Gene Editing Moves from Science Fiction to Medical Miracle

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Welcome And Why Gene Editing
Announcer 0:00

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts, hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren 0:11

Hello, I'm Dr. Michael Koren, the executive editor of MedEvidence! And I have with me today Dr. Michael Hafran. And Mike and I are going to talk about something that something you may not have heard about before, but you're going to hear a lot more about it in the near future. And

What Genes Are And Do
Dr. Michael Koren 0:28

that's the concept of gene editing. Mike, welcome to MedEvidence, and thank you for joining me in this really pretty earth-shattering discussion about what is next in medicine and how we can maybe for the first time cure some things that we can only manage in the past.

Dr. Michael Hafran 0:46

Absolutely. And cure things in quite a permanent fashion.

Dr. Michael Koren 0:51

Absolutely. So Mike Hafran and I are actually working together as investigators on a few projects that use gene editing. So, Mike, let's just start out by telling the audience what is gene editing? What does that mean, really? And how is that different than the gene therapy that we talked about maybe 20 years ago that quite hasn't worked out the way we expected?

Dr. Michael Hafran 1:14

Sure. No, that's a great question. And thanks for starting off right there at the heart of the matter. You know, the interesting thing about, so let's just go backwards a little bit. So we are our cells, our bodies, we are composed and created from a program, a script. And those are called genes. And you know, there are only a four proteins that are really involved in that. And from these four, and the way they're combined, they kind of they're this the script, the narrative that generates us into human beings. All of those good things, as well as some of those bad things that come along with being a human being. And gene editing is the ability now, and you know, this happened after we kind of decoded the human genome, the ability to associate a particular section or a gene with a particular disease state. So the biggest challenge was first understanding how this works, but then it's just even more incredible, Mike. I'm sure you you're still fascinated by this the way I am, which is that you can determine which section is responsible for what we call a phenotype, an expression of something, whether it's blue eyes versus, well, some of us have no hair. So something very superficial, such as that, but also something very serious. Unfortunately, you know, the propensity to develop heart disease. Of course, it's multifactorial, but there are certain genes that can have an impact on that. And yeah, no, I I I think that's I just wanted to lay that groundwork, first of all.

Dr. Michael Koren 3:06

So, you know, to your point, only 30 years ago did we really have the entire genetic map of human beings laid out for us. It's only been 30 years. And now not only do we understand so much more, we don't understand all the genes, by the way, but we understand a lot more than we used to. And we now understand the genes that kind of went wrong. And I like to tell my patients that it's important to pick good parents, but because you really can't do that, you you kind of got what you got. And then maybe technology can help change those genes a little bit for us. And the other thing that's fascinating, you and I were just talking about we had gene therapy in the past where I remember 20 years ago when we were first talking about this, we would take basically a viral vector that had a certain gene, infuse it into somebody's heart, hoping that would grow new heart cells and see what happens. And that turned out to not be a very sophisticated approach to the way we change the way organs work. But that's different

Gene Editing Versus Old Gene Therapy
Dr. Michael Koren 4:10

now. So maybe talk a little bit about the difference between gene editing and just gene therapies, we're injecting stuff, hoping that some miracle occurs.

Dr. Michael Hafran 4:19

You know, again, it is pretty fascinating that the progress that's been made over just a couple of decades. And you're absolutely right. As we understand proteins and such at a very molecular level, we now have the and uh you know, I I think it is really important to emphasize that sometimes we just don't know all of the we can't associate or correlate this particular protein or sequence with a disease process. But of the ones we do know, you know, we've done a lot of extensive uh scientists, the entire scientific community has done a lot of extensive work, and we have developed technologies that can actually go in and specifically seek out the sequence that is responsible for a bad disease, uh you know, like a bad expression of the genes and can actually go in, whether that's kind of like the ability to snip out that section of the genome, of the human genome, or if it's even the ability to go in and almost do a one base, you know, sometimes they call it the uh pencil and eraser sort of upright.

Dr. Michael Koren 5:37

Yeah. Yeah, that's fascinating. So again, old school, which was only 20 years ago, just injecting a bunch of genetic material and helping things happen. The new way of doing things is to find that one place in one gene that's screwing things up. And you break that gene, and then when you repair it, you repair it in a slightly different way from the original form, such that such that that gene is not doing the bad thing anymore. How fascinating is that?

Dr. Michael Hafran 6:10

Yeah, it absolutely is. You know, I think there are two fascinating, just mind-blowing considerations. A, that we know where the responsible gene is, and that, as you just said, we've become so sophisticated. It is no longer we're just throwing in a bunch of genetic material and hoping, like, okay, let's hope for the best. No, it we can really narrow it down to the exact spot. And a lot of times these are just very small sequences, you know, series, or even just one base, base pair that can be uh targeted specifically and then altered so that you completely change the genetic machinery and what it is producing subsequent to that change and the impact on the body. And that's truly what you know that is the I'm gonna say the miracle of what gene therapy is today.

Real World Wins Like Sickle Cell
Dr. Michael Hafran 7:10

And it's actually working, it's been in practice, and maybe I'm jumping ahead here, but you know, it's been successful and approved by the FDA for like sickle cell disease and isn't it Elevidys approved for Duchenne muscular dystrophy, too.

Dr. Michael Koren 7:28

Exactly. Yep. Those are two that are approved now. So just to get into that a little bit more, so for sickle cell, and I believe Vertex and CRISPR are the companies that worked on that, is you take cells from the blood, the bone marrow, that are expressing a sickle cell gene. You're treating that so that they are no longer expressing that gene, but this is done outside of the body, and then you're infusing the new blood cells back into the body after the bone marrow has been kind of changed. You know, uh I in fact, what the it's it's part of a bone marrow transplant process by which the the previous bone marrow that was doing the bad thing is removed, and the new cells come in and then are providing services to the bone marrow that actually are doing the right thing. So that's been yeah, go ahead.

Dr. Michael Hafran 8:21

Uh sorry to interrupt, but that is absolutely that is a complex orchestration. And to do that with it really, truly for individuals with sickle cell disease, a devastating disease. And to accomplish that, you know, both outside the body, basically rewriting the bone marrow. That's the the the level of sophistication and thought and everything that's gone into that truly is it's really nothing short of a miracle, in my opinion.

Dr. Michael Koren 8:54

Yeah,

Editing Liver Cells For Cholesterol
Dr. Michael Koren 8:55

absolutely. Now, so with those successes that you've mentioned, we're now in a situation where we're looking at other diseases and we're looking at situations where you can actually do the repair work in the body without having to necessarily take the cells outside of the body. So you and I are now working on projects that are looking at gene editing of cells in the liver and only the liver. So we're talking about gene editing, we're not talking about changing your germ cells, which are the cells that you pass on for your next of kin, but these are cells that are operating in the body that will be changed in you, but not your kids necessarily. So you can still actually transmit the bad genes, but take care of the ones in your own body, in your liver, that are causing the problem.

Dr. Michael Hafran 9:41

Yes, absolutely. And you you kind of uh are bringing to front some some uh areas of concern, and I don't want to quite go there yet. And these are areas of concern shared by potential patients and that sort of thing, but you know, they have been really explored thoroughly and continue to be explored by the by the medical and scientific community, and that is Well, let's let's jump into that.

Dr. Michael Koren 10:05

Yeah,

Why Editing DNA Is Not Alien
Dr. Michael Koren 10:06

let's jump into that. Yeah, so I I think it's fair to say, you know, this sounds scary. What are the areas of concern? So let's talk about that. So, first, the concept of changing or editing a gene, just as a general rule, sounds, oh my God, this is crazy. Like, why would you even consider that? And the simple answer is that our bodies do this all the time. So the example I like to give to my patients is that when you're out in the sun, UV radiation is changing your DNA. And your body has to repair that constantly. And more times than not, 99.999% of the time it gets it right. But if it gets it wrong, you get you get a skin cancer, right? But the point is that your body has a mechanism to repair damaged DNA. And so what we're doing in gene editing is putting a little tick mark in in DNA and then repairing it in a way to make that gene less pathological. So I don't know if you have another way of thinking about that, but that's certainly something that our bodies do on a day-to-day basis. So that becomes way less scary when you know that we're doing it that way.

Dr. Michael Hafran 11:14

Sorry, I'm gonna interrupt because you bring up a very poignant or salient point, and that is that you know, our bodies are doing this all the time. This is how you know our bodies are constantly fighting or preventing cancers. And, you know, uh not just from the UV light skin cancer, that is something that's a great example because that is very relatable to a lot of people, especially in Florida, for instance. But, you know, the uh other processes are are constantly occurring where the body is engaging in its in its own natural gene editing or gene repairing. Let's use the word gene repairing mechanisms. I suppose it's an interesting way to think of like what we're doing or with these current studies with cholesterol or high cholesterol and in the liver, that really the body doesn't have any natural mechanism to add those hepatocytes or liver cells. But now we have the ability to apply an external sort of uh mechanical fix or genetic fix to do the job that I'm sure your body would have wanted to do it.

Dr. Michael Koren 12:27

If if your body could do it, it would do it.

Dr. Michael Hafran 12:30

Exactly. Exactly. Because I'd so we we all are aware of the issues of high cholesterol and the impact of very high cholesterol on causing early cardiovascular disease and other things.

Dr. Michael Koren 12:46

So sort of continuing on the point of the things that are scary, I guess the other thing that's scary when you talk about gene editing is that this is a permanent change in the way your organs are expressing themselves. So what what are your comments about those concerns?

Dr. Michael Hafran 13:05

Yeah, and that is actually I I find individuals have two big concerns, and you're spot on with the first one, and that is that this is a permanent change. And in the case of gene editing around high cholesterol, especially a specific type around familiar hypocholesteremia, which is incredibly high in lipid levels, uh, because of this genetic error, it fixes that, it fixes that in the hepatocytes, and it is permanent, which in the case of those individuals is a great thing. Because who wants their liver, and very just to be very brief, again, just to kind of put around, maybe people don't fully understand what this sort of situation is with the high cholesterol, but there are think of the the liver cells kind of have like these little myths, catching myths, and they catch cholesterol like to get rid of it. It's like you know, the catcher in a baseball game just out to get rid of it. But this gene in particular there can be a gene error that that there is machinery that will be that exists in your liver and it eats up, it it gets the pictures out, so you're losing the the the mitts that are doing the work.

Dr. Michael Koren 14:39

Right. Right. And that's and we call those we call those mitts receptors. That's the medical word for them. Yeah. So it's a good lay term. I like I like that lay term, but these are receptors that get the bad stuff out of there.

Dr. Michael Hafran 14:53

Absolutely. And then there are genes that for some people that exist where they they're kind of almost like overproducing the um, I don't know how I would describe it, like the cleaning up, and it's not the cleaning up crew, but it's the crew that gets rid of those catchers, and they're getting rid of them too fast.

Dr. Michael Koren 15:14

Right, right.

Dr. Michael Hafran 15:15

Um, so you're losing those receptors, and then those individuals have very high cholesterol levels. Right.

Dr. Michael Koren 15:22

So but this gene genetic reason, yeah. They can't clear cholesterol out of circulation because they have too few receptors, for sure.

Dr. Michael Hafran 15:31

Exactly. So what this gene what you know, right now, the study I I'm involved in, and you as well, isn't it? It we're in editing that crew, that demolition crew, that's what I was looking for. The demolition crew that goes in there and gets rid of those catchers. So we can stop that demolition crew that from doing uh an overtly active demolition crew from doing what it's doing. And I I think that is fascinating. And it's a one-time deal, you know, versus-

Dr. Michael Koren 16:06

-that's a key point. So we talk about the concern about something being irreversible, but the benefit of being irreversible is it's one treatment. You only have to do it once. So that's exactly why we want to do these things, is so that one treatment and then you're fixed.

Dr. Michael Hafran 16:27

Right, versus oh, and I'm sorry to interrupt, but you know, uh, what's the other option for individuals with this super high cholesterol? And I'm sure a fair number of people know it's taking medicines, taking daily medicines. And probably the most obvious group or heterogeneous group is what's called the the statins. And I'm sure everyone has come across individuals or that you're taking them yourselves, not because you have super high hereditary predisposition to really high lipids and cholesterol levels, but maybe you're lower. But there are some people that it's so high, even taking statins every day at the highest dose is not enough.

Dr. Michael Koren 17:09

Right. And to your point, a lot of these people have to take multiple drugs, sometimes more than once a day, to get the results that they need, or they need to give injections that are given over the course of several times a month, for example. So with all these technologies that led up to gene editing, there is the need for multiplicity. There's a need for giving it over and over and over again. Whereas in gene therapy, yes, it is irreversible, but it's also sustained. So we believe that one treatment should last for the rest of somebody's life.

Dr. Michael Hafran 17:43

Absolutely. And that's what the studies have shown and in various animal models and that sort

Off Target Risk And Germline Fears
Dr. Michael Hafran 17:49

of thing. And now I want to shift gears because I think this is the other, the second kind of fear or area of concern that individuals have. And that is that I've found talking to individuals is any sort of off-targeting editing. So there's the the permanence, and then but but that can be interpreted as good, as positive as well, which is a one-time fix. And then you have the positive results for the duration of your life, for the duration of those cells. The other concern that people have had is off-target editing. So, what does that mean? That simply means that the material or or the the the process, the machinery that's sent in doesn't just in this particular case, it doesn't target the hepatocytes or the liver cells and that demolition crew that's destroying those catcher mitts, but it would go into a different organ, like maybe the pancreas, or it would affect and this is one thing that a lot of people have brought up. Like it would affect maybe my germ cells, such as the ova in women or uh sperm in males, and then this would be repeated and become very rogue. So I wanted to first address that first subcomponent, which is off-target energy. You know, that can always be a possibility, but the probability because of how far we've gone with being able to select out and attribute exactly where the gene is and what the change is, the the ability to kind of go rogue is very, very low to almost non-existent. I don't know, Mike, I I know you're very much academically inclined. Do you have any additional thoughts to add to that? I it's such a big concern that people have expressed. I'd be interested to hear your thoughts.

Dr. Michael Koren 20:02

Yeah, it's it's an important consideration. And what I'd like to tell the patients is really two important issues. Number one is that we are targeting genes that are expressed in certain organs and not in all organs. So, for example, for a lot of cholesterol metabolism issues, we're really targeting genes that are expressed primarily in the liver. And so when we give a product, it's gonna go mostly to the place where the gene is expressed just naturally. So if you don't express that gene in your bone, it's not gonna go there. If you don't express that gene in your brain, it's not gonna go there. These are genes that are expressed primarily in the liver. The other thing is that we have mechanisms to concentrate the product to where we want it to go. So, for example, for some of the technologies that we're using, we're using something called GalNAc, which is a way to focus the therapy just to a receptor on the liver, to bring up the analogies that you talked about previously in terms of receptors. So that's another mechanism that we use. And then probably the most important thing is with computer technology and other ways of assessing the specificity of that segment of the genome or the genes, we know that the guide to the place where we want to do the gene editing is so specific to that spot and no place else that we're not going to inadvertently affect other genes in other organs. And that's a huge part of this. This is very rigorously tested for years and years and years to make sure that the sequence that we're using to identify the place in the genes that needs to be corrected is in that place and nowhere else. So this is really an important part of the technology.

Dr. Michael Hafran 21:53

Absolutely. And again, thank you. That's uh I love that explanation, and it really helps kind of. You know, the more people understand, I think it helps alleviate or explain some of the, I don't want to say misconceptions, but maybe it explains away some of the the potential doubts or areas for confusion. The other thing I want to emphasize, and I would love to hear your thoughts on this too, because it does come up as soon as people hear the word genes or genetics, they instantly think about progeny, uh, you know, progeny, sorry. Right, yeah, and uh

Dr. Michael Koren 22:36

-your germ cells, that's right.

Dr. Michael Hafran 22:37

Yeah, right. Packing this along in whether it's sperm or egg to the next generation. And you know, I really try to um explain absolutely not. This is this is it's not the sort of machinery that can get incorporated into those reproductive organs.

Dr. Michael Koren 23:02

Right.

Dr. Michael Hafran 23:02

Um and as you said, it it doesn't even target those areas. It it's it's almost like it's do not pass. You know, you're you're not allowed in here.

Dr. Michael Koren 23:14

So do your point. Yeah, it's a great point. Is that number one, the therapies are manufactured to not go to places where we pass on our genes. So you're absolutely right about that. But the other thing is that the studies we're doing now probably won't allow people that are capable of passing along their genes. So we're probably looking for people who are going to be a little bit older and not necessarily sharing their genetic makeup with somebody else to pass along those genes. And that's just another safety feature of these relatively early stage experiments that we're doing. So that's an another another piece of re of patients being reassured.

Dr. Michael Hafran 23:53

So let's talk about it. Sorry, before you go on, I just want to say, you know, to piggyback on what you just said, with with the way that the technology and the protocols are written right now, there is an extreme emphasis on safety, patient safety, participant safety, even though there have been you know therapies that are FDA approved, but they have gone through many, many, you know, almost a decade of research in actual patients. So I just wanted to emphasize that because I think it's important for

How Low LDL Can Be Safe
Dr. Michael Hafran 24:32

the yeah,

Dr. Michael Koren 24:32

yeah. So that's a good segue to a little bit more of the details about the projects that we're working on. So you and I are working on projects that are looking for people who have had pretty serious complications of atherosclerotic cardiovascular disease and offering them the possibility of these therapies that should provide a durable, if not lifetime, treatment for their particular genetic problems. And they're in areas where we know that the genes aren't actually necessary, and that's a really important point, is that we're looking at the type of genes that not everybody has, meaning that human beings can live their lives completely normally without these genes functioning. So what we're trying to do is create a scenario where people that have overexpression of these genes turn into people that don't express the genes at all. And we know that they live just fine, except they're way, way, less, way, way less likely to develop cardiovascular disease.

Dr. Michael Hafran 25:35

You know, and that's and I don't know if this is poignant with maybe social media or some sorts of urban legends, but indeed, especially when we're talking about very high cholesterol levels with the ability to drop these uh levels down considerably, you know, that there are people just naturally they have genes or the makeup where they don't have very high cholesterol at all, and they're doing fine. They actually they live very long healthy lives. So sometimes, and this is a good point. Sometimes I I have talked to potential individuals where they're concerned about, well, wait, what if my LDL drops too low? Mike, I almost want to say, that's great. That's what we all want. That's what we're driving towards. So we're not inducing, or this therapy isn't inducing a change that's going to result in an unthought- of or a secondary or uh or collateral sort of damage.

Dr. Michael Koren 26:42

Yeah. So to that point, a very famous paper in the New England Journal of Medicine discussed this group of patients that had loss of function mutations for a protein called PCSK9. And those people would live their lives with an LGL cholesterol of 15 or 20, super low levels, and live perfectly normal lives, except they didn't get atherosclerosis compared to that.

Dr. Michael Hafran 27:04

They didn't get all the bad consequences.

Dr. Michael Koren 27:06

Right. Right. You know, so it's a it's a great example of not needing that gene. And we want to reproduce that scenario for patients that have had complications of having an overexpression of that gene.

Dr. Michael Hafran 27:18

And you know, I think that's part of you know, like the the overall scientific approach, because you you know, even with sickle cell, you you don't individuals you don't need that that sickling of the red blood cells. Now it could be argued that, yeah, sure, actually it's kind of protective against malaria. And uh, you know, I don't know the total history, but you know, we have a good we have good control over malaria, so unfortunately, you know, and many people live without the sickle gene, and we're you know, everyone's doing well. So same thing. We're we're not going after something. We don't, hey, we don't have perhaps, you know, I'm gonna say this we just don't have quite the full extent of knowledge of going after or editing all the genes, but we're very specific and we're targeting where we want to go and what we can fix.

Who Qualifies For These Trials
Dr. Michael Koren 28:20

So let's change gears just a little bit. So we're working on projects as we speak with therapies that are available in more than one community in the United States. So, what type of patients are we looking for? What type of patients would be the perfect patient for these types of gene editing studies for cholesterol and lipid issues?

Dr. Michael Hafran 28:40

Sure. So in general, you know, I'm gonna say we're looking for for the most part, anyone from their early 20s up to 70 years old. You have to the main thing is you have to have the correct sort of defining gene situation. You know, and that's again, right now, uh familial familial hypercholesteremia. And there are two there are a couple different types. There's heterozygous and then homozygous. Heterozygous is you have one copy. Remember, it it's always two, it's always in pairs, so you have one copy of the gene. Homozygous individuals have two copies of the gene. You know, it depends on the therapy, the the genetic therapy that's being offered. Those are some things you need to one needs to consider. And then you know, there are other considerations again because we want to, as you mentioned, minimize the risk in these individuals. Most of these protocols and studies require that you don't have any sort of cardiac event that would be like a heart attack or unstable angina within the past year. You you know, you you can't have significant blockages that haven't been treated. There there's also a very important thing to consider with the liver is that, and that is you really cannot have any sort of underlying liver disease or like uncontrolled diabetes. And then of course, as you mentioned, because we want to take every precaution, you know, we we don't these studies are not designed for individuals that are uh looking to actively um start a family anytime soon.

unknown 30:28

Right.

Dr. Michael Hafran 30:29

Um those are kind of like I wanted to keep it kind of broad based here. Do you have any other thoughts on some of those general?

Dr. Michael Koren 30:38

I would say that we're looking for people who have total cholesterol levels north of three or four hundred before treatment, and LDL cholesterol levels north of 200 or 250 even with treatment. And those people would probably get the most benefit from this. And as you point out, you want people who are clinically stable over the last several months but had some complication in the past, so that we know that in fact they had some damage related to this genetic problem. So, you know, we sometimes run into people that have high cholesterol, but for some crazy reason, they never get atherosclerosis. They have no coronary calcium, they live to 80 and 90 or 100 without any cardiac complications. We don't understand that, but those are not the people that would benefit from this trial. The people who would benefit from this trial are people who have developed complications in their 30s, 40s, and 50s.

Dr. Michael Hafran 31:33

You're absolutely right. And you know, that's a very good point. And I didn't mean to kind of say, like, oh, you know, anyone if you have don't have those things, you can come in. But you're right. We do want people where you know they're probably maxed out on medicines and they're still having complications. We just don't want anyone actively having complications. That's right. Because we want to create the safest environment for the individual uh as the process is occurring.

Screening Infusion And Early Monitoring
Dr. Michael Koren 32:07

Yeah, and to your point, we're going to do a very careful look at safety issues when patients present themselves to us before we give the green light from our standpoint as physicians to move ahead with the therapy. So talk to us a little bit about what happens. A patient says they have a history of familial hypercholesterolemia or FH. They call your office, you make an appointment, you find out that they're on statins, their LDL cholesterol is still 200. They've tried maybe a PCSK9 antibody, couldn't afford it, or had some issue in terms of access or tolerance. What does it look like from the standpoint of their experience in your office?

Dr. Michael Hafran 32:48

Absolutely. So I think your first point or your description was very good, in that the a large part of the process is that there's going to be a thorough, very thorough medical vetting, not only in discussion with me or any of the physicians at the sites or the sub-investigators, but because this is a gene editing study, typically I think the doctors are leading those conversations. And there's also going to be a very for some people, we do like to confirm if there is not a documented genetic test on their status, that might be part of the process. Another part of the process is a very thorough review of the actual individual's medical records. So of course, there's very long conversations, there's education. The individual is given a lot of time to think and ask questions. Once that process is done, then it actually picks up speed, in my opinion. That is, you know, what we will follow the protocol and in terms of the treatment therapy, but what one can expect is that there will be an infusion. That is how medication is delivered. It's very similar to uh the infusion therapies that are done today before to treat certain types of cancer, that sort of thing.

Dr. Michael Koren 34:18

Right.

Dr. Michael Hafran 34:20

Yeah, go ahead.

Dr. Michael Koren 34:21

Go ahead. Yeah, getting into what happens once people get accepted for the program and they'll they'll get that infusion. It'll be over several hours, probably, and then they'll be observed for one to four days very, very carefully to make sure that there's no untoward reactions. Uh some people may get a little bit of an infusion reaction, get a little bit of chills, but we can manage stuff like that fairly easily. Uh to date, we haven't seen any severe side effects to these uh type of infusions, but we're here to monitor that and to deal with whatever we see.

Dr. Michael Hafran 34:54

Right. And that's actually a great point that so far to date, we haven't seen anything that has really created, caused a stir, a bump up. Although there is evidence that there might be, because this is affecting the liver, there might be a little bit of a bump up over a week with what's called the liver enzymes. Again, nothing that has caused any sort of stoppages, that sort of thing.

Dr. Michael Koren 35:24

Almost to be expected that when you're treating the liver, that there may be a little change in the liver function test laboratories, but that is not of great concern for us at this point. So we're monitoring all these things.

Dr. Michael Hafran 35:35

And we're monitoring you carefully. Yeah, yeah. Exactly. And then you know, after after that period of observation, which usually is gonna be anywhere from two to four days, the the individual is discharged. But they are not just left alone, followed very closely by the staff, by the physician, and you know, there are certain tests that are done within the protocol, usually blood tests, and also the test to see what's happening or trending with uh with those cholesterol and LDL and lipid levels. So that process though, right, and this is something that individuals need to understand in addition to that permanence. This we'll we'll call it observation or surveillance.

Fifteen Year Follow Up And Costs
Dr. Michael Hafran 36:25

This is something that goes on for 15 years on average with these studies.

Dr. Michael Koren 36:30

So that's something that's an important point, right? Yeah, this important point uh for for patients that may consider this is number one, is that we have study grants that cover all the expenses for this, so there's no cost to the patients. Uh in fact, there's a budget for the patients for their time and travel. So patients actually get paid a little bit for participating in these things. And then there'll be up to 15 years of monitoring for free for patients as part of being a medical pioneer. So we recognize the fact that by allowing us to work with you on the early stages of research, in exchange, we're able to get you these resources that can be used over the course of 15 years that will hopefully be helpful to you in many, many different ways. So that is one of the benefits of being part of these programs.

Dr. Michael Hafran 37:17

Absolutely. And because these are really, you know, large companies, because I did have one participant ask me, oh, does that mean I need to be kind of like in my house for the next 15 years? Um, absolutely not. If you pay off your mortgage, fantastic, you know, yeah, go for it. But you know, there this is a very organized and structured system with a lot of points because everyone understands people move, but it's very important to you that you remain in the surveillance part of the program. And yes, these are very well funded, and there's a just a lot of a lot of extra eyes that are available to uh keep track of you through this journey, really. Because we want, just like you, you know, we want this to be a very you know, very, very positive and impactful uh sort of change for individuals. I absolutely you know what, Mike, this is what's so fascinating. Now we we're very close to having a permanent solution for some people, right?

Dr. Michael Koren 38:29

Right

Dr. Michael Hafran 38:29

Maybe for more people, you know, with high cholesterol. And you know, what is the number one cause of death in the United States? And I'm not sure if it is the world, but you know, cardiovascular disease, atherosclerotic cardiovascular disease.

Dr. Michael Koren 38:45

Absolutely, it still is around the world. In fact, in a lot of developing countries, it's become the number one. India is a great example of that, where as they've become wealthier, they've been subject to much more atherosclerosis, and it's it's actually the number one disease in India now, and it's actually more prevalent in India than in the U.S. at this point, which is a huge thing. Yeah.

Dr. Michael Hafran 39:06

Wow, I did not know that, thank you for teaching me.

Dr. Michael Koren 39:07

Yeah, I lectured in India not too long ago and I learned a lot about what they're suffering from. Anyhow, just final

Next Steps And How To Reach Us
Dr. Michael Koren 39:15

notes. Again, you're a patient, you have issues with your cholesterol, you've had some complications, maybe you've had some problems with other therapies. What what should you do next? Dr. Hafran, what do you think? Or how do you advise these folks?

Dr. Michael Hafran 39:31

And you're not making any progress. So for it for individuals that find themselves in those scenarios, whether they know what their you know uh genetic status is or not, the sponsors we we are able to do gene testing as well to confirm that. But I I was strongly suggest that an individual reaches out to either Dr. Koren, your site up in Jacksonville or Dr. Aggarwal's site in Orlando, or my site over in Boca Raton. And ask, there is absolutely nothing that's stopping us from you know speaking to you, kind of discovering more. But if you don't do something, you know, nothing isn't gonna get you anywhere. Uh and even if the matchup isn't quite right because of you know these protocols and the restrictions around those, I there are more and more of these studies. This is the future of medicine, and there are more of these studies coming along. So I strongly encourage anyone to reach out to any of those three sites.

Dr. Michael Koren 40:43

So the the next step for people would be to contact the number or the email address that'll be connected to this podcast. There will be different numbers and email addresses for different centers around the country and ask to come in and take a look at your situation or exchange some medical records to look at your situation, and then a medical expert will give you a very thoughtful analysis of whether or not gene editing is for you or something else might be in your best interest. And that's what we do as clinical research sites is we look at patients' records, we understand what their needs are, we understand what their previous problems were, and then we come up with some sort of solution, often through research, to address those issues.

Dr. Michael Hafran 41:27

Absolutely. Absolutely. I I I know that both you and myself and Dr. Aggarwal, while we were looking forward to engaging in conversations with people that are interested, you know, not just for themselves, but for the future generations and really the future of medicine, because this is the way medicine is going. I I would be shocked, Mike, if 10 years from now, 15, 10- 15 years from now, we're not treating a bunch of diseases in this fashion.

Dr. Michael Koren 42:03

Right. And the best doctors are the ones that can cure diseases

Closing Thoughts And Goodbye
Dr. Michael Koren 42:07

as early as possible. And I think we all want to move in that direction.

Dr. Michael Hafran 42:12

Absolutely. Absolutely.

Dr. Michael Koren 42:14

Mike, thank you for this great conversation. Thank you for being part of MedEvidence, and we look forward to working with you on these really exciting technologies.

Dr. Michael Hafran 42:22

Absolutely. It's always a pleasure speaking with you and such a great opportunity. Thank you.

Announcer 42:27

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