The Reversal of Age-Related Ophthalmic Disorders with Bruce Ksander, PhD
Our newest host, Rob Rothman, MD, is shaking things up to bring fresh voices and ideas to the OIS Podcast. In what turned out to be the most fascinating podcast discussion to date, Dr. Rothman had the privilege to speak with Bruce Ksander, PhD, associate professor of ophthalmology at Harvard Medical School, who has also contributed to the New York Times bestseller Lifespan: Why We Age and Why We Don’t Have To by Harvard colleague David A. Sinclair, PhD, with Matthew D. LaPlante.
Dr. Ksander opened our eyes, dropped our jaws, and completely blew our minds with the research he’s conducting on reprogramming damaged cells to reverse the aging process. Tune in now for this mind-expanding and thought-provoking discussion around the future of regenerative medicine and its potential impact on age-related eye disorders.
You don’t want to miss this conversation. Click play to listen!
Transcript:
Rob Rothman: Good morning. OIS podcast listeners. Happy to be speaking with you again today just by way of introduction. My name is Rob Rothman. I am a practicing ophthalmologist. I’m a glaucoma specialist by training. I am part of a large private equity backed group in New York, called OCLI. And I am also the Co-Founder and Managing Member of InFocus Capital Partners, which is a life science venture capital fund focused specifically on ophthalmic investments, we have 12 assets in our portfolio, and are nearing the end of our investment cycle. And it’s been it’s been a great experience. So far, I have been given the opportunity to conduct some podcasts for OIS. And having been given some latitude with regard to who I get to speak to I have been privileged with sort of roping in Bruce Ksander for my my my current podcast, who is an Associate Professor at Mass Eye and Ear at Harvard Medical School in Boston, who is involved with research, which I believe will likely put all of us out of business one day. And because of that, I think it’s important for us to know our enemy, and get some insight into what he is doing, which may be the reversal of disease at some point. So I think this should be an interesting and informative session, we’re going to get some insight on what Bruce is doing, why I so desperately wanted to speak to him. And we will go from there, Bruce, not to put any pressure on you, as you know, potentially the guy who’s going to put most doctors out of business one day. But why don’t you say hello to everybody give us a little introduction on your background. And then sort of let everybody know what it is you’re doing?
Bruce Ksander: Sure. First of all, thanks for inviting me and giving me the opportunity to talk about what we’ve been doing. So I’ve been a researcher in ophthalmology for my whole career, I did my graduate work at University of Illinois. And then I went down to basket polymer for fellowship. And then in the early 90s, moved up to Macedonia, and I’ve been at Harvard since then. And while I’ve trained in immunology, in the last 10 years, I’ve moved into stem cell research and more recently into the study of aging. And we’ve come up with some really exciting new discoveries just recently. Before we begin, I want to also acknowledge David Sinclair, who is Co-PI on this project. And actually this project, the idea behind it was started by him, he is a researcher in the department of genetics at Harvard, he has spent his whole career studying the mechanisms of aging, and is a very, very well known researcher in this field.
Rob Rothman: Right. So you know, for full disclosure, part of the reason that I became so interested in this is not only from the blurbs of press releases that have come out about the work that you’re doing, but also because reading Lifespan was game changing for me, and it’s a great book, and if anybody’s out there interested in learning about what’s going on in the field of age, and I think it’s probably one of the easiest reads regarding, you know, understanding aging, and what it is and why it is so important to tackle the concept of aging, not because you want people to live forever, but because the management of almost every disease in the body involves somehow figuring out how to affect the aging process. So it was a great book, and, you know, congrats to David for writing it. But I know that the work that the both of you are doing is integral to his being able to produce that that piece of literature. And I think that you’ll be able to give us some amazing insights into the science. I think that for the purposes of making this conversation. Understandable. What does it mean to age I mean, I’m in a place in the world right now where aging is very obvious and apparent. And you know, we all think I tell my knees and my back they’re pretty much a well aware of what aging is right now. But what is it? What is it from the study of genetics or from the science perspective, what is aging mean?
Bruce Ksander: So I think that the simplest step definition of aging is it’s the physical decline or physical decline of function of cells as you age. And so people studying aging, as a process, believe that this is due to an accumulation of injuries or damage that cells occur over time, and the accumulation of all these injuries, results in a loss or a change in function of the cells. So obviously, as you age, this can affect a variety of different pathways, but the end result is your, your cells, tissues and organs don’t function the same as time goes by.
Rob Rothman: So I think that’s so the question I have is, you know, when you talk about age and the broad term of age, there’s different types of age, right? There’s chronological age, you know, how many years? Or how many trips around the Sun have we taken, and then there’s genetic age, right? Because I have, you know, 90 year old patients who are playing golf and driving themselves to the office than going to the gym, and then heading out to dinner that night, and I’ve got 90 year old to get wheeled in, and you can’t, you know, function at all right? And there’s, they’re the same chronological age, they’ve taken the same number of trips, you know, around our star, but they don’t necessarily have the same age. Right. So what is, what does that mean? Like? How do we determine how old you really are?
Bruce Ksander: So actually, that’s an important background piece of information for our research on reversing aging in the retina. And so this part of the story started about 10 years ago with an investigator Steve Horvath at Stanford. And he was the first to develop a biomarker or biological marker of aging. And so what he did was, he is a geneticist, but an expert in bioinformatics. And he took the known genetic sequences that were available in a variety of different in humans and rodents and all different types of mammals. He looked at that. And so what was known what is that as you age cells accumulate markers, called epigenetic markers. And I’ll explain what epigenetic markers are in just a minute. But it’s known that these markers accumulate, when you start out, you have none. And when you get to be 90, your genome is littered with these read these epigenetic signals. He took all that information. And what he did was he used different types of analysis. And he identified specific epigenetic markers that could predict chronological age very accurately. So in other words, he could take your cells and my cells and without knowing anything about us, look at these specific markers. And within three to five years, tell us what our chronological age is. And so that’s the first time people have been able to actually use a biology marker to identify aging. Now what they’ve done since that is, so obviously, that first marker was validated with chronological age, but now they’re moving towards determining, like you said biological age. So a 50 year old may be very healthy or a 50 year old, maybe in poor health. They’ve now shown that they can distinguish between those by looking more closely at the epigenetic markers. So they do have a way now of estimating your health by your biological age through these epigenetic markers. And so this is it’s really a very, in itself an amazing field. Steve Horvath has made all different types of clocks. He’s now looking into specific types of aging clocks in different for brain. Hopefully, we will convince him to do the retina soon. And the more you focus on the aging of specific tissues, the more information you get. And Steve Horvath believes actually these epigenetic signals are a sort of a ticker tape readout of what is happening to yourselves, as you age.
Rob Rothman: So I’ve kept you know, I’ve complained that I feel sometimes like a 52 year old in a 72 year olds body. So in theory, in theory, you could take my genetic material, and you could run it through one of these clocks. Let’s just say, and you could guesstimate what might gin you could sort of say, well, yeah, you’re chronologically you’re 52 years old. But genetically, you’re six more like a 62 year old or 42 year old or whatever it is, you can determine based on these epigenetic markers.
Bruce Ksander: Correct. And then now they’re getting into more specific tissue specific clocks that can predict your time until malignant transformation. He has a recent clock that he calls the Grim Reaper clock, which you can guess what that clock is for. So it is an amazing new emerging field, just in looking at these epigenetic signals, and what does it mean for your health and your age?
Rob Rothman: So one day 23andme, and ancestry.com. And all these things will take your genetic material, say, Here’s where you’re from, these are your cousins. Oh, and by the way, you have six years to live. Theoretically, it could do that. Is that correct?
Bruce Ksander: Correct. Yes.
Rob Rothman: Okay. So that’s incredibly scary, guys, I understand, you know, how this gets done. So I don’t think that the audience wants to get into the nitty gritty of the science of how this figure of how this was figured out. But I do want to discuss just for a few minutes, you know, how this translates, at least, for the first part of the conversation, because I think this really needs going to focus on how this affects ophthalmology. But one of the articles that you were kind enough to send me so that I can become a little bit more knowledgeable about the aging process was how it is possible to convert any cell into a pluripotent stem cell. And that that’s been done repeatedly in the lab through what appears to be at least in reading it are fairly well established and straightforward process. And that it’s really a relatively well known sequence of events that has to occur, where you can take any cell and revert it back to its embryonic state. Is that correct? That I read that right?
Bruce Ksander: Correct. No, that’s, that’s so so actually, the, that’s a second critical piece of the story of reversing aging. And that is the identification of the factors that allow you to make pluripotent stem cells. So if you remember, back in many years ago, there was a controversy about embryonic stem cells, you don’t really hear that anymore. And the reason for that is nobody uses them anymore. And those were replaced with these induced pluripotent stem cells. So as you said, they can make a stem cell from they can take an epidermal fibroblasts and make it into a pluripotent stem cells. And actually, right now, the first clinical trials are being conducted, which use pluripotent stem cells that are differentiated into retinal pigment epithelial cells and transplanted into patients with geographic atrophy.
Rob Rothman: Okay, so we’re gonna get to that in a minute. Because that’s really that’s what made me feel like we needed to, you know, have this conversation is understanding that research. But let’s go back a step for just a moment. So, a little teaser there on pluripotent stem cells, but that’s obviously the the final common answer. But do we know why this occurs? Do we know why aging occurs in the first place? Do we have, is it a pre-programmed sort of godlike intervention saying people can’t live forever? And is there an implication that if we can reverse the aging process, that we’re going to keep people alive, you know, for eternity? And, and I think there are some, you know, minor ethical considerations that we should tackle here, at least from your perspective, not that I need to think that any of us have the answer to that, but has just been processed in conversations about how we control this type of science in a way that’s appropriate.
Bruce Ksander: So there’s, I think there are very important ethical considerations. Currently, the aging community is almost universally focused on something they call healthy aging. So the idea that we can live, you know, our current lifespan is into the 80s or 90s. But what people want is to be healthy through the end stages of their life. And I think what the aging researchers are directed at is obviously first curing the age related diseases that the chronic diseases that afflict people as they age. And I think that’s the ethics of that are very straightforward, but the techniques that we are using now and revealing also could be used later on to extend lifespan. And I think the ethics of that are very complicated, and I think are important to start to address at the early stage of this field now that we have shown that you can, at least in mice, reverse chronological age.
Rob Rothman: Okay, so that’s a big conversation, definitely not one for today. But I think that, you know, it was, as I continued my own personal reading, in the subject sort of felt that, that annoying discomfort that, you know, this could be really, really bad, you know, in terms of how we increase longevity and what the impact that can be on on population and how we navigate all the issues. And so they’re just blocked it out, because we want them to focus on disease and but to do that now, because
Bruce Ksander: Let me go back to the one question you proposed before that, which was, is aging inevitable? And, you know, and I think the answer to that is, people have, it’s intuitive that people think aging is one way that you, there’s no reverse to that. And the reason for that, I think is because aging affects all the different cells, tissues, organs in your body. And the idea that there’s a central mechanism controlling that is not very intuitive. And it was until I started working with David Sinclair was an intuitive to me at all. But actually, over the last 20 years, there is research in different areas, that points to the fact that the decline of tissues with age is not necessarily inevitable, and it can be slowed and even reversed. And I think this it’s a fascinating story, how this started. So it actually started with something I think people remember, I think, the first time an animal was cloned Dolly the sheep, I think that was widely reported in the news. And so the important point of that was what they did is called nuclear transfer to clone Dolly and they took an adult sheep removed the nucleus, and then they took a young egg, remove the nucleus from the young egg, put the nucleus from the adult into the egg. And that generated Dolly. Okay, so now at the time they did that, people said, well, because you used a nucleus, from an adult old male, that offspring was going to age abnormally. And it took them 16 years, but that’s the lifespan of most sheep. they’ve now studied, I think they’re a part of this in 2016. they’ve studied herds of cloned Dolly sheep, and studied it through all the different aging parameters and found that actually, those sheep age normal. So now what that means, though, is this nucleus that was in aging cell that had that change in function, due to the accumulation of the damage done over time, could be reversed and could still go back and support a complete lifespan of another organism. And then you could essentially reclaim that and put it back. So there’s, there’s no biological reason why there’s a age limit. At least. It’s not like the nucleus is exhausted and couldn’t be used after a certain time. So that’s the first part from that clinic for the second part was the mature aging nucleus was supporting a differentiated cell. And it had to be changed when it was put in the egg to now develop a new organism. Okay. And so researchers looked at that experiment, it said, So, something in that egg, something environmentally is changing that nucleus, and now reverting it backwards to that beginning organism stage. And they started to look at those factors. And it was that research that led Yamanaka to, he’s a researcher in Japan to discover what are called the Yamanaka factors now, which is a group of just four genes. And what he found was is if you take a mature cell and express these four genes, you can revert that nucleus back to a stem cell type.
Rob Rothman: So hold on, let me interrupt you. So you’re saying that you can take any cell from any human being expose or induce the expression of just four genes in that cell, no matter where it comes from. It comes from my skin, my brain, my heart, whatever one cell, expose the or reduce the expression of these four genes, and it becomes a pluripotent stem cell that can do anything and in the embryonic and in the embryonic state or in the embryo illogical state can actually create a new Rob Rothman.
Bruce Ksander: Well, so actually,
Rob Rothman: Nobody wants that, by the way, nobody wants that. So don’t, don’t ever let that happen.
Bruce Ksander: But so the the pluripotent stem cells are not totally potent. totipotent means you could make a new Rob Rothman but I can’t make the extra embryonic tissue the placenta and, so if you add that you could then clone somebody, but the pluripotent stem cells can make any tissue, tissue or cell. So people now have looked at the conditions where they culture the stem cells, and they differentiate into rods and cones, RPE cells, you know, muscle cells, it is the coolest thing when you culture in conditioned media to make cardiac muscles in a dish, you see the cells beating, it is the most amazing things.
Rob Rothman: So okay, so again, we could, I can probably spend 10 days talking to you, but let’s sort of focus it back to ophthalmology for a second. So in theory, we have an unlimited supply of pluripotent stem cells, right, because you can take any cell, induce these four genes, it’s shocking to me that it’s only four, but you can induce these four genes, turn it into a pluripotent stem cell and create the needed tissue. And I would assume that you have to also create a certain environmental meal you for those cells to grow in, in order to become RPE cells. Even if you take an RPE cell from somebody, and induce these four genes and expose it to an environment which causes it to become a myocardial cell, it will become a myocardial cell, right? So it has to be controlled in a way where so how do we get that stuff? Where does that go?
Bruce Ksander: People a lot of labs that studied the different differentiation steps. And they’ve essentially done that by looking at the transcription factors that they find in RPE cells, and then through this stepwise procedure, find these long differentiation signals in vitro to make an RPE cell and then they validated that those actually are in RPE cell. And so the first clinical app, so this created a really a revolution in regenerative medicine. And I think ophthalmologists should be enormously proud of the fact that the first application of induced pluripotent stem cells was in the treatment of patients with geographic atrophy. And so they’re transplanting in these differentiated cells from the patient. And in an attempt to restore vision. And so this led to the the first phase of reap what’s called, I think, is called reprogramming where you take out cells, reprogram them, make them into differentiated cells, and then surgically implant them back into the diseased tissue. Okay, and so that’s, you know, the clinical trials for that type of treatment are going
Rob Rothman: and that’s going on. So that’s going on right now. So where is this occurring?
Bruce Ksander: So the original clinical trials in Japan, there’s also one at University College London and in California. So those types of replacement techniques are going on in those major centers.
Rob Rothman: And just so I can clarify are these are the patients who are enrolled and again, whatever you feel comfortable discussing, please, you know, feel free to discuss but don’t disclose anything you’re obviously not allowed to, but I’m assuming that these patients are using their own pluripotent stem cells.
Bruce Ksander: And so the original trials were using their own, it’s autologous. And the reason for that was, obviously you don’t want an immune response, but they ran into problems because they, the reprogramming, they have to look extensively at any genetic changes. So obviously, they want to make sure that reprogramming doesn’t insert any type of abnormal mutations plus the differentiation protocol to make mature RPE cells, it ended up it took them a year just to generate enough tissue for one patient. And so that became untenable. So now they’re looking at Universal donors HLA matched pools of cells that would be available for transplantation.
Rob Rothman: Okay, right, I think it would probably be bad if you transplant to the cell in the RPE that turned into be, you know, myocardial cell growing in your retina, or you get some sort of teratoma like growth of these uncontrolled, sort of out of control growing cells. So the programming process is always critical. And there has to be some proof that these cells are going to perform the way they’re supposed to perform. But ultimately, there they are RPE cells being being regenerated into RPE cells.
Bruce Ksander: But so I actually think, though, that while this is very promising, and very new, it’s the first stage in regenerative medicine. And I think now, we’re moving on to a next stage of Regenerative Medicine, that’s not dependent on surgical manipulation, which is where we’re able to try to reprogram the cells within the eye in vivo.
Rob Rothman: Right. So you can take the cells that have become damaged and dysfunctional and reprogram into functional cells,.
Bruce Ksander: Right. And so that that was related. So when Yamanaka discovered these four genes that could make pluripotent stem cells, they discovered quickly something else. And that was, remember, I told you that as you age, these there’s an accumulation of epigenetic signals. So if you look at the epigenetic sequence of that aged donor Dolly nucleus, when they reprogrammed it, they found that the reprogramming wipes clear all the epigenetic signals from that nucleus. So it went from this aging epigenome to this clean start from scratch clear way the epigenome. So originally, they thought, Oh, this is bad, you know, it’s you’re losing all this information. But they found also then that know that these epigenetic signals and accumulated once again, as the clone sheep aged, so that connected then this reprogramming with this epigenetic clock, so remember, Steve Horvath found that this clock was an indication of the cell aging. And now when you reprogram it, you wipe clean that clock. So essentially, they the aging community looked at this data and said, Well, you know, this is great. This means that we have a way to wipe clean the epigenetic clock and start over but they, what they wanted was not to differentiate the cell into a stem cell, they wanted a mature cell to remain a mature cell and only affect the epigenetic signals. Okay, so they want they want to take a mature retinal ganglion cell wipe away or wipe away some of the aging epigenetic signals, but leave that cell a fully mature functioning retinal ganglion site. And so, they immediately tried to start to reprogram in vivo. And so they took the Yamanaka factors, and tried to use that in vivo. And what they quickly found out was that that wasn’t going to work because when they express the Yamanaka factors, they got some pluripotent stem cells but because it’s in an microenvironment of you know, tissue and organs, they got this teratoma formation. So clearly there was a problem with reprogramming in vivo. Okay, and so, so now we have the the first so the first two segments of this was the epigenetic clock, the ability to reprogram cells into pluripotent stem cells. And now and also then we showed that aging is plastic in Dolly sheep. Now, the final piece of the puzzle was put into place originally by a researcher in California, one Carlo Belmonte, who who looked at the tumor formation using the anok Yamanaka factors in vivo and said, Well, what we read maybe what we need to do is just briefly, reprogram cells and then turn it off. Okay, so he took the four Yamanaka factors and he expressed them in a mouse that he can control those four genes. And he turned it on and then quickly turned it off. And sure enough, he found that this way he could erase some of the epigenetic signals. And he also could restore function in a mouse model of aging called progeria. So it’s that accelerated is the main use of accelerated aging. He’s still though, had a lot of problems with controlling it and controlling the malignant transformation. And so with that information, David Sinclair, and a graduate student in his lab, Yan Chen Lu, looked at that and said, Okay, so how can we modify this to get the desired reprogramming in vivo. And so they predicted that if they left out one of those factors, which was a gene called c-myc, which is a known oncogene, and is also associated with accelerated aging, they removed that, and now tried transient expression of just three of these factors in vivo, that they could erase the epigenome signals of aging, but not the differentiate the cells. And so by good fortune, I happened to be collaborating with David Sinclair on a different project, but I was in the lab, when Yan Chen, the graduate student, first started working on this project, and I was lucky enough to convince him that to really test reversal of age, you should look at the eye because of glaucoma, age related macular degeneration. So these diseases have the highest risk factor is aging. Right. And so it’s a great sight to try to reverse aging.
Rob Rothman: So this obviously translates to any age related disease, but specifically for the eye, as you said, age related macular degeneration and glaucoma would be the, I guess, the prototypes, and probably, I would assume would be the first targets for being able to control this process. Both of those diseases occur over a very long period of time. But I would assume have very distinct genetic features that you’ve been able to identify that allow them to be mapped and targeted and tracked in terms of how well you can be programmed, is that correct?
Bruce Ksander: Correct. So actually a critical component for the translation of this was, so we did these series of experiments. At first we took aging mice, and so aging mice, just like humans, you know, have a decreased visual acuity with age. So we took really old mice, and we transduce, the just the retinal ganglion cells and reprogram them for four weeks, and then stop the gene expression and measure their visual function. And I have to say, we started with working with David, and he really wanted to do the old mice. And I really wanted to do mice that had glaucoma. And I thought, because I thought the aging mouse experiment was never going to work because we were just targeting retinal ganglion cells in you know, everybody knows that the cells throughout the retina, lose function as you age. And so I thought just targeting the retinal ganglion cells, wasn’t going to work for aging mice, and we could only target the retinal ganglion cells because that was the vector we were using to express the Yamanaka factors targeted those first. So but so we did both experiments. To my shock, the aging mice gain visual acuity, after this four week treatment with OSK and also the mice treated with glaucoma, also regained visual function. And so what’s important about both of these experiments is the reprogramming occurred after the damage had occurred. So in the aging mice, obviously, the retinal ganglion cells were losing function, and this restored their function. After they had aged in glaucoma, we induced elevated pressure induced a loss of visual function from the elevated pressure, then reprogram the cells and showed that their function was regained in vivo. And so this, you know, to me was really an amazing result. But what was even more amazing and I still can’t get over this is when we isolated the retinal ganglion cells, and then looked at the transcriptome. So we looked at what genes, Gene products were being made. And we compared young to old to old reprogrammed, the pattern was very clear. So the there most of the majority of the genes as you age went down and function, a smaller group went up in function. And so there was if you just look at all the gene expression patterns in an aging retinal ganglion cell, a majority of them go down. If you then look at the transcriptome for reprogrammed cells, the transcriptome was returned to a young phenotype. Okay, so I, to me, that’s amazing, because what it means is, these reprogramming factors are going through the genome, identifying epigenetic sites that have been changed with aging, going to those sites, reversing the epigenetic signal, so that the genes now function as if they were younger. So we showed then also that the epigenetic clock of the retinal ganglion cells was sent back added time, so the cells were made epigenetically, younger, the transcriptome now, with change to a younger phenotype, all of those combined. To me, it’s still now amazing. I think what what David Sinclair’s lab is working on now, among other things, is the mechanism of how that occurs. And so if you think of it, it’s really quite amazing that you have these types of these reprogramming genes are forming complex and moving along your enormous genome, and identifying very specifically age related changes in your genome and then reversing them. And so how that occurs. Obviously, it must have there must be a code and sequence among the epigenetic signals that allows that to occur, and how that occurs is going to be a very biologically important discovery. But it’s clear that from our experiments that it does occur. And I think that, to me, has very important implications for the clinical translation of this procedure to eye disease.
Rob Rothman: I am, if we weren’t recording this, you know, and there wasn’t a camera, I mean, my jaw would just be on the floor right now. Because it is just fascinating to hear, that this is able to occur, and that there is an understanding in the lab of how this occurs. And I, you know, I it’s just unbelievable that we’ve advanced as far along in the understanding of genetics. And I think that anybody who has is listening to this will be able to understand how the progression of the science can absolutely cure anything, we can find out where these genetic abnormalities are and just fix them at some point. it’s possible that we are heading in that direction.
Bruce Ksander: Right. So the biggest problem like take glaucoma is a good example. The paper was just published this last week from Mass Eye and Ear that identified 172 new risk factors for primary open angle glaucoma. And so the issue and treating these multifactorial diseases is the fact that there’s no there’s no set pattern you can focus on to treat them when people try to do when it’s reasonable as they look for places in in pathways that funnel have a common funnel. So they so you would say we’re going to target a ptosis of retinal ganglion cells and they say we’re going to look for targets at the end of that funnel. And that’s how you would address the fact that it’s multifactorial and different in every patient. So the genetics of like, retinitis pigmentosa is very simple. It’s a one gene, one mutation, causes the disease. And now, it’s been shown successfully that if in the first gene therapies that if you put in the correct gene, you can now make those cells function. Okay, so that’s a very simple genetic disease. glaucoma, though, is multifactorial, and there’s no clear set of genes that lead to glaucoma. However, you know, essentially all of our diseases have some basis in genetics. So the problem is, in these diseases, how do you go about treating this. And so this, what I just described, for age related diseases has an opportunity to reprogram cells without actually knowing what the gene targets are in different patients, okay, because these reprogramming factors are just looking for age related changes. And they’re going to be different in different people, but they still target those. So for example, how we age is clearly going to be different. So it’s well, for example, it’s well known inflammation gets, there’s a more pro inflammatory environment as you age. But that’s achieved through affecting all different components of the immune response, you know, macrophage, phagocytosis, innate immune, cytokines, T cell responses, all of those could be changed. And it’s hard to know where you would target that. But reprogramming then would go through, and I essentially identify within these tissues, what are the age related changes in that individual and return them back to normal?
Rob Rothman: Right.
Bruce Ksander: So that’s the the premise for this is that it has a it can address multifactorial diseases, where it’s unclear right now, how to successfully target.
Rob Rothman: Right, that’s the future, right? The future is figuring that out, figuring out what what’s common, how to treat the common findings, or how to personalize this to individuals. And that will be the future now. So we probably only have a couple of minutes left. And I just want to know if there’s any initial commercialization of this, there’s obviously a lot of technology here. So is anybody gone out and tried to commercialize any of this in a meaningful way? It’s ophthalmology.
Bruce Ksander: So So actually, the technology for this was licensed through Harvard, to a company called, Life Biosciences. And the company is actually named Iduna, which is part of that it’s a company looking at treating age related diseases. And their first indication that they’re going to go after is glaucoma. And so they, it’s a new company, and they’re actively working on that now.
Rob Rothman: So that company is called what, Iduna.
Bruce Ksander: Iduna, I D U N A, part of Life Biosciences.
Rob Rothman: So they’ve so that’s the probably, I mean, point of the earliest companies that I’ve heard that specifically licensing technology, specifically on the aging process. So fascinating. I knew, you know, you figured that would occur, obviously sooner rather than later. It’s good to know that, that that’s happened. And I think that there’s a lot of exciting research and a lot of exciting potential for the commercialization of this technology. And as it relates to specific diseases. And I would imagine that some aspects of the technology are translatable across disease states, but some is going to be specific for eye disease are going to be technologies specific for brain disease and specific for a cardiovascular disease. And I imagine that we’ll start to see these companies popping up all over the place focused on specific targets.
Bruce Ksander: Right, so there are a few other labs is working on in vivo reprogramming, they’re not studying the eye.So we were fortunate to have some of the best in vivo results. There’s a group in Stanford that reprogrammed cells in vitro and shown a similar reversal of age and reversal function in vivo but haven’t done it in vitro yet. And there’s another group in Spain that’s doing in vivo reprogramming again, not in the eye, but in pancreas and muscle cells and looking at they’re seeing a similar effect on reversal of aging.
Rob Rothman: Bruce I have to, I have to thank you for, you know, sort of enlightening me and scaring me at the same time. And I think that the work that you are doing in collaboration with David Sinclair is absolutely disruptive with regard to the future of medicine. And I am excited for what this technology can do. I’m fascinated that we’ve actually gotten to this point in medicine, where we can actually contemplate even the thought of doing this. And it’s really an amazing accomplishment that I think the world will be grateful for in the not so distant future. I also want to make it clear that there will be no future Rob Rothmans, we are not going to go through the process of cloning me at all, and my wife will absolutely lose it. So definitely, that’s not going to happen. But if you could figure out a way to fix my hook at golf, that would be probably the most useful thing that you guys can come up with. So maybe we’ll figure that out one day, too. Although I don’t think there’s any cure for that. But just in closing, you know, thank you again, I really appreciate this. I think that if for anybody out there who enjoyed this conversation, I think, and I think you’d agree, Bruce, that that Lifespan is really a great place to get some information and some understanding of this. I think it’s a great book.
Bruce Ksander: Just a very good review of David’s lifespan book, in the Wall Street Journal just this past Sunday. Right? So if anybody wants a preview of what’s in there, they could look at that review.
Rob Rothman: I think it’s a great place. I think for anybody who’s really interested in understanding aging, and how it’s treatable, and how it’ll impact disease in the future. It really breaks it down pretty nicely into where we’ve been, where we are and where we’re going. I think that’s the basic structure of the book. And I think it’s, it’s a really great place to get some further understanding. And hopefully, we’ll continue to see the development of industry around us. And I think that’s a real potential for one day for, for physicians to basically just be observers of patients rather than actual needing to treat many and and I think that you know, that that is something that we can foresee as being a real possibility somewhere down the road. So I think we’ll stop here. Again, we could go on for a very long time. But again, Bruce Ksander, thank you so much for your time today. I hope everybody enjoyed this as much as I did. You can to get a chance. And you’re interested read Lifespan. And hopefully we can have another follow up call as new developments come out, keep updating people on your work. And as this moves closer towards reality, I think it’ll be even greater conversations down the road. So thanks to the thanks to Bruce. Thank you OIS, for the opportunity to have this discussion. And looking forward to future conversations.
Bruce Ksander: Thank you.