repeating it is to improve the statistical chance of getting exactly the right amplitude to hit that mitochondria. So we have some providers that act actually only treat for about 30 seconds or so and get very, very significant results.

It’s a completely different technology. All we’re doing is we are just triggering an epigenetic response from the mitochondria. We are resetting the software to the factory default of the nerve.

Dr. Freddys Garcia: That is, it’s incredible. And I’ll, I’ll tell my story here. You know, when I learned about the technology that you’re talking about right now. I looked at it, I kind of forget how many years ago, four or five years ago. And because of the form factor, I thought it was another electro neuromodulation type device, just like, you know, the ones that are out there. And certainly, and it wasn’t until the last six months or so through, the Pain Reset program, we were talking about chronic pain and how to tackle that problem, which is not the subject of this podcast, but you [00:44:00] guys actually have contributions there as well, did I come back to the technology you guys are pioneering and then go, " Oh, I missed, I missed the boat.&quote;

I did not understand what you guys were actually doing because I saw a fasciculation. But now that I understand that the fasciculation was the means to know that you’re in the right place, the magic, if I want to say it that way, is through the pulse radio frequency. That light bulb went off and then I started playing with this more and then saw the clinical results and then the light bulbs are going off in the patients and the other educators that it was in the room with.

Everybody was going, hold on one second. This is a different, this is a different beast. You know, a couple of minutes ago, I asked you, are there, does your updated model allow for different treatments? And obviously to me the answer is yes, because you guys are pioneering in those areas for treatments and I think this creates a lot of hope for patients and therefore clinicians who want to have better clinical success.

What you guys are [00:45:00] pioneering is absolutely exciting. And I know you’re looking at other conditions as well in a very, regimented, evidence-backed way, which is the way to do it. You know, for you to be pushing the envelope in regards to health care, for you to be tackling these conditions, for you to say, Hey, not only we’re going to create technology to support these conditions, but we’re going to do research and try to understand these conditions better.

I got to tell you, Corlius, it makes me admire you for the work that you and your team are doing. I mean, you guys are doing it right. And it’s impressive. It’s just, it’s just impressive. If people want to learn more about you, the company and the technology, the device itself, even where do they, where do they do that?

Corlius Birkill: Well, you see the signage of the company right here behind me. I hope it’s been noticed. So it’s Algiamed and you can find us on Algiamed.com.

Dr. Freddys Garcia: Okay. Excellent.

Corlius, thank you so much for your time today. Thank you for letting me pick your brain and congratulations on that paper being [00:46:00] published.

It was wonderful. I enjoyed reading it. And I look forward to the future ones because I think you guys are really onto something. And I hope people read this and understand that this is the tip of the iceberg. Like you guys are going to tackle some problems that are just like peripheral neuropathy, maybe have not had great success elsewhere, but the way you guys are doing it.

It is exciting. So I’m excited for what’s coming next.

Corlius Birkill: Yeah, so am I. So am I. Listen, thank you so much. It’s been an absolute privilege to have this discussion with you. And thank you. Thank you for expressing your appreciation for what we do, you know, a lot of times, I get the comment that we’re actually predominantly a research company and it certainly is a massive passion of ours.

We need to understand the mechanisms of how these things work if we’re going to improve it and if we’re going to come up with better solutions for the people who suffer from these things. So thank you very much for that. I really appreciate the opportunity.

Dr. Freddys Garcia: My pleasure, Corlius.

So again, if you want to learn more about Corlius’ team and the technologies of the [00:47:00] Stimpod NMS460, just go to Algiamed.com. That is A L G I A M E D, dot com. And Corlius, I have a feeling I’m going to probably ask you to come back on for the future papers as well, because we have to keep sharing this information.

It’s important.

Corlius Birkill: Thank you. Thank you. Be happy to, we really coming up with some exciting stuff. So please have a look at our research page on our, on our website to keep you updated. There’s actually a list of the projects that we currently ensuing and how we are progressing with them.

Dr. Freddys Garcia: Excellent. Oh, you know what? I’m going to check it out right after this. All right. Thank you, everybody. Thank you for listening to us and we hope we’ll catch you all next time on another episode of Talk Neuro to Me. Thank you everybody.

Thank you.

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