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Unlocking the Secrets of Cellular-Level Skin Health

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Unlocking the Secrets of Cellular-Level Skin Health

Ep. 59 - Alan Widgerow

41 minute view/listen

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Aug, 2022

Available everywhere you podcast

Plastic Surgeon. Professor. Scientist. The list of accolades is lengthy for Galderma's Chief Scientific Officer, Dr. Alan Widgerow - MBBCh(MD) MMed(MHS) FCS(Plast) FACS.

And with Galderma's acquisition of Alastin, he continues to lead Alastin Innovations in his new expanded role as CSO for Galderma. Using in-house R&D and organic research to launch moonshots into uncharted realms of subcutaneous tissue at a cellular level, Professor Widgerow takes a disruptive yet wholly scientific approach to optimizing skin health and rejuvenation in his role at Galderma. In this episode of The Technology of Beauty, he gets technical in his analysis of the pros and cons of synthetic exosomes, autophagy, the role of waste management in dermal health, and much, much more.

He also provides a look into a future featuring wearables that can tell you when you need to moisturize — and that's just a peek into what we have in store for you in this groundbreaking interview with Dr. Grant Stevens.


Full Transcript

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

Hello everyone and welcome back to the technology of Beauty, where I have the opportunity to interview the movers and shakers of the beauty business, and today is no exception. Today I get to interview Dr. Alan Woodrow, who is my buddy, my friend, full disclosure, and who introduced me to TriHex peptides. And he introduced me to Nectar and life as I know it with Alastin because I can tell you there's not been a day in my life since I met him and started using Nectar that I didn't have Alastin on my face.

And I know that sounds like hyperbole, but it's actually the fact. So finally, I was able to get Alan, Dr. Woodrow, to come up here from Orange County here to Manhattan Beach home of the technology of Beauty Studio. Thank you doctor.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

Absolute pleasure. And I agree. It's about time we had a little chat, so, good to be here.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

For years I've been asking you to come. So finally you're here. So first of all, thank you very much.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

Absolute pleasure. Good to be here grant.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

It's great to have you, buddy. I remember the day I met you, I remember at a little booth at a show and you showed me the science, the histology of the fibroblasts and the extracellular matrix and the effects of the TriHex peptide. And I remember my skeptical brain and my disbelief.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

And, and I think that's part of us as plastic surgeons. We are all natural skeptics. And I think that's probably what's influenced so much of the science that I've done in that we start off from an area of disbelief and then we've gotta validate it and prove it.

And that's been the mantra right through this whole process is and I remember that well as well. Sitting, in a booth Diane Goostree and myself, and Diane she's been on the program, the CEO of Alastin. And, we walked lonely walks in 2015 along some of those booths with a scientific narrative because the narrative at that time was very different to what was out there.

And and it was a lonely walk. And but it was exciting as well because we're introducing something new and different science. And although you were the skeptic, you were very accommodating in terms of listening to new science, which was great at the time. And I wanted to learn.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

So before we get to that though, I want to go back and let everybody know the listeners and the watchers and so forth.

So where are you from? You have a beautiful accent. I know the answer of this. Share with us where you're from, where you went to school, and then how is it you got here?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

So originally South African I get a lot of Australian or UK there's a sort of mix in the South African accent. So I practice as a plastic surgeon in South Africa for 20 years.

Went to the university there, which is pretty a well-known university in those areas called University of Witwatersrand. And qualified there to general surgery, first plastic surgery afterwards. and was involved in academics for a long time and then moved over to private practice being first started a lot of reconstructive and a mix of reconstructive and cosmetic, and then went over to cosmetic surgery for the last 10 years or so of the practice.

But was always involved in research. Always turned on by by research, and worked with some of the trade companies particularly in the wound healing space. It's been an area of great interest to me because wound healing is real the basis of all medicine. And so I became involved in companies like Smith & Nephew and helped them with some of the development of some of their products then.

And they really became quite entrenched in this whole wound healing space. Started a whole lot of clinics myself, but didn't, I wasn't doing the day-to-day stuff. I had wound healing experts doing that, but I was really interested in the science behind the products and the development of what we did there.

So that was a sort of pet side of mine on the side, sides of the practice. And as to have a practice and to do research, it's almost mutually exclusive. Exclusive, really difficult. So from there, from that perspective, I built myself up and I had the academic practice, and I was a professor at the university and I became a, the president of the society there, went through the na— the same sort of things that that you've achieved and accomplished, but on a smaller scale in South Africa.

But then at the same time, the background of the insecurity and the situation there in terms of my kids growing up and the insecurity of not knowing exactly what the future would hold, was driving at me all the time in terms of looking for alternatives. So having practiced and loved the specialty I'm, I managed to practice over 20 years, so it was an unfinished business.

And then I made the decision. I did have a green card on an exceptional academic merit basis, which is very fortunate. So the, the family could go over. But from that basis, I decided, look I've done my augments and my facelifts and my abdo plasties and all the rest of it.

Maybe it's time now to go back into the passion of research that always wanted to do, and that's really what I did. So we came over at the beginning of 2010 and I started off at the university of California Irvine. Worked with Greg Evans, a chairman there, started lecturing, becoming familiar with the program, and kept nagging him saying, get me involved in some researcher.

And eventually in 2012 that happened, he said, listen, I've got something better for you than just getting involved. Won't you take over our research division? And that's what I did. So I started, we changed the name to the Center for Tissue Engineering, and we have a very successful lab running there with PhDs and with post-grads and undergrads and medical students.

And. Biology students right across the spectrum. And I gotta say, the best way of learning, oh, the best way of learning is teaching. No question. And you're so familiar with that and with your programs, with fellows, you understand and appreciate the joy that goes into seeing these guys develop and how they, become personalities in their own from being the sort of raw material.

And then when they come out after a couple of years with you, that they become really, Good individuals and from a medical standpoint, I love seeing that these are guys that are not only in clinical medicine, but they have a research background. So they know the questions to ask and that's the most important thing.

So in, in a nutshell that's really it. It was amorphous from plastic surgery in South Africa to academics and to research and then to entrepreneurship okay.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

And you came over and you were at the University of California Irvine or UCI? Down in Orange County for those watching and listening working with Greg.

The chair and you'd been there a couple years. You started the se, you changed the name, the Tissue Engineering Center for Tissue Engineering, and then how did Alastin come into your life, or how did you come into Alastins life? How did that start? And then take us to the TriHex, if you can.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

That's a great question because what happened was after, so it was in 2015, roughly. I started in 20. Developed the and there was a lot of work that went into developing the lab and starting it over and getting guys, because don't forget a lot of the people working there on a volunteer basis, and they're working there for a year, two years.

Sometimes. I even had guys for five years and they would sub supplement their salaries elsewhere, but they just wanted research experience and for the cv, to look. Good. And to also actualize themselves in terms of research and areas that they hadn't done before. So developing that was important.

And by the time it came around to 2015 and I thought, okay, you know what? We're going nicely now. We've got a good platform for the lab. Let's see what is. Out there, it's time to actually start exploring what is out there in terms of startup companies and other areas like that. And I put the word out to my network that I developed over them a year or two.

Unfortunately you weren't there yet, grant otherwise. You would've been the first guy. I would've emailed, but I put the word out there and I said, listen guys, it's terrific at the university. I wanna continue here. I've got a good platform. But if anybody knows of any company starting up out there, I'm interested.

And it would be natural next step for me. That was on a Sunday evening by Monday at 12 o'clock. There were already a couple of responses to that, which is amazing and which is so beautiful about this country as well. And one of them was from a guy called Scott Glenn who said he had my details from John Garruto.

John Garruto, I didn't mention to you that I developed a scar product while I was in South Africa, and when I came out here between 2010 and 2012, what I did was I spent a lot of time working on deciding who I was going to license that technology out of the Scar product. Eventually I license it out to Skin Medica.

We're part of Allergan now, and my products are still there. The Scar Recovery gel. But during that process, I met a lot of good people. One of which was one of whom was John Garruto, who's an excellent, as formulator a super... And works with us at last, and he's my partner there and John had given my name over to Scott Glenn, who was the founder at the time, or supposed founder of a new company.

Nothing had started yet, and we met in a coffee shop in San Clement. Halfway. He was in, in Carlsbad and I was here in Orange County and we discussed over sort of coffee. He brought another PhD expert in biochemist and he said, look, he has this one, maybe two peptides he's interested in, but he'd really liked me to look at this and develop a white paper, give him sort of background of what it's all about.

And at the time I said to him, look, I'll do a white paper for you, but I'm really not interested in just doing a white paper. If there's, you don't know me, I don't know you, you don't have to promise me anything, but let's just see what the possibilities are.

And about two weeks later, I called him, and I said, I've done the white paper. I think that there are possibilities here, but I think that we need some tweaking and certain things we can add, and there's a common theme that we can use for this actually. And he said, okay, email it to me.

I said no. He said, I said, do me a favor, get all your guys together. I'll come down to Carlsbad and I'll talk to you about it. It's so much better that, having another, and that's what I did. And that turned into a four hour lecture and I said to them, and that's where we laid the groundwork for this extracellular matrix remodeling, all based on wound healing.

And the TriHex, which is the tripeptide one, and the hexa peptide 12 said, this would be excellent in terms of preparing the extracellular matrix. And I gave the background there. And and by the time I was finished, Scott said, okay, what do you want to join us? And I thought I'd just start as a simple sort of one, once a week I'll stop in, I'll see how they're doing and I'll advise them. And that, that pretty soon changed, in the first six weeks I realized now.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

And that's 2015?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

In 2016, by that time end of 2015. And more or less when Diane joined as well. And we beca, we formed a really nice partnership at that stage and which has been, steady ever since then.

And they gave me, which I really appreciated, wh when we started with the nectar, they gave me a free reign in terms of the science after that and said, okay, this looks like it's an interesting narratives. The dermatologists and the plastic surgeons seem to enjoy that. And when my colleagues have a good news sexy sign story to tell, there's nothing that.

Them more. So that was terrific. And this was a new kind of area that we're delving in and a new story. So that became really attractive, for them. And and then we started as, developing the products down the line based on the same sort of waste product prepping the skin, prepping before you did anything.

And there's a lot of stories, to that as well. So that's how it started.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

I want you to take us through a few of them. So we've touch, touched on the in the TriHex peptide and it'll come up again. I know, but why don't you take us through say Enhance. There's, so you did change.

That was a pivot, if you will. In terms of swelling and bruising. And up until then, we had Arnica and a few other things topically and orally and so forth. But why don't you take us through what you were thinking when you came up with Enhance. I think it's really quite remarkable.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

Just to take you back a step, granted the time there was a really big niche in procedure related topicals. Why was that? Because that for example, with skin resurfacing, if you did an ablation that was fairly deep, the skin was very vulnerable. And we were using very bland ointments at the time. Petrolatum and things. And particularly it was bland because you didn't want, that skin was vulnerable.

You don't wanna, you didn't want to introduce an active that we'd. Had the possibility of an adverse event. So there were very few on the market that were successful. And I know that people said to me personally, you're crazy to get into that, that period of time because their skin is so vulnerable and you don't want to take chances and you're gonna have bad luck with adverse events.

And I decided that. You know what, this is a really nice area to get into, and we'd all discussed that. And the other area was the preconditioning is prepping the skin beforehand.

And a lot of that was really based on wound healing because many years ago when growth factors, black platelet derived growth factor came out, and we thought we were gonna use this for diabetic foot ulcers, we realized pretty soon that if you put it on without preparing that wound, it just disappeared within minutes because the wound over time and the products of metabolism had collected and you had enzymes and corrosive enzymes within this exudate that ate up whatever you put in there.

So it was a waste of time. But if you prepped it beforehand, so you cleaned it, you got rid of the inflammation, you put it under control, you try to stimulate some epithelialization, and then you put your product on.

Chances of success went up exponentially. So I looked at the skin and said, you know what? We've got a chronic wound. I'm not the first one to suggest that, the skin, we've been exposed for years and years to the sunlight, to photo damage, to wear and tear from normal sort of day-to-day living.

And that's a chronic wound. So what are the products of metabolism that collect there? We knew what they were in the chronic wounds, generally in infectious, a diabetic wound, but what are, what collects in the skin with time? And we started defining that and realized that collagen broke down. There were fragments, elastin broke down, there were fragments.

We had glycation end products from circulating blood sugar. That also created a stickiness in the extracellular matrix. And we soon realized. In that dermis, which is the important part of the skin, we should have a constant dynamic conversation going on between the cells and the proteins, which are the collagen and the Alastin.

And that was not happening because it was getting clogged up by all those products of metabolism. So the first thing we looked at was trying to clear that, let's clear that. And then net stimulator replacement for that with collagen and elastin. And we managed to do that with a nectar, and then at the same time with a nectar, because it was being used with ablation and there was a lot of inflammation.

We added elements that were going to decrease the amount of inflammation, et cetera. So you talked about enhanced, but really the general theme there was get rid of waste products. Okay, so the first waste, that's the prep part. Exactly. That's the prep part.

Prep the extracellular matrix. And when that became successful and we saw, cuz we first did gene expression and then we did biopsies and we made sure that everything was very well validated. And then when we saw, and it surprised us that in a matter. Two to three weeks, we could see a change in that extracellular matrix.

You were taking the old out, replacing it and replacing it with a new, so that whole concept for waste products was working really nicely. So we said, okay, we've developed this. The next step is maintenance, which we did as well. But then after that, if we're in devices and we're in that area of procedures.

Let's look at the other devices that create waste products. And the first most obvious one there was cryolipolysis that was being done. Non-surgical fat reduction. Being done extremely commonly. What was the waste product? We were actually intentionally injuring fat cells there.

And they were going through a process that we call apoptosis, programmed cell death took a long time, but when the fat cell died, it sped out this lipid droplets and these lipid droplets were very pro-inflammatory. So the first thing we investigated is, can we get rid of that, waste those waste products in the form of lipid droplets, get the macrophages, which are the vacuum cleaner cells, to get that to stimulate clearance much quicker.

And we found a way to do that, and we found a way to get it down and we did delivery mechanisms. So, to a long-winded answer to your question...

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

No I'm glad! So you're right now at Transform. So yeah. So let's stay, let's spend a few moments on Transform. I was gonna get to there after Enhance, but as long as we're there at Transform, because I was a part of that study.

Also, and I saw clear cut differences of both when before we started the real study on the admin. Then when you started the study in the arms, it was so obvious. The difference of the ones that were treated versus non-treated and again, most people were very skeptical, correct? They're saying, you what? You rubbed this cream on my arm and I get skinny?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

And your cream that you're rubbing on the surface is gonna get right down into the fat area so we went through a whole number of steps, and that's why I'm mentioning Transform first, because it was transformative if you want, in terms of the science.

Okay. Because basically what we did was number one, We found a way to stimulate those macrophages to eat up the excess waste products a lot more efficiently. Number two, we found a way to encircle it in a liposome. Now the peptides are very nice and predictable. They're small molecular weight.

They're 800 to 900 Daltons. You can get it through the skin pretty efficiently, but we wanted to get it through fast. When you did the procedure, we wanted this product to start working straight away. Okay, so we wanted to get down the hair follicle. Surrounded with a liposome. Anything less than three 50 nanometers, it goes right down the hair follicle.

Okay? So we designed a liposome. What's a liposome? It's a covering that you put over the peptide that can change its form that can get into niches and crevices very easily. And if you make it 185 nanometers, it gets straight down the hair follicle into the base under the hair follicle, and immediately under the hair follicle is an area called dermal white adipose tissue, which is fat, and that sits on the subcutaneous tissue.

Okay? So we had a shortcut you put it down on the surface, go straight down the hair follicle gets into the dermal white adipose tissue, down to the subcutaneous tissue. So that's the second shift in terms of, okay, first we can get the macrophages to work more efficiently, but how do we get it down right now?

We've got a way to get it down there. So all of those became steps in terms of waste product management, in this case, the fat. So that was the stepping stone. We managed that. We did the clinical trials that you talked about. We did the non, you know we did an upper arms, we did in the abdomen.

We had a beautiful way of validating now with photographic equipment that could show you volume changes. So we were able to validate it really nicely and we said if you can do this with fat, can we do this with red blood cells? What happens with bruising? This has been a product a problem that we've dealt with for so many years.

That the bruising and how do you speed it up and how do you make it less obvious? This is the same story cuz your red blood cells escape outta the blood vessels into your your extracellular space. Can we do something to speed up the process? So we found a way of speeding up the macrophages.

We used the same sort of story. It's a concept called autophagy, which is auto- phagy Auto, the body doing, phagy, devouring. And the Nobel Prize was won in 2016 or 17 by a Japanese scientist that really described this. The body has a way of getting rid of these waste products. If the cell is not badly damaged, this autophagy process will help to actually let this fell survive.

It'll bring nutrients into the area, but if it's badly damaged like we see with cryolipolysis, basically it'll repackage these areas into smaller areas and stimulate the macrophages to come and get rid of this. And we found a way with our peptides and our gene expression to stimulate that autophagic process.

So we did that for fat. Now we are going into red blood cells. And with the red blood cells we used an. Extra sort of component called lactoferrin, which is an iron absorber. So now we could actually absorb the iron, we could absorb the red blood cell particles, and then at the same time we wanted to decrease the swelling.

So really without going into a huge amount of different science, the common theme here, which is new and different. Is this waste product management. And it's such an important part of it, and with tongue in cheek, when people say to me, what are you know what area you're in? I say We're in waste management.

Because when it comes to when it comes to skin health, And it comes to general health. If you look at Alzheimer's disease, for example, there's a, there's beta amyloid that accumulates. There are a whole lot of waste products that really cause and aggravate the disease. And the same sort of story is true for skin.

So we've had this by using this kind of concept and partnering with different devices and different procedures, we found a way to actually get into a whole new area. Get rid of those waste products a lot faster. And everything really is optimized after that. So they enhance that. You talked about that's a product that we use with injections.

Yeah. So for bruising, for swelling, that's really good. It gets the makes the bruises disappear really quickly. And by the way, to validate, bruising is a whole nother. Because if you look at the literature, short of dropping weights on somebody or shooting them with a paint gun there's very little that you can use as a model.

So we're headed to develop our own models for that. We're headed to develop in vitro models. And so that all became a common theme, and I'm happy to say with all the clinical trials that we did, and now it's been on the market, all these products for quite a while that's been a really major breakthrough.

And then the next area as a plastic surgeon for me, and for you, in terms of. Thought if this is working for nonsurgical fat reduction, what about invasive surgery? Because we are also, we with our liposuction and with our dissections and our abdominalplasties, we really are interfering with the fat area and we are releasing a hole at lipid droplets.

And when I started looking at the science of the lipid droplets, it appeared to. The lipid droplets being so inflammatory, we're causing a lot of the induration and the swelling and the edema that we are seeing post-surgery. And a lot of the patients, complain of fibrous banding, in other words, discomfort for a while until they can get mobility.

And that's really internal scarring that changes. But can we speed that up? And and so that was the latest one, and you were involved in the trials as well, is in terms of invasive, let's precondition these patients beforehand, let's apply this reform and repair, which is the new product. But I combined what we had learned from the body product.

I combined what we learned from Enhance. So bruising, swelling getting rid of the fat droplets earlier. And then the nectar in terms of preconditioning. So putting that all together, plus adding a component for scar control and making that into one product became a very natural, logical next step.

And that's where we are. And I'm really excited about this because reform repair before major surgery, as inversive surgery, you start two or three weeks before prep it in the area that we're gonna be operating on immediately after. Same story. Put it there. You can put it directly on the scar.

And it covers that entire area. And we've just finished this sort of multi-center trial, which was really exciting because the biggest advantage was that fibrous banding. And that was the area that I was most keen on trying to reduce. In other words, 46 weeks down the line, these patients are so much more comfortable because that scar tissue inside dissipates really quickly.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

That's fantastic. So you've obviously come up with a lot of different solutions and your efforts to be the garbage truck, sort of clean up all this. And lately we've been seeing a lot more of this regenerative medicine. Everywhere we look at the different meetings, it's exosome this, exosome that.

Can you tell me about your thoughts about exosomes, both today and also in the future? What role you think they may be playing in skincare and restorative health?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

Yeah. Exosomes it's a very interesting concept and it's very exciting when they discovered it. And these are small particles that the cell gives out.

It's a sort of communication, a way of communicating cell to cell, okay? And they're different sort of sizes of these little particles, but what they've discovered is that the particles could exosomes contain miRNAs, lipids, and protein. And those are instruction molecules telling the next cell what the status of the previous cell was, what we need to do, what, what's needed here, what, so the signaling mechanism is really elaborate in the tiniest, tiniest of particles.

So if you can get to that and you can understand the conversation. Then you can actually include parts where you can control that conversation. Then you're gonna change the whole network of cells and the way cells behave, which is so exciting. The problem is that at the moment now, the exosomes contain so many different particles that actually controlling that conversation is really difficult.

And one of the areas that I've tried to veer away from is using for our skin management is using. Growth factors, biologics, stem cells, exosomes, because there's a whole area of unknown about them. That there's certain things that we know, but there's certain things that we don't know. You need to be able to get from each batch that you produce consistency, which is very difficult when you're looking at biologics.

You need to have predictable behavior from them, which is really difficult. So from that perspective, peptides were really attractive to us. Synthetic, we knew what we were getting. We could measure the ex, the gene expressions and everything. And we, it was very predictable.

So take that same concept with exosomes. What excites me about that and nobody, there's one scientist that I know at the moment that is doing this for me, the most exciting part. Is seeing if we can define the indication that we want for that exosome, and then take that miRNA and the protein and the lipid that was part of that exosome and create it synthetically.

Create a synthetic exosome. And I can see that's a new sort of concept. It's a new concept to most people. But there is one scientist from the Max Plank Institute that I spoke to that has started doing this. And for me, that's the exciting part. Why? Because then you hone down on exactly the indication that you want.

You've got your standardization, you've got it. Off the shelf. Now the other thing about exosomes, which is interesting is it doesn't have the same sort of immune reaction. So you can use exosomes off or off the shelf, but if you use a synthetic one, you cut out all the background noise that we don't really understand and you stop all the potential for this.

Being tumorogenic and all the things that we are scared about in terms of exosomes, and you're honed down just on the indications you want. So what excites me now is we're at a perfect storm where you have molecular biology, genetics, biomedical engineering, a whole lot wearables, the technology for validation.

All of these have just gone up, exponentially. And for me to be able to create biologics, like exosomes stem cells will look at the secrete terms. In other words, what is secreted by the stem cell rather than using the cell themselves. And if we can produce those synthetically, that for me is where the future lies with this.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

That's very interesting. So is it true that if I were to take my platelets and someone were to get my exosomes that my exosomes could be injected into you or put without having an neurological reaction.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

And you mentioned platelets. Cause that's also quite an interesting one. And for me that's even more interesting than the others now because we're honing down on an area now. So regulatory-wise, it's a little safer here because we know platelets have got a restricted sort of action compared to stem cell exosomes, for example, where we, where there could be a host of different reactions that we don't understand.

Platelets a little bit more predictable. But the thing about the exosome is they, Carry the same kind of antigenics signals. In other words, the sort of rejection that you would get from normal cells that we'd use transplanting from one person to the next. Is not in the exosome, so it's immune privilege from that perspective, which makes it attractive as well.

The danger again for me or the unknown, We think we understand some of it, but there's no question, we don't understand a lot of it, so what's it gonna do? That we're not anticipating during that, and that, that's why I love this sort of way of let's see if we can restrict it in terms of where we want to go.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

In terms of their size, or the valency or whatever the do they have any problems getting through the.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

No, not really. Look this size is tiny, but what you'd have to do is someti, depending on the formulation that you're using and this goes with everything is you need a balanced formulation.

pH is sometimes important. Liposomes are sometimes important, especially to actually protect it. So liposomes are important in terms of actually delivering mechanisms. But they're also important if there's any instability or problem with the degradation of. Live biologic, then you would actually encircle it and encapsulate it to protect it and to get it in there. So there may be little nuances that you need to protect it. And to get it in there as well.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

Okay but I'm seeing more and more companies pop up with a transcutaneous or a lotion type of exosome delivery.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

Yeah. And I, I understand there, and it's exciting science, but I think that it's, we are not at the phase that we understand it fully yet.

And that concerns me a little bit in terms of, what we're seeing also, don't forget with biologics in order to keep them not as much with the exercise, but with cells and growth factors and all that to keep them. Stable and love. You need preservatives, a lot of preservatives. You don't need that with synthetics, with peptides, et cetera.

Okay. And preservatives are not that friendly to cells generally, so we want to try and stick away from that as much as we can.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

Could an exosome be dehydrated and then reconstituted subsequently? Is a non-synthetic exosome?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

Yeah. Yeah, to an extent. Again, all of those. In fact, and even in isolating the exosome, right in the beginning we had to use ultra centrifuges.

Nobody, very few people had the ultra centrifuges. Now there are other ways of doing it, so it's a little bit like battery technology is, it was so difficult to start with and there were so many problems until the interest level. Reached a certain crescendo and then all sorts of things came out. And the same's happening with exosomes now.

Different ways of isolated, different ways of using it. So it will be part of our vocab and be used in the future, but I think there's the tweakings that need to happen first.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

I'm sure you'll be right there at the forefront and I'll be watching you very closely. Now let's move over to Galderma. And Galderma purchasing Alastin. And then recently I heard that you are not only just staying with Alastin, but you're also taking another more extensive position with Galderma. Could you share any of that with us?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

That has not been announced quite yet. But let me just say that we are — we're thrilled to be part of Galderma.

If there ever was a partner that we could hone down and I'm sure you've chatted to Flemming a number of times and every second word of Flemming's is innovation or science, and that goes right down my alley. So we really got on very well. Because they're within big companies.

There's organic and there's inorganic growth, and most of the companies today are focused on inorganic. Inorganic being acquisitions. Let's acquire this technology. We won't do too much of the R&D in-house, but we'll acquire that because we'll get to the market a lot quicker. It's a lot more expensive, but we can get to the market a lot quicker.

But to be called an innovative company, you need to have. And my sort of area of expertise. And what I love doing is organic growth. In other words, in-house R&D is let's disrupt, let's try this. Let's do a moonshot, let's do something different in terms of looking at new technologies and new science, and see where we can go with that.

And Galderma has just increased the palette that I have in the and in the canvas every wall for me to really. Knee deep in it and they've also been extremely encouraging. So Atlastin, we are gonna continue, we've got exciting things coming up, but it also gives me a good opportunity with Galderma to look at not only aesthetics, but to look at some of the prescriptions to look at some of the cons.

Consumer, not everybody can afford the premium products that we are talking about today here. And if we, are the alternatives. Can we tweak some of the consumer products that are selling for 10 or 20 bucks? Add some, a little bit of science there that will actually make a difference and indications that will be really good for that.

So if the patient can't afford the premium product , we now have another alternative for them to go into one of the stores and purchase this unit at a much reduced price.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

Will you be staying at UCI?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

I, it's been incredible because Alastin encouraged me to stay. I was always concerned about that.

And Galderma again, have encouraged me to stay. Cause I think they understand that for me, to, again the best thing about learning is teaching, to be, to have more air on the ground there. And to be part of whatever is going on. We are doing so. Really great projects. We are doing ear cartilage framework, tissue engineering.

We are doing, excuse me, we're doing stem cell research based on fat grafting. We are doing areas like Dupuytren's disease that you understand where we are looking at fibrosis and converting fibrous tissue into fatty tissue. So there's so many beautiful areas that sort of cross-fertilize the way you start thinking that direction, you can automatically use that in other areas as well.

Sure. So I want to keep up the. Galderma have encouraged me to continue with that. So yeah, I will be continue with this. Good. I hope you do.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

That's great to hear that. They're not gonna make you move to Dallas or, oh, no. Something terrible. They're not gonna have Southern California. Nothing. Nothing against Dallas.

Yeah. But I know how happy you are to be in the OC. Exactly. And I'd hate to see you uprooted. So you've been through a lot actually in a relatively short period of time when you really look at this, you were a plastic surgeon. You still are you're a professor, an academician and a bench research, clinical research, and you came over to the States and you've seen an awful lot, Alan.

It's pretty amazing to me in a relatively short period of time, you're actually, you look at the big picture yeah. And I can think I remember back in 15 and 16 actually. So I'd like you to look into your crystal ball and tell us all what over the next 1, 3, 5 years. It's very exciting.

Obviously you're right at the forefront. Of all this, so I'm sure you're limited in all the different secrets you can and can't tell us, but within the scope of what you can tell us what do you see in the future?

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

It's interesting and you talked about this, I've created a beautiful hybrid for myself, which I could never have designed, had I not been part of it.

In other words, you have to be here and you have to be evolving to be able to do this. And for me to have the academic side, the research side, the working with companies that are turned on by science is just a beautiful sort of area. And to match that, the perfect storm that I described earlier on in terms of genomics and gene and molecular biology and bioengineering.

And I work a lot with bioengineers. And Engineers just in terms of the wearables and the technologies. So I've hinted at that and I think that the next thing is that's gonna come is if you look at molecular biology, there's your synthetic exosome was talking about. If you look at engineering, you've got wearables now where they can use polyurethane form, which is like glad wrap with sensors in.

You can put it on here and it can. All sorts of things. So we'll walk outside there and they're gonna say, listen, your skin's dry, moist. You need to apply this too much sun, do this, et cetera, et cetera. You'll have a personalized way of actually working out exactly what is needed on the skin side gene expression with gene sequencing.

And now we have single cell gene sequencing that tells us a huge amount about the individual cell, which is different because with with genes and gene therapy before we, put a whole lot of cells in there and then work out with all these cells, what is it doing now you can take an individual cell and see what the signaling is there.

So single cell sequencing, huge story as well. Crisp be in terms of changing genes and altering the genes and looking at disease processes and being able to alter the DNA and. Putting that all together and being able to get consumers to actually have products that are sold over the counter that they can get really quickly with science that is related to all those areas that I've talked about, makes for a very exciting future.

In terms of that, what do I think is coming? I think a whole incorporation of all those areas is coming. We are gonna have wearables, we're gonna have products that are gonna be focused on what we want to do. We're gonna have personalized medicine in terms of some people need this product, other people need that product. So it's an exciting time, I'll say.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

That's very exciting in the field of aesthetics, but also medicine in general. Correct. It has been very exciting to talk to you once again and see a little bit into the future. It's certainly been a great ride for me personally, getting to know you and seeing that science can actually drive a skincare company.

Likewise. And not just marketing, but real science. I appreciate it and metrics, and I want to compliment you. What you and Diane and the entire Alastin team have done in five, six years is truly remarkable. And you've changed the entire landscape.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Alan Widgerow

I appreciate that and really it's always fun to be able to interact with you.

You've always been so enthusiastic about the science, so it's always a pleasure for me to be here with you. Thank you.

Unlocking the Secrets of Cellular-Level Skin Health  Park City

Dr. Grant Stevens

Thank you very much, Alan. Thank you. And thank you for coming up here. And I'd like to thank all of you also for joining us on this episode of The Technology of Beauty, where I have the opportunity to interview the movers and shakers of the beauty business.

And as you heard, today was no exception. Thank you, Dr. Widgerow. Thank you. See you buddy.

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