Good Life Project - How To Heal Injury, Illness & Disease with Regenerative Medicine | Dr. Adeel Khan

Episode Date: May 23, 2024

Could regenerative medicine transform how we treat disease and even reverse aging? Dr. Adeel Khan shares groundbreaking insights on leveraging stem cells, gene editing, and tissue engineering to unloc...k healthcare's full potential. Learn how induced pluripotent stem cells are being used to regrow neurons in Parkinson's patients' brains. Hear about revolutionary gene therapies that could permanently alter genetics to cure chronic illnesses. Discover the incredible possibilities emerging at the intersection of cellular medicine, CRISPR, and 3D-printed organs. But also gain wisdom for navigating this complex landscape responsibly. Dr. Khan provides an accessible primer on the risks, limitations, and realistic timeline for bringing these powerful technologies into standard practice. The future of medicine has arrived - tune in to stay at the cutting edge of what will soon be possible.You can find Adeel at: Website | Instagram | Episode TranscriptIf you LOVED this episode you’ll also love the conversations we had with Dr. Frank Lipman about the 6 pillars of well-being.Check out our offerings & partners: Join My New Writing Project: Awake at the WheelVisit Our Sponsor Page For Great Resources & Discount Codes Hosted on Acast. See acast.com/privacy for more information.

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Starting point is 00:00:00 The holy grail of regenerative medicine is basically this intersection between cell therapy, gene editing or gene therapy and tissue engineering. So all three of those is kind of what's the next era of medicine. And combining all three of those in a very sophisticated way is what's going to allow us to regrow organs and fix any disease known to man, I think, especially once CRISPR becomes a reality, you should be able to fix any genetic defect. We're getting there. We're not there yet, but I think that's going to definitely happen as these technologies continue to evolve. So I have to tell you, the conversation I'm about to share kind of blew my mind in the best of ways. What if you could regrow damaged tissue,
Starting point is 00:00:40 reverse chronic illness, cure neurodegenerative disease, even slow aging by harnessing the power of your own body and cells. It may sound like science fiction, but incredible breakthroughs in the emerging field of regenerative medicine are making this a reality. And at the same time, the hype machine here is on overdrive. So I wanted to sit down with a true visionary in the field to understand what's real, what's not, and where we're headed. My guest today is Dr. Adil Khan, a visionary leader in this exciting new domain of regenerative healthcare. And as a physician scientist on the cutting edge of cellular therapies, he is really pioneering treatments that are transforming lives. In this conversation, you'll discover how things like stem cells, gene editing, PRP, prolotherapy, and tissue engineering are converging to create powerful new ways of repairing the body that just a generation ago seemed like the stuff of fantasy.
Starting point is 00:01:34 And Adil shares insights from the front lines of developing these game-changing technologies along with the profound results that he's achieving with patients with everything from neurodegenerative conditions to muscle loss. Yet he's also really candid about the current limitations and risks, stressing the importance of rigorous science and safety alongside the incredible promise. And we do a lot of myth busting about some of the rampant claims about regenerative medicine interventions. Talk about what's real, what's hype, what is coming down the pike. And his passion for democratizing access really shines through along with just this grand vision for the future
Starting point is 00:02:10 integration of cellular medicine. So get ready to have your mind pretty much melted the way mine was when it comes to what may be possible in healthcare from regenerating organs to reversing chronic disease, curing illness, and reversing aging altogether, but also gain deeper wisdom for navigating this emerging landscape responsibly as a patient today so you know what to ask. Adeel's balanced perspective and wealth of knowledge really provides the perfect primer to this most hopeful and hyped field of medicine. So excited to share this conversation with you. I'm Jonathan Fields, and this is Good Life Project. The Apple Watch Series 10 is here.
Starting point is 00:02:57 It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch, getting you eight hours of charge in just 15 minutes. The Apple Watch Series X, available for the first time in glossy jet-black aluminum.
Starting point is 00:03:17 Compared to previous generations, iPhone Xs are later required. Charge time and actual results will vary. Mayday, mayday. We've been compromised. The pilot's a hitman. I knew you were going to be fun. January 24th. Tell me how to fly this thing. Mark Wahlberg. You know what the difference between me and you is? You're going to die. Don't shoot him. We need him. Y'all need a pilot. Flight risk.
Starting point is 00:03:42 I think medicine is in such an interesting state right now. A lot of people are railing against different elements of medicine, healthcare systems, stuff like that. And then we see this field of regenerative medicine sort of emerging almost like out of the ether, like in the mode of a savior. And I feel like there's a lot of hope and there's a lot of hype. And I want to go into a bit of that with you. And then I'd love to dive into some of the specific modalities that are getting a lot
Starting point is 00:04:11 of attention and really talk about them and what the future holds. But when we use the phrase regenerative medicine these days, just more broadly, what are we actually talking about here? Yeah, at a very basic level, the best way to understand it is we're just trying to repair or fix tissue back to the way it was. So instead of cutting things out. So for example, if you have a bad knee, right now, they may take it out and they'll put in a new knee, artificial one. But imagine if we can grow you a new knee, so to speak, or grow you some new cartilage. So that's the idea or promise of regenerative medicine.
Starting point is 00:04:47 Obviously, this concept has been around for decades, but we're finally, as Arnold Kaplan put it, who's a kind of pioneer scientist in regenerative medicine, that we're at the beginning of the end, so to speak. Meaning the end of just like the scientific discovery area. And now we're actually beginning the actual clinical translation of just like the scientific discovery area. And now we're actually beginning the actual clinical translation of everything that the last 30 years of science has taught us. So is it possible that things like knee replacements or like a lot of what's orthopedic surgery today in 10, 20, 30, 40 years, we'll kind of look back at that and say,
Starting point is 00:05:22 how on earth did we ever allow that to happen? Oh, there's so many. I think in 30 years, I think we'll look back and we'll be like, wow, I can't believe this is how medicine used to be. From all chronic diseases, not just orthopedic, but all cardiovascular disease, COPD, psoriasis, inflammatory conditions, even cancer is going to look very archaic in 30 years from now because right now it's just a nuclear approach which is just kill all your cells in the body including the good ones with chemotherapy and eventually it's going to be designer cells that i believe will be the solution to a lot of these as we've already seen and this is stuff that's already happening now and it's only getting more sophisticated as time goes on.
Starting point is 00:06:05 So it's not something that's 50 years down the road. It's already kind of happening in practice. And I'm obviously treating patients already with a lot of these technologies. And the results are only getting better every year because the technology keeps getting better. Yeah. I'm curious, just on a personal level, when you decide I'm going to enter the field of medicine, did you know from those early days, oh, this is the particular branch that I want to go anything like that. And so it was more almost out of frustration of not being able to help people the way I wanted
Starting point is 00:06:50 to help them, especially because I started out as a sports doctor and a family doctor and in primary care medicine and sports medicine, it's traditional medicines quite not only mundane, but it's a lot of patients don't get better. And the options are basically just cortisone injection. If you have pain, physiotherapy, acupuncture, shockwave, you know, some stuff like that. And if that doesn't work, then they send you off to surgery. And a lot of times patients don't want surgery. And sometimes surgery is risky or dangerous, or they can't even do surgery. So then you have patients with chronic pain who are living with it and suffering, and there's no one to help them. And that's really got me into it because chronic pain is not an easy field in general, but it's also one of those things that
Starting point is 00:07:34 affects more than just quality of life. Because as we probably all know now, longevity is highly correlated with movement and exercise and putting on muscle. But if you're in chronic pain, you can't really exercise. You can't move properly. You can't load the muscles the way you want. So your health deteriorates. And then chronic pain is also associated with mental health issues, depression. A lot of times chronic pain patients have history of trauma. And so there's all these other factors that interplay into it as well. And that was my big driving force is kind of just helping these people that no one else seemed to want to help. And then I just started helping them and at which project out of medicine, and it just kind of went from there. Yeah. I mean, I'm curious also,
Starting point is 00:08:11 because when you make this sort of like left turn, like you're doing this thing, you're using all the traditional modalities, you're sort of like following standard of care that has been standard of care for generations at this point. Right. And you're doing the thing and you're like, okay, so sometimes it's working, but oftentimes it's not. And then you advance to the next level and that thing sometimes it works. I mean, I think we've probably all heard countless stories that maybe folks listening in
Starting point is 00:08:33 have proceeded all the way through surgery and then gotten through that and gone through the rehab and then they're still actually not better. And I can't imagine the futility that sets in when you figure like, okay, I've done all the things. I've checked all the boxes. I paid all the money. I've endured all the suffering and the added pain and the recovery, and I'm still not feeling better. On an individual level, that can be brutalizing. And I imagine for a physician, that's also got to be psychologically kind of brutalizing. It is. And that's actually why most physicians are burnt out. It's not because job satisfaction
Starting point is 00:09:09 is highly correlated with your ability to help your patients, because that's why we become doctors. We want to help people at a very fundamental level, most doctors. And so if you can't see your patients get better, it becomes very frustrating and you start getting burnt out. And a lot of doctors are burnt out because they're working in a broken system and they're not able to provide meaningful solutions to their patients. It's just a revolving door or it's just kind of a band-aid solutions. And there are obviously traumas and stuff like that where surgery is needed and you have to get surgery.
Starting point is 00:09:43 But there's by far the vast majority of the reason our healthcare system is breaking down is exacerbation of chronic conditions and increase in chronic diseases. And we know these things are majority preventable with lifestyle. Over 80% has been the statistic that's already published. So why don't people change? And then there's so many other issues on that. So I think we're kind of almost past that point where I'm kind of like, okay, people are going to be people are it's also because our environment is set up for failure. It's so hard to live a healthy lifestyle when we have an obesogenic environment with toxins, foods, everything that that shouldn't be approved in the food chain is approved. And, and so it's just all
Starting point is 00:10:24 these other factors that make living a healthy lifestyle really challenging. But regenerative medicine has the ability to increase your physiology and your resiliency so you can deal with the modern environment and you can live a healthy lifestyle easier. And that's, to me, is the most impactful thing about what we can do for a lot of people.
Starting point is 00:10:43 Yeah, I mean, that sounds very cool. So when you make this decision and you're like, all right, this isn't the path for me. I want to take this other path. And like you described, you didn't get any training in this in med school. I'm curious, how do you actually go about saying, I need to actually understand what this is and get trained and competent on a level where I feel like I can turn around and offer this to patients? Yeah. I guess it's like that quote where it's like, everyone goes left and then you go right. And then you're kind of left on your own trail and trying to figure it out. So that's what I did. And I was fortunate because there's a doctor in Canada, Dr. Anthony Gallia, who was kind of a pioneer in platelet
Starting point is 00:11:18 rich plasma injections, which is older technology now, but something that was used quite a bit in regenerative medicine for muscle tears and tendon tears. So a lot of athletes were doing it. And so I got fortunate to work with him on that regard. And I learned a lot, but then I traveled, traveling into Asia, traveling into Europe, Middle East, and all these other places where, hey, guess what? They've been using regenerative medicine a long time. And especially in Japan, which is probably the birthplace of cellular reprogramming and all this genetic modification to cells and kind of the holy grail of regenerative medicine, really, which is making an old cell young again, the Yamanaka factors that was birthed in Japan. And so that alone made me very curious about Japanese culture
Starting point is 00:12:03 and everything. And so when I worked there, I learned a ton. And then just kind of shadowing different doctors and learning and then putting it all together. Because instead of looking at the body in a siloed approach, which is still what most doctors do with chronic disease, there's more similarities than there are differences between chronic illness. There's something called 12 hallmarks of aging. And if you look at them, they tend to repeat themselves with not just aging, but with heart disease, with neurodegenerative conditions, with cancer, with osteoarthritis, it's all the same root cellular dysfunctional patterns that drive the illness. And so once you start seeing themes and patterns and repetition, then you put the pieces together. And I guess I managed to put the pieces together, I think, before a lot of other people did, maybe. Then that's why
Starting point is 00:12:47 I've been able to be very fortunate in helping some patients that no one else has been able to help. And then you get a reputation for helping these patients that no one else can help. And word spreads pretty quickly, especially amongst the communities that I'm working with, you know, celebrities and high net worth people and stuff like that. Yeah. I want to dive into some of the different modalities and get even a little bit into the weeds with you, because I think each one, there are a lot of questions people have probably heard about them. Like, are they real? Are they not? Were they for the way not for? So you just brought up one that I think is probably the one that a lot of people hear
Starting point is 00:13:19 about and talk about commonly shorthanded often as PRP, platelet-rich plasma. What are we actually talking about? What is that? Yeah, I like what you said at the beginning of the talk, which was hope or hype. And that's really the biggest problem with regenerative medicine still is the lack of standardization and the amount of, unfortunately, charlatans and predatory doctors who are claiming they're regenerative medicine experts and don't really know much and are just trying to make a quick buck off a patient. With that said, and that's a big problem with PRP, so platelet-rich plasma is where we take your blood, we centrifuge it, and when you spin it real fast, it separates into different layers. And the plasma kind of sits on top and you can
Starting point is 00:13:58 isolate that because when you centrifuge it, it concentrates the platelets, hence the name platelet-rich because it's rich in platelets, hence the name platelet rich, because it's rich in platelets. And those platelets actually release growth factors and signals to reduce inflammation and promote regeneration. So they send signals to repair tissue. But those signals are relatively weak. So they don't work for many conditions. They work for really only muscle tears or tendon tears and usually not chronic degenerative stuff, but more acute is really where it shines. And even then the problem is, again, is lack of standardization. There's different types of PRP. If you don't get the right type,
Starting point is 00:14:35 then it may not work even for a tear. So you have to be careful. You really have to go to someone who kind of understands there's a nuance even with PRP. And it has to be because if you use the wrong type of PRP, it can actually make things worse. And the same thing with any of these technologies. So you have to understand the science and not just be a clinician. And that's the tricky part about this field. And regenerative medicine is very dense in that way. It's not just being a doctor in the sense you're just injecting people or being a surgeon with your hands or mechanics. You also have to understand the science and basic science. And a lot of that is traumatizing to doctors because
Starting point is 00:15:08 they have to memorize all these pathways in medical school and they just want to forget about them and they don't want to review that stuff at all. So I enjoy that stuff for whatever reason. So I find it fascinating and I am an interventional doctor now. And so I obviously inject people and treat them all the time with my hands, but I'm also reading all the time because I have to understand the science. Yeah. And it sounds like it's the type of field also where the science is just changing and emerging and there are new things being discovered, you know, like almost on a daily basis. But it's interesting that one of the knocks that I've heard on PRP is that I'll talk to 10 different people who've gone to 10 different doctors and had PRP treatments for, you know, like, let's say a similar condition, a knee injury or a tendon injury. And some will
Starting point is 00:15:49 say it literally changed my life. It stopped me from having surgery. It healed everything. I'm pain-free. And others will walk around and basically say like, nothing, like there's literally, it had zero effect. Is that more about some things just aren't responsive or some people aren't responsive? Or is it more about not properly matching the modality? That's exactly what it is. Most doctors, unfortunately, regenerate medicine because it is a relatively nascent field. Unless you've gone through the progression and you have a lot of experience. Because a lot of people dabble in it, especially surgeons're good surgeons are great at cutting people but they're not very
Starting point is 00:16:28 good at injection and they're not very good at basic science that's for sure and so it's a lot of times they're trying to do something but they don't fully understand all the nuances behind it and that's why you get all these mixed results because prp probably shouldn't have been offered to that patient in the first place if it was not the right indication and the right patient. And there's a lot of factors. Of course, there's going to be cases where you think it should have worked, but it didn't. And then you should have other tools, hopefully in your toolbox to help that patient. But a lot of times doctors don't because they don't understand that there's a progression in how you can kind of approach patients and use different modalities.
Starting point is 00:17:09 And basically, I think it's more just matching the right modality with the right patient. I think that's really what it comes down to. And that's where I feel fortunate just because I've had patients from all over the world in some of the most complex cases. I've been able to, obviously, it's not like I got here overnight. I had to kind of experiment a little bit and try different things on different patients and figure out what works, what doesn't, what are patterns. And there's a lot of that. And now we're trying to do it in more formal settings where we're doing various clinical trials and to really show the efficacy of what we're doing in real life. Yeah. Are you doing clinical trials with PRP right now or focusing more elsewhere?
Starting point is 00:17:39 More on stem cells. So we're doing a clinical trial with stem cells and osteoarthritis right now and then gene therapy as well. Very cool. You know, one of the curiosities as you're talking also is, and I've seen this, I've had some experience with regenerative medicine myself. And one of the things that surprised me right away is, you know, you'll often walk into an office with, you know, either x-rays or, you know, like an MRI or typical scans. And then you're sat down and somebody says, well, that's nice, but I'm going to actually do a completely different type of diagnostic on you.
Starting point is 00:18:12 And very often like the default is some sort of super high power ultrasound, which I had always sort of like looked at as, well, that's the quote lesser way. Like that's the lesser tool to do diagnostic, but it seems like ultrasound is really a central tool in a lot of the diagnostic side of regenerative. Was that just my experience or is that pretty common? No, it's completely true for, especially for musculoskeletal, like joint, muscle, tendon, nerves, that type of stuff. Ultrasound, dynamic ultrasound, especially is often more accurate than MRIs, but it depends on the user. And that's the biggest issue because MRI, you can just go into a machine and anyone can do it. But ultrasound is so dependent on the probe and how you hold it and all these other little finicky things. So that finesse of
Starting point is 00:18:52 ultrasound skills is very rare, actually. So you must have gone to a good physician if they knew how to use it properly. Yeah. What's the difference between dynamic and sort of the regular? Meaning they get you to do actual movements or they'll get you to like move your shoulder, do different positions because an MRI is static. Right. You can only be in one position really, right? And that's why standing MRIs are becoming more popular too, because then you can see stuff that you can't always see in the laying position.
Starting point is 00:19:16 That makes a lot of sense. So on the hype side of PRP, well, I guess what you're saying is when people talk about PRP, you're really looking at soft tissue injuries probably around joints is really the prime reason. Yeah. It's not good for chronic degenerative stuff. And I find it sad when I see patients spend money and get told that it may help with this, but in reality it wouldn't have helped. And then the doctor's just like, yeah, it's 50, 50. It may work. It may not. And the patient's just like, yeah, I'll try it then. And, but they should just, they just don't have the understanding to say like, no, this is very unlikely to work. We should try something else. And I'm very honest with my patients. And I'd rather them not do anything at all than do
Starting point is 00:19:54 something that doesn't have a high chance of success. That's my personal take on patients, but not everyone's like that. But PRP is not great for degenerative processes. And a lot of patients are living with degenerative conditions and And a lot of patients are living with degenerative conditions and looking for support in those regards. Yeah. And we'll be right back after a word from our sponsors. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist whether you're running, swimming, or sleeping. And it's the fastest
Starting point is 00:20:30 charging Apple Watch, getting you 8 hours of charge in just 15 minutes. The Apple Watch Series X. Available for the first time in glossy jet black aluminum. Compared to previous generations, iPhone Xs are later required. Charge time and actual results will vary.
Starting point is 00:20:46 Mayday, mayday. We've been compromised. The pilot's a hitman. I knew you were going to be fun. January 24th. Tell me how to fly this thing. Mark Wahlberg. You know what the difference between me and you is?
Starting point is 00:20:56 You're going to die. Don't shoot him. We need him. Y'all need a pilot. Flight risk. So one of the other things I've seen PRP, and this feels like it falls on the hype side based on what you're saying, is for hair regrowth or hair stimulation. I am definitely in a camp where I don't have a lot of hair left, but I haven't gone down that road myself at all. I'm not interested.
Starting point is 00:21:21 But I've seen it promoted that way in a lot of different ways. Real or hype? Yeah, no, it's definitely more hype than real. So it can help in select cases. If you, it's very, I would say hit or miss. And I've tried it myself personally. And I mean, I have good hair now, but not because of PRP, but because I've seen many other patients do it too. And it tends to be so hit or miss. And I just don't recommend it anymore personally, because I just don't know if it'll actually work. And most of the time it doesn't, it feels like, because it's just not strong enough. The signal for regeneration and for what you're trying to do and achieve is not going to be
Starting point is 00:21:55 there. And there's just better technology now. So I personally wouldn't recommend it for that. Got it. Okay. If somebody is exploring PRP, what are a couple of good questions that they might ask or ask a physician to sort of like see is, is this person right for me? And is this modality right for me? Yeah, I think if you should ask what type of PRP is it? And do you
Starting point is 00:22:16 have different types of PRP? Because most physicians don't, but those sophisticated ones, which are a handful in the US, do have different types of PRP and understand the nuance behind the different types. So that right away will give you insight that this physician really knows what they're doing. And then the other big thing is, as you said, was ultrasound guidance. Because there are many doctors, especially surgeons, who think they can inject into a joint or a tendon without ultrasound, but they can't. There's been studies showing this. An experienced orthopedic surgeon still injects into the wrong spot in the knee joint injection 20% of the time. It goes into the fat pad instead of going into the joint. So it does not matter who you are. You can't just
Starting point is 00:22:57 palpate. This is modern era. You need to use image guidance. And the problem is it's a steep learning curve. It's not an easy thing to use ultrasound. So a lot of doctors just don't want to learn. That's PRP. I want to talk about one other modality before we dive into what I think will be a richer conversation around stem cells and potentially even gene editing. But there's one other modality that I'm familiar with is prolotherapy, which seems like maybe that's actually the oldest modality of all of this. It is, yeah. It's been around since the 60s, yeah. Yeah. So what is that? What do we use it for? What do we not use it for? Yeah. The principle of that was basically using, well, it's really just dextrose and saline, which is just sugar water, essentially.
Starting point is 00:23:38 And the reason they use sugar water was to just, I think they were just experimenting with different things. And they found that when they looked at how it affected the ligaments, it caused proliferation, which means it's stimulating inflammation and helping things to become stronger. So you don't want to promote inflammation in certain areas. For example, in the joint, you definitely wouldn't want to be doing prolotherapy just from a scientific level, although there are still people doing it. But again, I don't think they understand the principles of what you're trying to achieve. If you're trying to achieve a pro-inflammatory response, you want to do that generally for a muscle tear, or you want to do that for ligament instability. So if the ligaments aren't stable,
Starting point is 00:24:17 for example, we have patients with Ehlers-Danlos syndrome who have severe ligament instability, and that's where we do prolotherapy. And we use, we may use a mixture. Dextrose and saline is a very old technology. It still works, but you may have to do like six, seven, eight sessions. What we use personally is we use something called bone marrow aspirate. And then we use something called copper peptide. And these help to stimulate collagen production and proliferation, and they're much stronger and much more potent. And I find people only need one procedure with it oh that's so interesting yeah because i've always heard about it in the context of anywhere from like three to ten like in a series or something like that but but it sounds like it's that's because it's using
Starting point is 00:24:56 an older technology basically exactly yeah and it makes sense that that wouldn't be because if that's actually encouraging inflammation i guess because that then becomes a signal for the body to send blood and nutrients to an area to try and like actually heal what wasn't healing. Yeah. Then you wouldn't want to do that in an area that was already inflamed. Exactly. Which is why PRP, if you use something called leukocyte rich PRP or there's PRP can come in two colors and it can be golden or it can be red. So the red PRP is generally not that advantageous for most things, unless it's just a chronic muscle tear. But a lot of doctors don't understand the difference and they'll put red PRP into a joint, but that's pro-inflammatory.
Starting point is 00:25:35 So you're actually potentially making the patient worse, which I've seen. Got it. Let's talk about the area that I think is getting just so much attention. I would imagine you're spending a lot of time. Well, it sounds like you're already running trials in, which is stem cells, because I think this is a bigger, more complex topic. So let's start with a basic question. When we're talking about stem cells, what are we actually talking about?
Starting point is 00:26:00 I think the best way to explain stem cells is an analogy. And so imagine your body is like a city. You have the central library where all the information is to tell your body on the instructions on what to do. And that central library, think of it as your nucleus where the DNA is. Those are the instructions. And then you have the mitochondria, which is like a nuclear power plant. And then you have all these different districts and cities the mitochondria, which is like a nuclear power plant. And then you have all these different districts and cities in your body, which is like the organ systems. And then over time, what happens is the library starts becoming damaged, like the books and the
Starting point is 00:26:37 instructions start becoming wrong as they replicate because your cells are always undergoing replication. But then you have these little repair guys who come in there and fix things. Those are the stem cells. Their job is to come and repair DNA damage, to repair damaged tissue. And they're kind of these cool little architects, but also construction workers at the same time. And they're able to figure out how to fix things when they go wrong. But unfortunately, over time, the library starts getting too much damage, and the books start getting more and more damage damage and the repair guys can't keep up. And then this is what's called genotoxicity or DNA damage. And this is what leads to aging when your DNA repair isn't the way it was when you were younger.
Starting point is 00:27:18 And to put that in context, when you're a child or a baby, you have 200 stem cells per one cell. And then by the time you're 80, you have one stem cell per cell. So it's gone down by an order of, yeah, 200 basically, right? It's order of magnitude. So it's quite a bit different. So that means the stem cell decrease in function and number, it's called stem cell exhaustion, is one of the most important hallmarks of aging. And that's why stem cells are such a hot area of research, not just because of their applicability to chronic pain and all this stuff, but aging and longevity is one of the hottest topics right now. And so many people want to learn how can they live longer and healthier and better lives. And
Starting point is 00:28:00 this potential is obviously in stem cells, because once you understand why we age, you can understand why stem cells have so much potential. Got it. So if these are so powerful, when we talk about using stem cells in regenerative medicine context, then take me deeper into that. Yeah, the biggest issue with stem cells and similar to PRP is lack of standardization. So there's so many different type of stem cells and similar to PRP is lack of standardization. So there's so many different types of stem cells. And the word itself is almost meaningless because are we talking about a mesenchymal stem cell or hematopedic or induced pluripotent stem cell? There's all these different
Starting point is 00:28:34 types. But the most important thing to understand is how do we control the stem cell to do what we want? Meaning how do we almost program it in a way so that it sends the signals that we want it to send. And that's called cellular engineering. And that's kind of the era we're living in now. Whereas before we were kind of just taking stem cells from your body or from an umbilical cord, and then we were just injecting them back in. And the results have been very mixed for that. And they continue to be because there's no standardization. And so although we still use um's no standardization. And so, although we still use umbilical cord stem cells in practice, we have now engineered stem cells
Starting point is 00:29:10 and engineered products that we're using because we know better how they're going to function once you put them in the body. And it allows for better standardization. This is kind of where we're headed now. And when I mentioned earlier about that Japanese fellow, Yamanaka, pressing the reset button on an old cell and making it young again, that's called induced pluripotent stem cell or IPSC. And those IPSCs are kind of the holy grail of stem cells because they can turn into any type of tissue in your body and they have the ability to actually engraft, which means they can actually regrow new tissue. And they have the ability to actually engraft, which means they can actually regrow new tissue. And this has been shown in clinical trials with Parkinson's disease,
Starting point is 00:29:49 with diabetes. And now there's so much research happening for so many different organs. And the sky's the limit, right? If you can grow any type of cell and repair the body, then you can theoretically eventually fix any degenerative condition in the body. And even aging eventually, I i think maybe not cured but definitely at least severely slowed down because if you can make all your cells in your body young again theoretically you could live forever and that's the immortal jellyfish is uh at least for it lives for 5 000 years or something ridiculous because it can de-differentiate its cells it can make its old cells young again at will, which is kind of crazy.
Starting point is 00:30:25 Yeah. I mean, so you mentioned Yamanaka and I know he was known as discovering these, as you described, induced pluripotent stem cells. Yeah. I think induced meaning he sort of like, you know, like figured out a way to create them pluripotent meaning these are some, I guess, then they often start with like skin cells, just really basic cells. And then- Yeah, skin, exactly. Right, and then find a way to literally turn them into stem cells that could then turn into
Starting point is 00:30:51 whatever type of other cell that you want it to. But that research, if I remember correctly, it's probably about, it's gotta be about 15 years old at this point. When I'm not- It's almost 20, it was 2006. Yeah. Right, so my question is,
Starting point is 00:31:04 because you're not seeing a lot of those ipscs in clinical or out there and like so what's we are now because the problem was up until now the risk with these ipscs is because when you coax them you're coaxing a cell basically to become young again but that has some risk it. And the biggest risk with it is that they're essentially embryonic in nature, so they can grow into tumors or cancer. And sometimes the DNA can be damaged. And sometimes maybe it might turn into something you don't want to turn into if you put in the body. So learning how to differentiate these cells into the right cell lineages and making sure the local environment you put them into do what you want, that took some time to figure out. But for the most part, it has been figured out.
Starting point is 00:31:48 Meaning they have figured out how to differentiate these cells into neural progenitor cells, into beta islet cells for the pancreas, into cardiomyocytes for the heart. So now we have all these different processes to differentiate these cells. And there's a company that we're working with specifically that has a technology. It's their proprietary tech that prevents these IPSCs from growing tumors or cancer. It's called FailSafe, and it's basically a gene edit inside of the IPSCs. So if they start replicating uncontrollably, if you have uncontrolled proliferation, it will act as a kill switch. So meaning it'll stop the cell from dividing. So you have that safety mechanism built into it. And
Starting point is 00:32:29 that's the company we're using. And that's the reason we partner with them is because of that technology. So we can feel comfortable putting these IPSCs into patients because we know they have that fail safe built into it. Yeah. How far are we now with actually seeing patient outcomes with these IPSCs? Well, Blue Rock Therapeutic is the one that did a clinical trial for Parkinson's and they took IPSCs, but these don't have the fail-safe mechanism. So there's obviously some risk of having cancer potentially, but it's probably 1% or so, but obviously patients were okay to do it. And so there was 12 patients or so, and they took these iPSCs and they turned them into dopamine producing neurons. And then they
Starting point is 00:33:10 transplanted them via surgery into the area of the brain where they lose the dopamine producing neurons called the basal ganglia. And they actually engrafted, meaning patients were actually producing new neurons that were able to produce dopamine. So this is the holy grail, right? You're actually creating new tissue that's fixing the problem instead of just masking it. And these patients go into remission, which is unbelievable. And the dose, there's two dosing groups and the dosing group that had higher seem to have better results. So it's just amazing to see the potential though, of what this technology can do. And I think this is just the beginning of the era of the IPSC era. There's 40 IPSC companies now, I think, and they're just
Starting point is 00:33:49 exploding. And it's definitely gonna be, you know, there's not gonna be 40 companies in 20 years from now. There'll probably just be a few that end up having the technology and owning it and really getting the best results. But this is the field regenerative medicine is headed towards now. Yeah. I mean, that's amazing. Especially when you talk about the results in the brain like that, because I was always taught that, you know, you hit a certain point in life, like you have X number of brain cells and yes, there's neuroplasticity, but that's largely about, you know, synapses rewiring. It's not, you're not generating new neurons, you're not generating new brain cells, but it sounds like what you're describing is actually like generating new neurons. Exactly. That's why I'm very excited about the neuro progenitor cells that we're going
Starting point is 00:34:28 to create. We're going to create them from IPSCs and we're going to explore that for dementia, Alzheimer's. And I mean, even MS there's so many different conditions you can use this stuff for. So I guess my curiosity around that is like, if we take MS or Parkinson's as an example, if there's some sort of genetic signal,
Starting point is 00:34:45 or maybe I'm making an assumption here, if something's happening, which is basically stopping in Parkinson's case, you know, like dopamine generating neurons from actually like generating dopamine anymore. And then you do an IPSC intervention and all of a sudden you start generating neurons that are generating dopamine
Starting point is 00:35:02 and that switches the counter to Parkinson's. Are you changing the genetics of the existing neurons or are they just dying and getting replaced by ones that actually are fixed? What's actually happening there? Yeah, no, they're actually, so the old neurons are dying off essentially because they're dead. You know, they're not doing what they're supposed to, or they're dysfunctional or they're senescent, meaning they become these zombie cells and they're not doing what they're supposed to, or they're dysfunctional, or they're senescent, meaning they become these zombie cells, and they're not doing what they're supposed to. So they're essentially just, you know, and they're not being cleared up the way they should. So when you put in these new cells, it changes the signaling and the local environment as well, which means it helps to reduce neuroinflammation, it helps with oxidative stress, and it helps with
Starting point is 00:35:41 other kind of cellular hallmarks, as we talked about earlier, that are associated with Parkinson's. Because we know that a lot of these chronic diseases, you know, have all these different hallmarks. So for example, in Parkinson's, they found that there was a trial last year that showed that even certain gut bacteria is linked to Parkinson's. So like gut dysbiosis, or having the wrong bacteria can increase the risk of Parkinson's, even Alzheimer's. So there's all these other things that are contributing factors, which I think ultimately are the ones that alter gene expression. So even if you have a genetic predisposition, I don't think genetics play that big of a
Starting point is 00:36:16 role as compared to obviously epigenetics, which we understand way more about now and how gene expression is altered and turned on and turned off based off the environment. Now that makes a lot of sense. So we're really kind of talking about this one cutting edge type of stem cell, the interpluripotent stem cells. And that's where the edge is. That's where people like you are just starting to actually do the work and the science behind it and using it clinically. But when the vast majority of people talk about having some sort of stem cell procedure these days, they're not talking about that. They're often talking about, you described earlier, mesenchymal or fat-derived stem cells. What are those and what are the common
Starting point is 00:36:59 use cases for those? Where does that make sense? Yeah. So mesenchymal stromal cells is a technical right nomenclature, but we just call them stem cells because everyone now says that. But stromal because they have a little bit of scaffolding effect and mesenchymal is just kind of an embryological term. But essentially, these are multipotent cells. They're not pluripotent. So that's important to remember. So what's the difference there?
Starting point is 00:37:22 Yeah, exactly. So pluripotent means they can differentiate into all three cell lineages called ectoderm, endoderm, and mesoderm. But multipotent just means they have what's called a trilineage differentiation capacity, which means they can only turn into cartilage, fat, muscle, and bone, really. So it can't go into all the different, can't grow new neurons or other things like that. So it can't go into all the different, it can't grow new neurons or other things like that. So there's much more limitations with multipotent mesenchymal stem cells as compared to induced pluripotent stem cells. So the question is, can we engineer mesenchymal stem cells so they have more pluripotency? And that's kind of where the
Starting point is 00:38:03 research is going now. If you just go to your typical doctor, I guess this is where there's problems in this field, is if you go in the US, they're going to tell you you're getting a stem cell procedure, but stem cell procedures are still illegal in the US and not FDA approved. Obviously, that's not stopping people from doing it, which I get. I mean, I understand people don't agree with them, but at the same time, there, you know, there's a big black market now for stem cells and exosomes and all this stuff. And it's creating some problems because it ruins the reputation of people who are trying to follow the rules and trying to do the good work. And if you go to a doctor in Florida where they're doing stem cells, they're more than likely
Starting point is 00:38:40 either offering you your own stem cells, which aren't true stem cells. So you're taking your bone marrow or your fat, and then they're just processing it, and they're injecting it back in. Those are technically committed progenitor cells, which means they've already committed to a cell lineage, and they can't actually turn into different types of tissue. They're just more reducing inflammation. They're more signaling molecules than anything else. And then let's just say if they're in Florida, Florida is the most common place. That's why I'm using Florida as an example, where there's so many clinics that are offering this.
Starting point is 00:39:07 And say you get IV stem cells or exosomes or something like that, and they get from umbilical cord, they're usually going to be derived from umbilical cord tissue, but they're not often going to be culture expanded because culture and expansion is very illegal in the US. And so FDA can get you can get quite a bit of trouble for that. If you're not doing it under a clinical trial, it's typically that's what most people are getting, I would say, for the most part are getting umbilical cord tissue, or exosomes, which are kind of the soup that the stem cells grow in. Personally, where I do most of my work is in
Starting point is 00:39:39 Los Cabos, Mexico and Dubai and Europe and Tokyo, I'm working in the summer. These are all places where stem cells are regulated and approved. And, you know, we can debate all day about why they're not approved. But the point is, they're just not approved yet by FDA, probably more so to do politics and safety or efficacy. But the problem, as we were saying, with these mesenchymal stem cells is that they're multipotent. So meaning they don't really have that much pluripotencies. A lot of patients are thinking they're getting these in hopes they're going to regenerate new tissue, but they're not really doing that.
Starting point is 00:40:08 They're just kind of reducing inflammation, which can still be very helpful for chronic pain, longevity too, because inflammation and chronic inflammation is a big driver of aging. So they're still useful, but just being very clear and transparent about what they can do and what they can't do. And to that extent,
Starting point is 00:40:23 we are now working with a company that has something called MuCells. MuCells are very fascinating. And this is getting a little bit into the weeds, but I think people will find this interesting because it's another Japanese technology. It's called multi-lineage differentiating stress enduring cells. So MUSE, M-U-S-E. And M-U-S-E, MUSE cells are usually only one to 5% of the population of mesenchymal stem cells, but they're responsible for most of the pluripotency. MUSE cells are pluripotent basically, and they're stress enduring, meaning they can survive harsh environments, whereas regular stem cells, a lot of them die once you inject them into the body. And so mu cells, if one of the goals of the last kind of decade of research has been, how do we increase the mu cell concentration, because then we can increase the efficacy of
Starting point is 00:41:15 mesenchymal stem cells. So there's a group that use of Japanese technology, and instead of being one to 5% of mesenchymal stem cells, they're like 70%. So you have potentially like a 30X increase in the mu cells. It's gonna be significantly better in terms of effect. And I'm seeing this clinically now. I'm starting to use these mu cells. And the results have just been incredible
Starting point is 00:41:37 for chronic inflammation and a variety of conditions. Got it. I mean, what I'm hearing in part is like, if you live in the US, be careful. Yeah. Like really be super careful and ask a lot of questions and not necessarily that any people who are providing services like regenerative medicine services are malintended, but it sounds like just the learning curve here and the speed at which things are developing is so fast that it takes a huge amount of effort to sort of like stay on top of what's going on. I'd always been sort of like,
Starting point is 00:42:09 before I heard about the Yamanaka cells, the IPSCs, I heard about mesenchymal stem cells. And I think that's probably, if anyone's talked about it or thought about it, that's what comes up. And then the only options were, well, it's either bone marrow derived, meaning like you take a little bit of bone marrow and basically spin it out, or it's fat derived. You take a little bit of fat from your body and derive it from that. And those cells then have the ability to differentiate into damaged tissue and in doing so heal it. But it sounds like you're saying that's not really what happens. No.
Starting point is 00:42:43 Dr. Arnold Kaplan wrote a paper on this in 2017. I believe it was published in Nature. And it was basically, we need to rename these cells, call them medicinal signaling cells. Don't call them mesenchymal stem cells because they're not stem cells. They're signaling. They're essentially just doing signals that reduce inflammation. They're not really differentiating and turning into different types of tissue. And in fact, even if you were to, let's say, isolate the mesenchymal stem cell from the fat or bone marrow and then culture and expand them, the problem is after age
Starting point is 00:43:15 40, your stem cells, just like your body, age. And so they undergo exhaustion, which means they don't work that well. And so do you really want to use your own cells after a certain age? Probably not. And wouldn't you rather have babies or engineered cells that are embryonic in nature? So just intuitively, I think most people understand that their cells aren't going to be great as what's off the pro allogeneic cells, which are from donors. And people sometimes obviously are concerned about don't you have to match, but with mesenchymal stem cells, you don't, they have what's called low HLA antigen expression concerned about, don't you have to match? But with mesenchymal stem cells, you don't. They have what's called low HLA antigen expression. So they don't express much of the antigen.
Starting point is 00:43:50 So there's no risk of graft versus host disease. It's not like hematopoietic stem cells, which are bone marrow stem cell transplants that you have in the hospital. Those you have to have match, but not for MSCs. Got it. So if you do have that procedure, especially in the US, and you feel some relief, it's very likely not because the tissue has regenerated or been healed. It's because inflammation in that area has been reduced at least temporarily.
Starting point is 00:44:17 And that's probably what you're feeling. So interesting. And I guess, as you noted, the potential ethical issues, well, you know, I think there have been wide debates about the use of umbilical stem cells and like people feel one way or the other about it, but it sounds like the IPSCs are kind of like, they're the next generation workaround around this because you can just take anybody's skin cell and effectively turn it into something close enough to an umbilical one, right? Yeah, no, it's in fact, it's probably even better than umbilical, because it's more like embryonic. I think the ethical issues often were from embryonic stem
Starting point is 00:44:49 cells, because you have to take them from aborted fetuses or growing fetuses in labs. And obviously, there's so many ethical issues around that. Plus, they can cause cancer. And there's but there's that doesn't stop people from offering them. There's clinics in Mexico, I've seen them, they offer embryonic stem cells. It's scary, number one, and it's dangerous. And so you got to be very careful where you go. And that's why, unfortunately, I think the stem cell landscape outside of the US too is riddled with people who are just taking advantage of patients. And we're trying to really educate people and just trying to do things the right way while understanding that this is still a very new field and we have to do a lot more research to really push it forward.
Starting point is 00:45:27 Yeah. And we'll be right back after a word from our sponsors. Mayday, mayday. We've been compromised. The pilot's a hit man. I knew you were going to be fun. January 24th.
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Starting point is 00:46:17 vary so you mentioned the use of these um the the ids id induced pluripotent stem cells in things like neurodegenerative conditions. More broadly, what about things like heart disease, diabetes, or other sort of like chronic systemic illnesses? Yeah, well, it turns out that all disease starts in the cell. There was a good Nobel Prize laureate who said that, and I think that reigns true for any chronic illness. So where does cardiovascular disease start? It starts in the blood vessels called the endothelial cells, and the endothelial cells become dysfunctional. Why do they become dysfunctional?
Starting point is 00:47:03 Because there's all these toxins, there's poor lifestyle, there's all these things that lead to the cells in the lining of your blood vessels to start getting damaged, and they can't repair themselves. Like we talked about earlier, it's that city that can't repair the library the way it wants. And then eventually, and we think there's something called the unitary theory of aging. And it's called unitary theory because we think that the most foundational cause of cellular dysfunction and chronic disease progression has to do with the mitochondria. So mitochondria are much more than just powerhouses. As we were taught in high school biology, they do a lot more than that.
Starting point is 00:47:42 They help to maintain tissue homeostasis, which is very important because that's entropy over time and changes in the epigenetics is what really leads to aging. And so the mitochondria become dysfunctional and that signal, meaning they can't deal with oxidative, there's too much oxidative stress. They can't, the free radicals build up. And then that leads to inflammation, senescence, and all these other kind of hallmarks of aging. So for cardiovascular disease or diabetes, at a very fundamental level, they still have the same kind of dysfunctional cellular problems. And if you can restore those cellular dysfunctions, then you can help to treat those conditions. And that's why stem cells are
Starting point is 00:48:20 almost magical sometimes, because if they're done the right way with the right dosing and especially with these engineered stem cells now they can treat a variety of conditions and that's why it's confusing for traditional physicians and it almost looks like char and i thought it was charlatan thing too when i got into it's like how can they how can stem cells treat like 20 different conditions that doesn't make any sense and but then once you understand it you're like oh it's because it's treating the underlying cellular dysfunction and restoring the cellular signaling and the processes that are going wrong in the first place. So, for example, in diabetes, they've done clinical trials just with bone marrow stem cells or umbilical cord stem cells, not even engineered IPSC ones. And they culture expanded, though, and they inject them into the pancreas and patients can get off insulin.
Starting point is 00:49:00 And it's for type two diabetes. So how is it doing that mechanistically? It's not regrowing new pancreas cells. It's just because it's reducing inflammation, helping with oxidative stress, helping with the telomeres, helping with all these different things that are the hallmarks of aging. It's almost like you're talking about like the magic bullet. Well, that's it kind of, I think it's about figuring out what cell is going to be the magic bullet. But I think one day we will engineer a cell that will be a magic bullet. So here's where my brain is going.
Starting point is 00:49:31 Also, I'm so curious about this. If this can literally go into your body and help with so many different things from acute things to chronic things, let's say the typical person in their 40s, 50s, 60s or later, they're going to have a lot of different things that need remedying in their body, like all at the same time. How does the stem cell, like you put it into the body and the stem cells like, oh, I can fix that, I can fix that, I can fix that, but has it nowhere to go? Yeah, yeah, no, especially so the mu cells specifically, which are the subpopulation of mesenchymal stem cells, so they're inside of them, they seem to be responsible for most of the homing ability.
Starting point is 00:50:09 So there is a known homing ability of MSCs, of mesenchymal stem cells, but the mu cells are even much more so. So we think there's something called chemokines, which are released when tissue is damaged. Chemokines are signals that say to your body, help, come help me. And so your body mobilizes its immune response to do that. But then oftentimes that immune response leads to chronic inflammation. And that chronic inflammation is what kind of leads to so much degenerative processes because you get kind of stuck in this loop. And so what the stem cells can do is go in there and they change what's called the micro
Starting point is 00:50:44 environment and they change the cellular signaling. This is called macrophage polarization, which is just a fancy word for saying we're retraining your immune system. So instead of being a pathogenic phenotype where you're sending pro-inflammatory signals, you're now going to have a much nicer phenotype where you're sending anti-inflammatory signals. And so that's basically what's happening with these stem cells. When you put them intravenously throughout the body. So basically, as you described, like you could pick an organ and go directly into it. But if they're sort of like multi-system things you're talking about, it's almost like they have these built-in homing devices to figure out like, where's the most important place to go? Exactly. Yeah. Yeah. It is wild. I know. I read a paper a couple of weeks ago and they described,
Starting point is 00:51:29 they had a visual of how the stem cells go into the blood vessels and how do they home. It's almost like these cells are smart. And I think that's, and I think that's the conclusion I'm coming to personally based off also Michael Levine's work, who's a bioelectricity scientist. And he talks a lot about that with bioelectricity. But I agree with him in the sense that they're almost like these little, you know, smart little things that kind of know what to do when you put them in the right place. But it's just, it's all about the environment and the environment dictates the signaling that they're going to be told and how to know to do the right thing depends on the
Starting point is 00:52:02 environment. And that's why if the microenvironment has too much inflammation or is hypoxic and there's all the wrong signals being sent, then the stem cells won't work. So that's why prepping the body and having the right microenvironment is very important for the best results. Yeah, that makes sense. I mean, as you're describing that, I remember talking to a physician who was in the field at one point, and they were saying that they have been injecting stem cells IV and then using effectively shockwave therapy to induce inflammation in particular areas that they wanted to direct the stem cells to.
Starting point is 00:52:40 And the stem cells would kind of find their way to them because they'd intentionally inflamed that particular area. Does that make sense? Yeah, I've heard of that. I've heard of people doing shockwave or laser or other things to try to get the stem cells to go where they want to. But I think that's a crude way of doing it, personally. And I also don't know if there's any published data on that. I think you just have to engineer the cells so that they have better homing abilities, which is what we're doing now. Right. And it's almost like you're adding inflammation to a system that's already like inflamed as
Starting point is 00:53:10 a way to try and like direct these things. Yeah. And yeah, my counter argument to that also would be, we know that if there's too much inflammation, the cytokines, the proteins that cause that inflammation, they can interfere with the stem cells to do their job. Right. Yeah. So it kind of defeats the whole process.
Starting point is 00:53:29 The last thing I want to circle around, and I think this falls at least in part under the auspices of regenerative medicine is gene editing. I think a lot of people have read about CRISPR and sort of like the evolutions that are being made there is in your mind and in the work that you're doing, does that fall under? Yeah, because regener vagina medicine and the holy grail of vagina medicine is basically this intersection between cell therapy gene editing or gene therapy and tissue engineering okay so all three of those is kind of what's the next era of medicine and combining all three of those in a very sophisticated way is what's going to allow us to regrow organs and fix any disease known to man, I think. Especially once CRISPR becomes a reality, you should be able to fix any genetic defect.
Starting point is 00:54:10 And we're getting there. We're not there yet. But I think that's going to definitely happen as these technologies continue to evolve. Yeah. So in super simple terms, what does CRISPR, what does it do? It's basically at a very simple level. It's essentially just this bacteria. It's called the Cas9 system.
Starting point is 00:54:26 And basically what it does is you can take any cell out of your body and you could basically like imagine you take scissors and you cut out this coat of DNA that you don't want in there and then you can stitch it back together and then you can put it back in. And then you can change the genome in that way. But the problem is with CRISPR is that there's something called offsite targets. And this has been the biggest issue. And because people are probably wondering, why haven't we saved humanity? If CRISPR is a real deal, you know, because it sounds in theory, it sounds amazing. But there's all these offsite targets, which means it edits things
Starting point is 00:54:57 that we don't want it to edit. And there may be things, unintended side effects. And that's why it took 12 years for one product to come out. Finally, they finally have one. I think it's for sickle cell, if I'm not mistaken. Yeah, I was just reading about that recently, actually. Yeah, yeah. So I think that that's the first FDA or, you know, or was it European approved product. And so, but it took 12 years, and that's only one product, and it still has risks with it. And so I think we're still pretty far away from seeing this become a reality. I'm not saying CRISPR doesn't have a lot of potential. It has a huge potential, but it just seems like the commercial value of it is going to take a
Starting point is 00:55:32 lot longer than we thought. Now, the technology we're working with is called mini circles. And I may be biased because I work with them, but I think mini circles have a lot more commercial value. They don't have the same power capability as CRISPR because we can't cut out things and correct them, but we can add genes. So that's what our technology can do. So we can add any gene, any peptide or protein in the body up to 10,000 base pairs, which is fairly big, but not as big as obviously CRISPR can just pretty much do anything. But again, the good thing about our technology is that there's no offsite targets. So what is a mini circle? A mini circle is a plasmid that's derived from E. coli, a bacteria, and a plasmid is just something that is used to exchange information. So a plasmid is just,
Starting point is 00:56:20 when, if you look at under a microscope, it's just a circular strand of DNA. And so hence the name mini circle, because it's like a mini circle. And you can insert whatever gene of interest you want onto this mini circle. And then you can inject it into a patient and they'll tell the local cell there, hey, you have this new information. So your library now has a new book, and you can read that book. And they'll tell you to produce more of the peptide or protein that we inserted onto this mini circle. So you can add anything that we want on there. So you can imagine there's a lot of possibilities because we can add on any peptide and peptides are becoming very popular in the, in just general kind of public now because of Ozempic. But there's so many other peptides that we can do gene therapy forms of. So the first product we did was called folistatin gene therapy.
Starting point is 00:57:04 And the reason we chose folistatin is because it's a, it's been around for 20 plus years. can do gene therapy forms of. So the first product we did was called phallostatin gene therapy. And the reason we chose phallostatin is because it's A, it's been around for 20 plus years. It's very well studied and we understand all the mechanisms. And B, it helps to preserve muscle mass and increases muscle mass. And I think we all, like we said earlier, muscle is definitely the organ of longevity, as Dr. Gabrielle Lion always says. And we know that if we can help to slow down muscle loss or increase muscle gain, we're going to help with your longevity and health span. And so that's why we chose folistatin as our first target. And so we basically, it's that folistatin gene therapy. It's just an injection in your arm or stomach, and it's not changing your DNA, but all it's doing is adding this gene and it's telling your cell to
Starting point is 00:57:43 produce more folistatin. And then it goes into your blood and it does what it does, which is folistatin is a bioidentical peptide hormone that allows you to increase muscle mass and decrease the systemic inflammation. So it's quite powerful for aging. And we showed that in our clinical trial, which is being published momentarily. It's available on our website if you want to read it
Starting point is 00:58:01 at minicircle.io, but we are publishing it in the journal. We're just deciding which journal to put it in minicircle.io, but we are publishing it in the journal. We're just deciding which journal to put it in. Got it. And is that a permanent change? Is it short term? Do we know yet? It's the world's first reversible plasmid gene therapy.
Starting point is 00:58:20 So reversible, meaning you can take an antibiotic called tetracycline or doxycycline, anything in that class, and it'll act as a kill switch. Oh, wow. So that's why this is a real cool technology because it's reversible and there's no other reversible gene therapy in the world. And the other cool thing about our technology is that it's temporary. So because let's just say you don't want to do it again. I mean, everyone wants to do it again after it wears off. They last for 18 to 24 months. So it does wear off and then you can just get it done again. So effectively, if I'm
Starting point is 00:58:45 hearing it right, you're adding, let's say your body, like there's either you don't have the gene or the gene is damaged, that would let you produce an enzyme that's necessary for you. Exactly. Maybe down the road, CRISPR actually can swap in like the right one or fix a broken one. But what you're saying is this technology effectively says, well, we can take that, like whatever, like the SNP is, and we can essentially add it in, in addition to what's there. So even if the one that you have isn't functioning, you've now got like this extra one, that's actually gonna make it generate what you need. Yeah, exactly. And that's why it's a good technology for conditions
Starting point is 00:59:18 like cystic fibrosis, where they're not making enough of a protein, right? And that causes that. So we have all these rare conditions that I believe we can really change these people's lives. We're starting out with kind of longevity and cosmetics. We have copper peptide gene therapy coming out. But the reason we're doing that is because those are the ones that are going to generate revenue so we can reinvest into the more rare and more, I think, ones that are going to really change people's lives. Now, it's like my mind is exploding with the potential. I'm sure like you working on this every day, it's just got to be like, how do you even figure out what do I focus on?
Starting point is 00:59:53 Because there's so many different things you could choose, so many different directions you could go. Yeah. Between this and cellular engineering, my mind is very entertained. Yeah. And to a certain extent, it sounds like this, what you were just talking about, maybe it's not the long-term thing, but maybe this bridges a gap between now and when CRISPR hits a point where it's actually safe enough where you can actually make the genetic swap and then that lasts for life. Yeah, exactly. I could see CRISPR taking off
Starting point is 01:00:17 eventually and it'll just be unbelievable when it does. Yeah. Of either the things that we've talked about or things we haven't talked about yet. Is there like one thing that you're most excited about right now? Yeah, I think the thing I'm most excited about is definitely putting the Yamanaka factors into our gene therapy. So basically the Yamanaka factors are four transcription factors that we talked about that basically make the old cell young again. But we can take those. So we can take, they're called OSK and then C-MYC. But that last one is the one that's associated with tumors and cancer. But you can use OSK and you can still get cellular reprogramming. And so not maybe as strong, but you can still make an old cell relatively young again.
Starting point is 01:01:09 So what we're going to do is we're going to put the OSK into a plasma gene therapy, and then we're going to do a trial where we can see if we can rejuvenate organs and make them young again. Kind of the Holy Grail. Pretty exciting. Yeah, that is a reason to get up in the morning to sort of like dive into all of that stuff. Yeah. And the one we're going to do first, the organ I want to do first is the thymus because the thymus gland is this little gland that sits around your sternum and it involutes, which means it starts atrophying since you're basically a kid. And so it just becomes smaller and smaller as you get older and it becomes pretty useless by the time you're in your 60s or 70s, which means that's why so many people get chronic diseases as they get older because the thymus gland is so important for regulating your immune system.
Starting point is 01:01:51 So if we can do thymus regeneration, then we're talking. Yeah, that's amazing. It's so exciting. I feel like it's a cool time to be live when it comes to all of this stuff. It feels like a good place for us to come full circle in our conversation as well. So in this container of a good life project, if I offer up the phrase to live a good life, what comes up? Peace.
Starting point is 01:02:12 Being at peace with where you're at in life and being content with what you have and with who you have it with. Thank you. Yeah. Thanks for having me. Hey, before you leave, if you love this episode, say that you'll also love the conversation we had with Dr. Frank Lipman about the six pillars of well-being.
Starting point is 01:02:30 You'll find a link to Frank's episode in the show notes. This episode of Good Life Project was produced by executive producers, Lindsay Fox and me, Jonathan Fields. Editing help by Alejandro Ramirez, Christopher Carter, crafted our theme music and special thanks to Shelley Adele for her research on this episode. And of course, if you haven't already done so, please go ahead and follow Good Life Project in your favorite listening app. And if you found this conversation interesting or inspiring or valuable, and chances are
Starting point is 01:03:00 you did since you're still listening here, would you do me a personal favor, a seven second favor and share it maybe on social or by text or by email, even just with one person, just copy the link from the app you're using and tell those, you know, those you love, those you want to help navigate this thing called life a little better. So we can all do it better together with more ease and more joy. Tell them to listen, then even invite them to talk about what you've both discovered. Because when podcasts become conversations and conversations become action, that's how we all come alive together. Until next time, I'm Jonathan Fields, signing off for Good Life Project. Apple Watch Series 10 is here.
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