Marc Mathys, CNS Therapy: 0:00

Our goal is to eliminate the pain.

Alex X-Health.show: 0:02

Like, completely?

Marc Mathys, CNS Therapy: 0:03

Completely.

Alex X-Health.show: 0:07

Hi, I'm Alex and welcome to the X-Health.show where I talk to visionaries behind the latest innovations in healthcare. For the eXtra health of the future. We're sitting at a comfy coffee table space at the center of Switzerland Innovation Park Basel Area Jura, where MedTech meets high-precision industry. My guest today is Mark Mathys. He's the CEO of CNS therapy. He dropped his attorney career in Ventura, US, embraced his engineering background, and started undergraduate research in Marburg, Germany, to found a startup in Switzerland. CNS Therapy is on the mission to eliminate chronic pain. They use electric stimulation combined with behavioral therapy. No painkillers, no opioids, no cannabis. They call it Systolic Extension Training or SET. You'll hear how to get rid of pain using science, about physiological mechanisms of pain, fibromyalgia, neuromodulation. Trigger warning, suicidal thoughts will be mentioned at the beginning.[INTRO ENDS] I usually start with a question but Marc, let me start this time with a story that breaks my heart really. Um, when preparing for this episode, I reached out to a friend I haven't seen for years but we're in contact on Instagram. She's one of these human beings you want to be among. Like, highly sociable, smiling, intelligent, she speaks... I thought she speaks four languages. But then I was like, oh, I'll check it on her LinkedIn: so four languages– native or bilingual, six additional – professional working proficiency, plus two more – limited working proficiency. I mean, highly intelligent human being.

Marc Mathys, CNS Therapy: 1:51

Wow.

Alex X-Health.show: 1:51

Yeah, totally. So I knew she has fibromyalgia, the illness that you may actually treat with your

Marc Mathys, CNS Therapy: 1:54

Yes. SET device. She recorded a message for me, because it was

Alex X-Health.show: 2:02

So let me first start with the pain and one of these days that she called "flare up" or crisis. And she wasn't able to have a conversation. And well, this is

what she said about the pain: 2:15

You are always in pain. But there is a day or two in a month, and you never know what triggers it, stress at work or a quarrel, that you're literally losing your mind – it hurts so much. So the whole body hurts.

She said: 2:36

You literally think, I'm going to jump out of a f... window. Can you imagine going through such a pain each month for more than a decade? She was diagnosed at the age of 27, a few years after we met. And she says in this recording, you know, you cannot work, you cannot travel, you cannot have sex, you cannot be touched. And then she said, Sometimes your body turns on your own opioid-like substances, endorphins, enkephalins, and dynorphins, and then you feel stoned. And this is when the vision gets blurry, you laugh and cry at the same time. So we take opioids like Tramadol, for example, to have things under control. And this is something that I was on the verge of crying when she was saying that. You've got to get used to the fact that you will live with pain forever. She's a bit better now. She went back to work. She takes a painkiller and antidepressant, sleeping medicine, Tramadol when she needs it, does yoga, Japanese dance, and calligraphy to lower cortisol level. But the thing that she said, Live with that forever, was actually... it's terrifying. And you work actually on something that may stop this pain. how pain can become chronic. You research that?

Marc Mathys, CNS Therapy: 4:29

Yes. Well, first, let me say that she should come to us. She would have to come to the University of Marburg to get treated because we treat patients like her. And, unfortunately, the story is all too common. And also, unfortunately, once she gets into the medical community, she is treated palliatively and she is treated in such a way that she'll have the pain for the rest of her life. We don't believe that. We think there's ways for her to get rid of her pain. And so I would recommend that she come see us. Unfortunately, it's not a fast process, it would take about five weeks – 20 hours of treatment – but we would, you know, love to treat her. And those are the type of patients that we do treat.

Alex X-Health.show: 5:24

Awesome to hear that, totally, thank you.

Marc Mathys, CNS Therapy: 5:27

As far as the second question, which was, how does pain chronify, there's been a lot of research done in this area. And the chronification of pain is both a psychological process and a biological process. That is, if you examine a chronic pain patient, you do see structural differences in the brain, in the peripheral area and in the dorsal horn. So there's changes throughout the body and the brain. On the other hand, from a psychological point of view, pain patients tend to be hyper vigilant, they're also hypersensitive, and generally, their pain tolerances will be less than a healthy control or than a normal person. And one of the things that we do through our training is we attack both this biological process and the psychological process. And we strongly feel that both of those two sides need to be addressed.

Alex X-Health.show: 6:42

What does the mechanism to inhibit pain? Because when pain becomes chronic, when I was preparing for this conversation I read that there are some mechanisms to inhibit the pain, and they actually fail at some point.

Marc Mathys, CNS Therapy: 7:00

Yes, the normal mechanism to inhibit pain has to do with a flood of biochemicals, neurotransmitters, that the brain releases, typically would be in a fight or flight response. If you're in a fight, you don't feel pain, you may feel it later. Or if you're trying to hit a soccer ball through a door, again, you don't feel the pain, if somebody kicks you, then you'll feel it later. And so we do have neurotransmitters that reduce or actually eliminate that pain. However, the body can only produce those neurotransmitters for a certain amount of time, it can't keep producing them. And with a chronic pain patient, they're in pain all the time and so that mechanism of reducing pain or inhibiting pain doesn't work anymore. Medical science has spent 50 years trying to attack the pain problem by cutting off noxious input coming from the body into the brain. And they've done that with back fusions, spinal cord implants, nerve denervation, opioids, and a bunch of other methodology. And it hasn't worked. The experience has been lackluster, the trials show some reduction in pain, but the pain doesn't go away. And I think the big realization is that pain is not an input. Pain's an output. It's what you feel. That output is only loosely related to the input that's coming up from the body. And in a normal situation, if the input coming up from the body is not providing information than the brain turns it off. And high percentage of what you experience each day doesn't come to your attention. You're probably not feeling your shoes right now. Because there's no reason to feel them until I mentioned your shoes.

Alex X-Health.show: 9:17

Of course, I do feel them very much now. I feel all my toes.

Marc Mathys, CNS Therapy: 9:20

Exactly. And so what happened, I changed your attention. Now, usually, patients if they have a problem that's chronic, they turn it off automatically. These patients aren't turning it off for whatever reason. And the way to understand that is to look at a 90 year old. The 90 year old has massive systems failure, just due to age throughout his body, yet most 90 year olds are not in chronic pain. Why not? The body's telling him look, I'm all screwed up. But they're still not in pain. And so this idea that we can kill pain by getting rid of the noxious input is just wrong. And that's what's driven sort of medical technology.

Alex X-Health.show: 10:10

What do you mean by input?

Marc Mathys, CNS Therapy: 10:12

The input is the sensory signals and nerve signals that are coming from the body to the brain.

Alex X-Health.show: 10:20

So what's your solution then? How does it work? Or what does it look like? Yeah, let's first maybe say about the device what's involved in it.

Marc Mathys, CNS Therapy: 10:33

Okay, so it's a medical device. And what it does is it takes an EKG, which is the the electrical signal that the heart produces, and it sends to the hand – to the thumb and to the ring finger– short 118-milliseconds electrical pulses. And the electrical pulses depend on the patient. Because everybody's pain tolerances are different. By the time you feel the pulse, it's already gone. But nevertheless, what happens is, the brain reacts since pain is the body's most important warning signal. And it starts instituting some of these inhibitory mechanisms, which aren't working, because they're in constant pain, but the pain we actually initiate, which again, is controlled by the patient, is a higher level of pain than what they're experiencing on a daily basis. And so we basically interval train that inhibitory mechanism in the brain. The goal is to reset their mechanisms to inhibit pain.

Alex X-Health.show: 12:06

So you treat pain with pain. But how do you administer this pain? When do you... how much does it hurt? I have so many questions about that. How much does it hurt? And well, is there any specific setup about that?

Marc Mathys, CNS Therapy: 12:28

Yeah. So typically, a patient will come to us, we put them in an easy chair, we tell them to relax, we let them relax a few minutes, and then we attach five

cables: 12:39

three cables go on the body, to pick up the EKG and two cables go one to the ring finger and one to the thumb. And that's the setup. Then we go through a rating procedure. We give them a very low current on their fingers and see if they notice anything, it starts at 200 micrograms. They don't notice anything at that point, it's below their sensitivity threshold. We increase that by 200 micro and ask them again, do they feel something. Typically, no, maybe yes. And when they start feeling something, that's the sensitivity threshold. Then we keep increasing at the same rate until they say that it's painful. That's a pain rating of zero on a scale of 0 to 10. And we keep increasing. And we're asking, Did you feel that? What would you rate it?, until at some point, they tell us it's a 10 and I really don't want to go any further. So that's the way we dial in what the patients feel. Once we have those three numbers, the sensitivity threshold, the pain threshold, and the pain tolerance, we back off the high number and that sets the amplitude for the stimulation. Now, we vary the stimulation because the brain adapts very, very quickly. And so we want to sort of surprise the brain. So we do it pseudo randomly. But then we give a series of 60 stimuli at various intensities and at various time points, and then we do the rating again. Because even in that short amount of time, which is about eight minutes, those tolerances will have changed. So we measure the tolerance again, and we do it again for another eight minutes to 60 pulses, and then we rate a third time just to keep track of the data. And that would be a typical stimulation session.

Alex X-Health.show: 14:43

Because we get used to the pain or...

Marc Mathys, CNS Therapy: 14:47

Your brain adapts very quickly. And there's another side benefit. The patients come in, they're hypersensitive to pain. And when they see that their sensitivities change objectively by looking at these bio signals, then they see improvement just in one session they'll see improvement. When they come back for the second session, some of that improvement will have gone and when we start the process again. And over the sort of 10 sessions in the five weeks, they significantly change their pain sensitivity, and their pain tolerances. And it tends to go in the direction of a normal healthy control.

Alex X-Health.show: 15:31

So that's the one side of the treatment. And there's also a psychological one. So what's in this psychological part?

Marc Mathys, CNS Therapy: 15:41

Okay, in the psychological part, which is the second hour of a typical double session, you talk to a therapist. The therapist tells you about the pain network. And one way to sort of envision that pain is something like a conference call. You've got some input coming in from your body, you're scared about the pain, you can't do anything, maybe you're guilty, because you can't work anymore, you can't take care of your family. And you're sort of debating whether or not to take that opioid we talked about earlier. And so all these things sort of influence each other. And you stop taking... you don't want to take the drug right away, because you know the medication is bad for you, so you wait, and then the pain gets worse, and then finally you decide to take the medication, maybe it's not working right away, because it takes the time to react, so an hour or two later it's not enough, you take a second pill. That would be typical for a pain patient. We spend time explaining that process. And when, after we've gone through that process, and sort of explained that with the way pain works, and that from a neurotransmitter point of view, you can't maintain the expression of those neurotransmitters, we then go through your life. And we look at persistent stressors, because in our opinion, often the chronic pain is a result of unresolved persistent stress, and the body has to react to it somehow. And so then we give them tools to deal with the persistent stress, an example may be if you've got a boss, and you go to work and your boss does something stupid, and not only does he do something stupid, he does something that affects your work, and so he may make your work worse. You get all upset, why is he doing this, and then you sort of, build up this resistance and this emotional content, and the next day, it happens again, then it happens again, then it happens again. And in that sort of situation, you only have two choices: choice one is to quit the job and find another job, that's very hard to do for financial reasons and other reasons, finding a new job. Or your other choice, which is also hard, is to cognitively restructure your feelings of what happens when the boss says something stupid, and you just say it's basically background noise, I know he's going to do something stupid, he does something stupid every other day, I know it's gonna affect me but generally, I like my colleagues, I generally like my job, I like what I'm doing. And so I'm not going to get all upset every time he does something stupid, because I expect it. Now, we know that if you don't take one of those two options, your pain is not going to change, it's going to remain and it's going to stay to the point where your pain is going to prevent you from working. So you have to actively do one of those two things, both of which are hard. And you can substitute the boss with a spouse, with a kid, with a parent, with social situation, a friend,, maybe with what you're doing in your free time, etc, etc.

Alex X-Health.show: 19:43

So that is something like I've read, like pain behaviors, is that what you just described?

Marc Mathys, CNS Therapy: 19:49

Yes. Typical pain behavior is let's say you're in pain, you come home. And you come home and your spouse is at home and your spouse says to you, why don't you relax, sit on the couch, I'll bring you a cup of tea. And she of course does this, or he, and so now you've had more attention from your spouse than you maybe had in a week. And what's that going to do? It's going to reward the pain. So that's what we call a solicited spouse because they reward the pain. You've got another spouse that takes a completely different result. You come home, you're in pain, your back hurts and the response you get, Look, if you just did some exercise and if you stop being a couch potato all day long and move a little bit, your pain would go away. It's all your fault. We call this the punishing spouse. Again, the punishing spouse also rewards the pain because they're reacting to the pain. So the sort of answer is, you've got to not react to the chronic pain, which is hard to do, that your spouse is feeling. And in fact, we require that the spouses come in for 50% of the sessions, just in order to train the spouse as well as training the patient because the pain is an interaction, or at least partially an interaction in the environment that the patient is in. And it might be a partner, the partner may be a child, whatever, but there's this interaction, which is conditioning, that pain, maintaining it and making it worse,

Alex X-Health.show: 21:34

How not to react to the pain?

Marc Mathys, CNS Therapy: 21:38

It's not easy but the way you not react to the pain is you talk about something else that may be interesting. So your spouse comes home, and is in pain, it's obvious that they're in pain because of the way they're walking, etc, etc. And you talk about the next vacation or you talk about what the kids did, or you talk about anything else other than the pain. You act like it's normal, you don't reward or punish the pain.

Alex X-Health.show: 22:08

That's, I can imagine, is really hard to start. How did you experience it when working with patients? How does it work for them?

Marc Mathys, CNS Therapy: 22:19

It depends on the patient. Some patients at first are very skeptical, they have to learn it, it's not a learning that they're used to. One of the advantages with a stimulation is they see a biological improvement in their numbers, that helps them or tells them to listen to us more. And so that helps the adherence, but it's a new way of dealing with their pain that they're not used to. And it's a way that's not being taught in our society right now. So is it easy? No. For some patients it's easier than others. Most patients have gone through the experience that says that if I ignore the pain, it goes at least partially away. The easiest example is that if you've got somebody that has chronic back pain, and they're a guy and you put a video game into the computer – while they're playing the video game, they won't feel the pain. Now, nothing's been done, the situation is exactly the same. But nevertheless, they're distracted from that pain during that period. The brain is very powerful, it can turn off pain.

Alex X-Health.show: 23:35

So we've already spoken about fibromyalgia. Have you tested the device and actually the combined solution on any other chronic pain patients?

Marc Mathys, CNS Therapy: 23:51

Our clinical studies are on fibromyalgia but we've treated lower back pain, we've treated migraine, we've treated tinnitus, we've treated some other types of pain, irritable bowel syndrome, and that sort of thing. So we've treated a vast variety of pain and all of this pain has a psychosocial component, and can benefit from from the treatment.

Alex X-Health.show: 24:19

Actually I didn't ask yet, how much does the therapy reduce the pain?

Marc Mathys, CNS Therapy: 24:24

Our goal is to eliminate the pain.

Alex X-Health.show: 24:26

Like, completely?

Marc Mathys, CNS Therapy: 24:27

Completely. So our goal with these patients is to eliminate the pain. In our clinical trial that we did, 82% of the patients were pain free at the 12 month follow up. So it doesn't work with all of the patients. But that's our goal.

Alex X-Health.show: 24:44

Could you tell us a bit more about clinical trials results? What did patients say? You said it's, what, five weeks, right? They come every day or...

Marc Mathys, CNS Therapy: 24:56

They come twice a week for two hours. So total of 20 hours in a clinical trial, which is a published RCTs study (Randomized Controlled Trial). 82% of the patients were pain free at the 12 month follow up.

Alex X-Health.show: 25:14

How did you actually got into this? How did you learn about this SET? Actually, we didn't speak about the acronym, right? This Systolic Extinction Training.

Marc Mathys, CNS Therapy: 25:26

Correct, it's called SET – Systolic Extinction Training. I was in Zurich, a friend of mine said, I absolutely should look at this new technology. And so we drove up together to the University of Marburg and I listened to a presentation. And I thought the presentation was absolutely fascinating. And I also thought that it was hard to do. Because you know, medical devices typically is something that you make, and then you ship to a doctor, put it into a hospital, and you're done. This wasn't going to work, because the therapy is a large portion of the treatment, and doctors don't talk to you. They're far too busy. Therapists talk to you but they generally don't use medical devices. So we have to change, you know, hundreds of years of thinking on both sides. The therapists are easier because some of them do do biofeedback and there are some sort of device-oriented therapies. But the idea is to miniaturize this device, put it in the hands of therapists on a sort of per patient leasing basis. So there isn't a big cost to therapists and how the therapists use it in their therapy. Therapists have been treating pain patients for years but generally, they only have about a 30% impact. That is, they help about 30% of the patients. And with the aid of the device, we can dramatically increase that rate. So it's better for the therapists. Many therapists have the idea that pain patients are very difficult, they don't get better, they're needy. They're not the easiest type of patients. We're trying to change all that. One of the other exclusion criteria is our therapy doesn't work if they're high on opioids. So the first thing we do is we get them to the point where they're off the medication.

Alex X-Health.show: 27:45

I don't think we mentioned that, so no meds, no any other pain killers, no, I don't know, canabis. What could you add to those?

Marc Mathys, CNS Therapy: 27:57

I mean, yeah, we don't want them to be high, whether it's alcohol or cannabis, or prescription drugs, or it doesn't really matter. What we're trying to do is sort of reset response mechanisms in the brain. The brain has a pattern, the pattern is chronic pain. We need to reset that within another pattern, a healthier pattern. And the old pattern of chronic pain doesn't go away. But hopefully, we can push it back and replace it with a new active pattern.

Alex X-Health.show: 28:35

Just maybe another question, is there any kind of pain that your device and psychological therapy would not work for?

Marc Mathys, CNS Therapy: 28:45

There are some cases where it's harder or even impossible. One area is if you've got a personality disorder and the pain is a secondary effect to your personality disorder. We find in those cases treating the pain doesn't work very well. What we have to do is or what somebody has to do is first treat the personality disorder, and only then can we come back and solve the pain problem. Another case that is difficult is with episodic pain, certain cancer pains, where there really is very little consistency over time. And we find that also more difficult to deal with.

Alex X-Health.show: 29:35

What I love about what you say, you use the word "difficult". So you're not saying impossible, because, I can imagine, we don't know in the future, what can be developed.

Marc Mathys, CNS Therapy: 29:48

Yeah and it depends on the degree of the psychosocial component, right? If the psychosocial component is very low, then there may not be a lot we can do. If the psychosocial component to the pain is high, then there's a lot that we can do. So some of this is patient-specific.

Alex X-Health.show: 30:09

Why did your friend actually tell you to go to that lecture? What was the point in life that you were at the time?

Marc Mathys, CNS Therapy: 30:17

At the time I was a lawyer. I had been practicing law for many years in California. My friend knew the father of Kati Thieme, who is the doctor that both invented the technology and she's running the department at the University of Marburg, the pain clinic that does the treatment. She had been looking for sponsors. For quite some time she approached the pharma companies, they weren't interested because they're in the business of, unfortunately, selling opioids. That wasn't getting anywhere. And so I looked at it and thought it was interesting.

Alex X-Health.show: 31:01

How did she come up with the idea?

Marc Mathys, CNS Therapy: 31:04

She was on a German Research Foundation trip to the United States at the University of North Carolina and she was just doing general research. The question was, Is there a difference in the EEG brainwaves, in essence, response between healthy controls and chronic pain patients, if they get stimulated with painful stimuli in conjunction with a cardiac cycle? She was just doing general research and her patients came to her and said, You know, I don't know what you did to me, but but my pain is receding. And she said at that point, well, I really don't know what we're doing either, this is just general research. But the effect was so large that UNC immediately patented the approach. And so she went back to the University of Marburg and did a bunch of research, some of which I helped with, which was to figure out why this was working.

Alex X-Health.show: 32:07

[MID-ROLL] This episode is brought to you by the X-Health.show. And me. So if you like this podcast, be generous, hit Follow, leave a review, that will help me invite more such amazing guests for you. Thank you. [MID-ROLL ENDS] That's also the moment when you actually, that's what you told me, you went back to the university, right? You joined the research. Why would you do that?

Marc Mathys, CNS Therapy: 32:32

Well, I gave up my law practice because after you've been a lawyer for a certain amount of time, you find that the clients become a bit the same, they often don't do what you tell them anyway, and you're spending your life solving other people's problems.

Alex X-Health.show: 32:49

What kind of problems were you solving?

Marc Mathys, CNS Therapy: 32:52

At the time I was solving debt problems. In America, 35% of the population either can't or don't pay their bills every month. Typically, they put their head in the sand like an ostrich, and just ignore it. They have credit card debt, they have car debt, they have mortgage debt and these, unlike what the banking industry would tell you, are typically hard-working people, they often have multiple jobs. What happens is, they've been told to sort of use their credit cards, they've been told to live for the day, and then some life event occurs – it may be somebody needing medical care, it may be a divorce, it may be some family member dying – but an event occurs or requires more money. And all of a sudden, you've got somebody that has for years been maintaining their financial status, go underwater, and it's heartbreaking. So I spent a lot of years basically telling them that they don't need a credit card, they don't need all of this debt, paying cash is just fine. And if you don't have the cash in your pocket, don't buy it as a way to get them out. We were able to negotiate with the creditors, we were able to reduce the amount of debt, maybe take them through bankruptcy. Those are the type of things that we did.

Alex X-Health.show: 34:24

And then you dropped that and went back to university?

Marc Mathys, CNS Therapy: 34:28

I looked at this pain stuff, I saw that it was complicated and... Before I was a lawyer, I was an engineer so the engineering side fascinated me. I saw that this expensive lab gear was gonna have to miniaturize to make it accessible. And I also wanted to fundamentally learn what I was doing. And so yeah, I went to the university. For about five years I taught medical students and worked on miniaturizing the device. I mean, on something like this, if you're really going to get into it, you have to understand it and you have to learn it. And as a lawyer, I didn't have the experience, so I needed to change.

Alex X-Health.show: 35:10

What did you teach the students?

Marc Mathys, CNS Therapy: 35:14

We taught them, primarily, the classes called self assertiveness. 35%, roughly, of medical trained doctors leave the professions because of burnout, because they don't like it anymore. And so we tried to...

Alex X-Health.show: 35:30

35% you said?

Marc Mathys, CNS Therapy: 35:31

Yeah.

Alex X-Health.show: 35:31

That's more than 1/3.

Marc Mathys, CNS Therapy: 35:33

1/3 of fully trained doctors leave the profession for lots of reasons, but basically, hospitals are tough places to work in, in all senses of the word. And so we spend a lot of time with the students teaching them that if they're going to help other people, they have to learn to protect themselves and help themselves. And so that was part of the training. The other part of the training is you take an 18-year-old or a 22-year-old or a 26-year-old, that have been basically communicating with other smart people, because we pre-select medical students based on grades, and they've been speaking their peers, and now all of a sudden, you put that person in the situation where they're speaking to somebody at 75 years old that has a chronic and often non-curable disease, and is suffering. This is not something that they're used to and they have to learn how to deal with those patients. We all know that outcomes are a function of adherence, adherence is largely a function of whether or not the patient likes and respects the doctor. So we explain these things to the medical student and run through a bunch of practices and exercises to try to prepare them for the world that they're about ready to enter into.

Alex X-Health.show: 37:00

How did they take that? Because this is something that I heard so many times, actually, that this part is missing at medical schools. So how did they take it?

Marc Mathys, CNS Therapy: 37:12

When these students come to us, some of them take it well, other ones are really skeptical because they focus on the science. They've come to the medical school with this idea that they are scientists, with the idea that they are going to be like Doctor House, with their brilliance they're going to find the solution and the patient is going to walk away happy as a clam. And that's just not realistic. Most diseases, up to 85%, are chronic, you're going to have them for a very long time. And the whole motivational aspect of how you deal with that disease is critical to your health and to your life balance, and to your attitudes, and everything like that, to the whole quality of life issue. Many of the students take the class because they have to take the class and then many years later, when they're on their first job, they realize how valuable it is. We teach them some very precise skills, communication skills, coping skills, we spend a lot of time explaining how stress affects medical outcomes, and give them examples. Those are the type of things that we do. And I think medical schools more and more realize the problem. There are, worldwide, attempts to sort of treat it. I mean, we tell the students that they're caregivers at the end of the day, and many of them haven't even thought of being a doctor means you're a caregiver. For them being a doctor means you're a scientist, and that you're gonna look at cell cultures, and you're gonna look at different bacteria, or whatever it is, genetic mutations, etc, etc. And at the end of the day, if you're working at a hospital, you're a caregiver.

Alex X-Health.show: 39:14

That's exactly what it is. And this is also kind of, you know, stunning. But as you mentioned, if they are accepted at the university based on grades, this means they are already very much into science, all these difficult things. And then, if they were to focus on, how to speak to a patient, it's something different.

Marc Mathys, CNS Therapy: 39:44

Yeah, it's very different. And the real situation is even worse, you know. The medical profession, as does the legal profession, as at the top of corporations, they have a very high psychopathic tendency, much higher than the general population. And that's generally exactly tied in with that many show narcissistic behavior. And so we don't necessarily pre-select the best caregivers. It's a problem with the system.

Alex X-Health.show: 40:15

At the same time we also need them to know all that stuff and to be able to memorize it so, I'm not sure if there's actually any middle or do you?

Marc Mathys, CNS Therapy: 40:28

Yeah, we teach this sort of EBM concepts. Basically, there are three circles and you need to be good at all three circles. One circle is the science and the medical knowledge – everything you learned during medical school. Another circle is what does the patient want? What does the patient desire? And a third circle is what does your intuition say? What does all of your experience say? And you've got to fuse the three circles in order to be a great doctor. You can't be a great doctor if you're missing any one of those three circles.

Alex X-Health.show: 41:10

Sounds pretty right. We want these doctors to be like that. So the University is in Marburg, in Germany near Frankfurt, and we are actually recording in Switzerland, in Delémont. Why here?

Marc Mathys, CNS Therapy: 41:29

The reason is, is because the Basel Area, Switzerland Innovation Park, decided to give us funding and decided to support what we're doing. I moved the company from Germany where it was difficult to find funding, especially for the regulatory aspects, to Switzerland, where we've been strongly supported. There's a nice infrastructure here. Jura, which is the kanton that we're in, has decided sort of strategically to change the watchmaking business into the medical device business. And there's this wonderful Innovation Park, which has been helping us form the company and helping us to drive our mission, which is to bring this technology to patients.

Alex X-Health.show: 42:28

You said, five years in Marburg, so you moved to Marburg from Switzerland, right? Because you were based here, and then you moved back?

Marc Mathys, CNS Therapy: 42:37

No, no I was living in California, I moved to Marburg from California in order to learn about pain. And then I moved to Switzerland, because they provided the environment and the financing to make this a reality.

Alex X-Health.show: 42:54

Okay, and how do you see this startup environment? Or do you take part in startup events here? Or how do we find them like?

Marc Mathys, CNS Therapy: 43:08

They're very good. There's a series of experts in the ecosystem here and subjects are covered such as the IP, such as market access, such as competition, such as patient support, and the regulatory side. We've hired a regulatory person in Switzerland, and we're going through it step by step to prepare all the files, and quality management systems, and everything you need to manufacture a medical device.

Alex X-Health.show: 43:47

Was there anything like, Aha!, the Aha! moment here when you actually started this journey with Basel Area, all this startup environment?

Marc Mathys, CNS Therapy: 44:03

Basel Area, had a pitch competition, we came down, Kati and myself and we pitched to Basel Area and we won the pitch competition. As part of winning the pitch competition, they agreed to fund us. And so we said, okay, good, let's go.

Alex X-Health.show: 44:31

If you won it straight from the university, you were already prepared to be a startup that's pitching for investors or for financing. Did you already go through any, I don't know, startup building programs in Germany?

Marc Mathys, CNS Therapy: 44:53

Even when I was back in California I was advising startups and small companies for many years. I did spend a little while as sort of an in house VC and actually fund companies. So I've been sort of in and out of this startup world for for many years.

Alex X-Health.show: 45:13

At the same time you work on this medical device. How did it change during these five years, and how did it change up until now?

Marc Mathys, CNS Therapy: 45:22

When I came, there was a big psycho-physiological lab, about 500,000 euros had been invested in it and Professor Thieme was treating the patients using that lab. The first thing I did was an interim step, I reduced the lab to where it was about 70,000–that's where we sold it to a hospital. And now I'm in a third step, in which I want to reduce that lab to, to where it can be sold for about 20,000. So that's the goal.

Alex X-Health.show: 45:57

Awesome. Okay. And could you actually tell us a bit more about Professor Thieme? I saw a couple of videos with her, she seems like so gentle on one side, and on the other side, she knows so much. I mean, the number of papers she published, let's just say that there's so many of them. How did that collaboration look from your side?

Marc Mathys, CNS Therapy: 46:27

She is incredible. I mean, it's incredible based on what she invented, what's also incredible is the empathy that she shows to the students. And with pain patients, if you're a therapist, when you go through therapy school, many of the therapists end up dealing with psychiatric patients. With psychiatric patients – they're fundamentally mentally sick, most of them. And so as a therapist, you have to protect yourself, you have to psychologically protect yourself from them. If you're treating a pain patient, it's a very different group of patients. First of all, they aren't mentally sick. And secondly, you have to show empathy, and you have to think with them, because that's the way you're going to cause them to change their behavior.

Alex X-Health.show: 47:26

What do you mean, "think with them"?

Marc Mathys, CNS Therapy: 47:28

You have to understand them, you have to put yourself in their shoes. And with a pain patient, if they do tomorrow, what they did yesterday, and what they did for the past five years, tomorrow in the next five years is going to look exactly the same. So in order to treat a pain patient, you'll have to induce behavioral change. We are hesitant to change our behaviors: a) it's hard to do with as we're fighting brain patterns, we're scared of the results, etc, etc. And you only change your behaviors, if you can trust the person that's telling you to change your behavior. So you have to build up that level of trust, that level of understanding, the whole idea that this therapist that I'm talking to understands who I am and where I'm coming from. And Professor Thieme is very good at that.

Alex X-Health.show: 48:29

But this... I'm just thinking aloud that this might be actually also one of the challenges for you because you're not only selling the device, you need to sell it to the right people.

Marc Mathys, CNS Therapy: 48:41

Yes. And so we're addressing that in a couple of ways. One way is, we're only going to sell to people that we've certified, so we know that we have a feeling that they know what they're doing. Secondly, we build up an e-learning program, which basically choreographs these therapy sessions session by session that both the therapists and the patients have access to it. The information is different depending on on who you are. And then finally, there are groups of therapists or maybe chiropractors or maybe physical therapists, that have spent a lot of time working with patients that have orthopedic problems, and they know that the motivation is a huge factor. And these are the type of patients or the type of therapists, or the type of practitioners that we're looking for because they realize that it's all about adherence, and they realize that it's all about changing behaviors.

Alex X-Health.show: 49:45

There's one thing I forgot actually to mention that please don't take, guys listening, whatever we say, it's not medical advice. We are not doctors, so please don't take it as a medical advice. I mean, you're a lawyer, right?

Marc Mathys, CNS Therapy: 49:58

Yeah, absolutely. I'm a lawyer, and maybe an engineer, but I'm definitely not a therapist and I'm definitely not a doctor.

Alex X-Health.show: 50:06

This is just a reminder. But now, it is still not available on the market, right? Not available for the patients? Or is it a bit available for the patients? What is the situation?

Marc Mathys, CNS Therapy: 50:20

We're in a highly regulated, and probably thankfully so, world and so in order for us to sell it, we have to go either through MDR, FDA, and it needs to be certified as a medical device. We have not done that yet. We're operating under a university ethics opinion. And so the only two places to get treated are at the University of Marburg pain clinic. And we also have a spinal cord hospital, where we treat paraplegics in Bald Wildungen, in Germany. So those are the only two places

Alex X-Health.show: 51:01

And paraplegics – is this phantom pains? Or what do you treat there?

Marc Mathys, CNS Therapy: 51:07

The focus is not phantom pain, that's often resolved, but paraplegics have a large portion of their body that's not working. That means that the regulatory system is under more stress. And 85% of of paraplegic patients have chronic pains, so it's a very large percentage. And we find that the stimulation helps them. Sometimes it needs to be maintained, where we're sort of stimulating them on a weekly basis. But stimulation helps the regulatory process.

Alex X-Health.show: 51:49

You said before that Professor Thieme was looking for a way to bring it to the market. How did you secure investor for this project?

Marc Mathys, CNS Therapy: 52:02

Most of the investment has come from the German Research Foundation, which thankfully, has helped us and that's what's funding to the University of Marburg. Since I became involved, I managed to find the German investor that was able to give us some funding, which is financing a lot of this regulatory process that we're going through right now. Funding for a medical startup is not always easy.

Alex X-Health.show: 52:32

What's the plan to bring it to the market?

Marc Mathys, CNS Therapy: 52:34

The plan to bring it to market is first complete both the FDA and the CEE approvals, and then it's to give it to therapists and get them to go ahead and treat patients. We have a five-year waiting list at the University of Marburg right now just based on a couple of news videos that were done. So I think finding patience is not a problem. And the therapists seemed quite receptive to what we're doing, too. So I think it's a question of going through the approval process and getting device in the hands of people,

Alex X-Health.show: 53:14

Any timeline you have in mind, any geographics?

Marc Mathys, CNS Therapy: 53:18

I wish it was yesterday. So I hope to have FDA approval inside a year. From a geographic point of view, the US right now is easier from a regulatory point of view, we'll probably going to go to Los Angeles to some of the clinics there that specialize in substance abuse cases, with celebrities and that sort of stuff. So we can get some celebrity support just by treating them?

Alex X-Health.show: 53:49

Why why substance abuse clinics?

Marc Mathys, CNS Therapy: 53:52

Because these patients come in the substance abuse clinics and they're in pain. They're either in emotional pain or they're in physical pain, or both. And they're also high on drugs. And so we think that we can help those patients get off their pain and get off those drugs. And from the clinic point of view, they charge a lot of money per day to the celebrities, the success rates are very low. And they're looking for a way to differentiate themselves, compared to the clinic next door, and we can help with that process. That's the thinking.

Alex X-Health.show: 54:36

Can you also help in drug addiction? Is that what you're saying?

Marc Mathys, CNS Therapy: 54:41

Yes, we haven't proved it yet, I don't have a clinical trial on it. But if you've got somebody that's high on opioids, what we do is we stimulate them every day and we generally reduce the opioid level. We've done that on a few test cases and it seems to have worked, but it's not easy. And, you know, drug abuse patients have relapses and they're not particularly honest with you. And so you've got that whole host of issues.

Alex X-Health.show: 55:15

Speaking about that, what what are the biggest challenges now? Or what could go wrong in this bring the product to the market plan?

Marc Mathys, CNS Therapy: 55:23

I don't think too much will go wrong. I think it's just more a question of how successful will be we be in bringing up therapists and bringing up patients, and replicating the results that we've had at the University of Marburg. I think those are the unknowns. Of course, there are challenges. But our challenge is bringing this to a lot of people in a sustainable fashion,

Alex X-Health.show: 55:54

What do you need to secure or what kind of support you need, or what kind of fuel to drive this?

Marc Mathys, CNS Therapy: 56:05

We're okay with money right now, thankfully. What I'm looking for is a hospital, or a clinic, or something outside of Germany, where we could go in and we could replicate the German results. Because today with medicine you get to replicate what you're doing in a different geography, with a different group of people. And so just from a prove the science point of view, that's really our next step is a clinical trial in a completely different location.

Alex X-Health.show: 56:43

We spoke about immediate steps, what do you need now, is there any broader picture that you could speak about? Where do you see this device plus psychological training in the future?

Marc Mathys, CNS Therapy: 56:58

The broader picture is to get this in the hands of a large number of pain practitioners. Be they physical therapists or psychological therapists, or chiropractors, or other people and have them use it. I mean, take average chiropractor, they have a whole business where they basically manipulate backs and manipulate parts of the body. And that's good for a certain set of patients, but a fibromyalgia patient complaining of pain – back manipulation is not going to help that patient. So we give them a tool and a method to help a group of patients that they can't help right now.

Alex X-Health.show: 57:46

Can they also help on the psychological side? Will you also give that training?

Marc Mathys, CNS Therapy: 57:52

Yeah, we have to. On the one hand, we do it from the learning point of view. But if you've been a pain practitioner for several years, it doesn't matter what you're doing, you realize very quickly, that the motivational and the emotional, and the conditioning aspects of pain are just crucial. You have the experience from seeing patients, so they know this.

Alex X-Health.show: 58:20

Marc, thank you very much for this highly interesting conversation about pain and the pain mechanisms. And actually, you know, the idea of getting rid of the pain, it's mind blowing. So thanks for sharing that. And you guys if you want to see where CNS Therapy is now, what point, if they're available in your country, please go to CNStherapy.com. Thanks again.

Marc Mathys, CNS Therapy: 58:56

Thank you so much for the interview.

Alex X-Health.show: 58:58

I'm totally impressed by the audacity of researchers turned startup founders, doctors turrned entrepreneurs or ordinary parents turned healthcare innovators. People battling the battles that no one fought before. For the eXtra health of the future. So if you see a startup posting on LinkedIn, show them some love, hit Like, comment, That's fabulous! If you have a couple of drops more of that altruism, follow the X-Health.show, leave a review here. I'll be able to bring more of these visionaries to you. So a big thank you. You're awesome. See you next week.

SPEAKER: 59:30

The information in this podcast is for informational purposes only and should not be considered medical advice. If you have any medical questions, please consult your healthcare practitioner. The opinions on the show are Alex's or her guests. The podcast does not make any responsibility or warranties about guest statements or credibility. While the podcast makes every effort to ensure that the information shared is accurate, please let us know if you have any comments, suggestions or corrections.