This nih-Harvard-Berkeley researcher tells all…
Transcript
Charles Runels: So, we’re honored tonight to be here with Kryz Bojanowski, Dr. Kryz Bojanowski, PhD. — who was the inventor of the patented ingredient that makes Altar™ cream what it is, that makes it not like anything else on the planet. So, thank you for talking with us Dr. Bojanowski. We’re here in southern California, and it was quite a journey. Two and a half hours for Dr. Bojanowski traveling to be here to talk with us about this cream.
Now, this cream came out of, not a frivolous project. I know that there was some study about how to treat some of the complications of diabetes. Will you just talk with us some about, what was the idea that prompted the development of the main ingredient in Altar cream?
Kryz Bojanowski: Yes, so, we started of by studying the diabetic skin as a model for accelerated aging. In the human body, the people with diabetes have an accelerated senescence of their skin, and it’s the perfect model to study the wound healing, because those people get wounds much more easy and it’s more difficult to heal them. So, me coming from a perspective, from a background of studying wound healing and skin vascularization, I was compelled to develop a product which would help skin of diabetic people, which will translate into an anti-aging product in general.
Charles Runels: Talk to us more about your background. How were you educated and how did you come to be studying this process in the beginning? What’s your story?
Kryz Bojanowski: Well, it started once upon a time, I was studying molecular cancer from oncology and my PhD is in molecular and cellular oncology of cancer. I spent 6 years in the University of Paris, studying the processes which are related to development of cancer, to regenesis, and how to control those processes. This brought me for postdoctoral training to Harvard Medical School, where I continued this cancer research. I specialized most in skin cancer treatment, and finding new treatments for skin cancer.
From there, when I moved to California, I worked at Lawrence Berkeley National Lab for some time, studying genes especially, and cancer cells, normal cells, skin cells, and from there it was only one small step to really getting involved in the wound healing, in the skin regeneration processes, which basically implore the same mechanisms than cancer, actually, except that it’s for a good purpose as compared with cancer which are suppressed, and out of control.
In the wound healing, in the skin regeneration processes, those are controlled processes that the body controls better if you can put it on the right direction. So, I was fascinated by this apparent parallel between wound healing and cancer. I wanted to understand what are the differences which make them, so similar yet so different, and different outcomes. We found out that there’s a big need for compounds which will accelerate wound healing, and which will accelerate the skin regeneration, either with, or even without wounds. In diabetic patients, people have wounds, but even without wounds, their skin is deteriorating much faster than in normal people.
Charles Runels: It’s easy to tear?
Kryz Bojanowski: It’s easy to tear, it’s easy to get some micro crack, which will develop in the hard to heal process. We were looking for a compound which can, first of all, prevent this from happening, because, you know, prevention is very important. It’s much easier to prevent than to treat what’s happened. Yet, when the things really happen, how can we can stop the degeneration process? How we can stimulate the wound closure and healing?
We found out that there is a process called angiogenesis, which is growth of blood vessels, which is very important for the proper healing of the wounds. Diabetic people have a very poor continuous circulation, very often. This is a factor which place in the difficulty of their wounds to heal.
So, we looked for compounds which can support the growth of blood vessels, which can support the stability of the blood vessels, because blood vessels may be leaking, can be not strong enough, can break, can have hemorrhages. This is what basically happens in cancer, the blood vessels are very leaky, and this is one of the factors that I worked on, how to make the blood vessels more, in French you say, [French phrase], less prone to leaking.
Charles Runels: Okay.
Kryz Bojanowski: We realized that this can have a very important implication for healing of wounds, and for the skin regeneration in general.
Charles Runels: Right.
Kryz Bojanowski: When the density of blood vessels decreases in the human skin, and with this decrease you also get a decrease of oxygen being transported to the skin. You cannot evacuate the metabolic waste, the cells become senescent, and all those are factors which play a big roll in skin aging and in the ability of healing of wounds in diabetic skin, and not only diabetic skin.
So, we developed this product. You know, we screened a lot of natural compounds, because it was important for us that it was a natural compound. We had a kind of, what is called HTP platform [inaudible 00:07:29] screening platform, which allowed us to zero in, isolate a couple of [inaudible 00:07:38] candidates, which we then tested on several different animal models, enzymatic models. We grafted human skin on mice and we wounded the skin, and we looked how the skin heals the wound in the presence of our compounds.
Charles Runels: So, is that the platform you’ve referring to?
Kryz Bojanowski: Yes, actually, the platform is multi-level. First you have the screening platform, which is in vitro platform in the kind of 96, in 96 well agar plates.
Charles Runels: Okay.
Kryz Bojanowski: Then you select couple of compounds which are the best being the most hoped-
Charles Runels: So you have tissue growing on a plate? You have cells growing-
Kryz Bojanowski: We have cells growing on the plate, yes.
Charles Runels: Okay, beautiful. So they’re? Okay.
Kryz Bojanowski: Then you look at the processes which happen in those cells. You can measure those processes by measuring the expression of genes. There’s the technique of PCR, polymerase chain reaction, which was used for that. You can use enzymatic analysis, you can use immunoflorescence, you can use lot of techniques to zero on the compounds which are the most promising ones.
Charles Runels: Okay.
Kryz Bojanowski: So, from there you go to the next level, which is animal study. We use either genetically diabetic mice, which are genetically prone to diabetes, they develop diabetes after a certain time, or you can use immunodeficient mice, which don’t have their own immune system, so you can graft the human explants from the surgery waste material, on them, and then you can work on those human skin splat supported by the animal.
At the end you have the patients to whom we give this compound, and they put it on their skin. We formulate it, and they put it around their wounds, and that was the ultimate level of validation.
Okay, so after validating the most promising compounds in the cellular model, we transitioned to the animal model, and for that we needed grafts from National Institutes of Health. This is a very expensive study, it’s a series of studies. It requires sophisticated angle of strengths, which are genetically diabetic, or which are immunodeficient.
So, after validating the most promising compounds in those animal studies, we formulated this molecule, and we applied it to volunteers under the supervision of pediatric doctors or family doctors, or doctors who are responsible for patients with diabetes, ‘diabetologists.’ They gave this product to the patients to apply on their skin, and around their wounds. We did several types of measurements. We measured the skin oxygenation, because this was the most important thing that we were looking for; whether or not this cream allows a better oxygenation, better vascularization of the patient’s skin. We measured the transepidermal water loss to see if the barrier function of the skin is improved with this product. We measured skin elasticity, and what else? The skin thickness. All those parameters turned out to be increased by the application of the product after 15 to 30 days.
So, the skin was more elastic, the skin was more oxygenated. We used a very sophisticated partial oxygen pressure meter to measure the oxygenation of the skin. The transepidermal water loss was decreased. So, we got all the parameters improved that we were looking for. Then, and only then we decided, okay, this cream, maybe now, put forward to see the world and to be commercialized.
Charles Runels: Beautiful. So, that whole process took how much time? From the time that you started testing on the plates, is that where you would mark the beginning? Or before that? Before that you had to think about what to put on the individual plates.
Kryz Bojanowski: Yes.
Charles Runels: How did you come up with the list of the things you tested?
Kryz Bojanowski: Well, we looked mostly for compounds which make up some merit, or make up some hope to improve the circulation. This was not a very kind of straight forward thinking, because when you look for skin products and skin additives, you don’t really think about the circulatory system more about your epidermis, dermis, keratinocytes, fibroblasts, skin cells. But here we actually took a more kind of holistic, more wholesome approach and we looked for compounds which may be beneficial for the blood circulation in general.
Charles Runels: Mm-hmm (affirmative)
Kryz Bojanowski: And so we looked for medicinal plants which have some track record of benefit for heart, for blood vessels, for bleeding, things like that. So one of those compounds turned out to be isolated from a Chinese medicinal plant called Angelica sinensis, which is considered in Asia to be like an equivalent of ginseng usable for the female part of the population.
Charles Runels: Mm-hmm (affirmative)
Kryz Bojanowski: And I learned that actually this compound and the plant where this compound is prevalent is taken by one who have a prolonged menstruation which cannot be easily naturally stopped, they continue bleeding and so we rationalized that this bleeding may be due to the fact that the blood vessels cannot be sealed, cannot be healed. And that’s why the bleeding continues.
So we were looking for a compound which is going to make those blood vessels stronger. So I immediately thought this may be a good candidate for our search. And indeed, we did our first studies on the micro-circulation in vitro. You can make a kind of three-dimensional network of blood vessels, using capillary blood vessels which you can make. But after a couple of days, those networks, they are outside of the body, they will fall apart.
And so we use this experimental system to study those different compounds to find out which compounds can support this network, to extend the life of this network, make it more kind of robust. So this is how we isolated our most promising lead candidate. And from there we did these annual studies and then we get to formulate this compound.
Because especially for the skin care, the compound itself can be very good but if it does not penetrate inside the skin, it’s useless. So it also has to be not irritating because the kind of very nice compounds which work very very well in vitro, and in vivo when in animal models, but when the patient puts it on the skin says, “Ooh, it stings,” and it is not comfortable. And so it’s not going to use it even if it’s going to provide the patient with a benefit.
So we formulated this compound, encapsulate it in a way that it’s not going to make the skin irritant and it’s not going to make the compound irritant, it’s going to provide penetration into the skin. So these were all those factors which we had to take in consideration beyond the active molecule that we developed.
Charles Runels: So I think you just partially answered this question, but for example, you can have a foxglove that becomes digitalis [when you isolate individual compounds and concentrate them from the foxglove plant], or you can have [the leaves of the willow tree that become] aspirin. You can have natural products or you can have the distillate … what’s the chemical that becomes … yohimbine [becomes Yocon]. But then if you get a very discrete, if you get a very nice isolate of it, it becomes a prescription drug, it becomes Yocon, which they took off the market when Viagra was approved.
It was actually a very good drug because it was a very concentrated isolate of yohimbine. So back to this product, what is it exactly that you did that made that natural product become more medicinal, more concentrated, less irritating? Did you change it biochemically, did you capsulate it somehow? What did you do to it to make it more medicinal and less like the natural root?
Kryz Bojanowski: Right, yes, that’s a very good question actually, because the answer is, we did both.
Charles Runels: OK.
Kryz Bojanowski: So first we isolated some fraction of this plant, of this root. And we refined it to the point that there were only very few molecules and only the molecules that you want there.
Charles Runels: OK. By a distillated process, or how did you isolate it?
Kryz Bojanowski: It’s a multi-step process, mostly by chromatography,
Charles Runels: OK.
Kryz Bojanowski: By filtration,
Charles Runels: OK.
Kryz Bojanowski: By affinity chromatography,
Charles Runels: Yeah.
Kryz Bojanowski: So …
Charles Runels: ‘Cause this detail, sort of science, is the kind of step that you might … this is what you do in a day. But when people look at this product they might not have any idea what you did that took this natural root and turned it from foxglove into digitalis but so to speak metaphorically, you took a natural product and you turned into something much more usable and more effective.
So what you’re saying is by some multi-step, sort of through pass chromatography and some filtration systems, you took different chemicals that were in this natural root and you isolated a particular part of it that seemed to be doing most of the work, is that what you’re saying?
Kryz Bojanowski: Yes, yes. It was fractionation, which was based on biochemical properties of the different ingredients in the root…
Charles Runels: OK.
Kryz Bojanowski: And it’s called bioactivity-driven isolation.
Charles Runels: OK.
Kryz Bojanowski: So basically to start with, it’s kind of very difficult to isolate compounds from a botanical that you are sourced because it’s so full of molecules. Life is full of molecules. So we needed to design a method which would allow us to be guided by the bioactivity, to gradually isolate the less and less amount of the smaller and smaller fraction of those molecules from the root to the point that if you remove one it’s not going to work or it works less.
Charles Runels: Yes, so as simple as it needs to be with no more simple than that.
Kryz Bojanowski: Right, so it’s a kind of fine balance.
Charles Runels: Yes.
Kryz Bojanowski: So if it’s too much, you are going to tag along some compounds which may not be desirable.
Charles Runels: Yes.
Kryz Bojanowski: If you purify too much, you are going to lose activity. Because very often in life, things are happening well because of one molecule.
Charles Runels: Yes.
Kryz Bojanowski: Very often it is combined activity, synergistic activity of several compounds which basically make things happen. So our pharmacological approach to medicine is basically purify one molecule, make it as pure as possible, make it into a drug, which, intellectually speaking, no, scientifically speaking, is very accurate. But very often you pass, you miss some activities which could be much better if you could leave a couple of compounds together. It would be a not so much defined product but still very, very useful.
Charles Runels: OK.
Kryz Bojanowski: And so we decided not to go all the way to the pharmacological grade of our preparation, which would allow us to file NDA and get a prescription medication status because we would lose this, at least partially, this activity which is contained in a multi-component preparation. So we stopped at the kind of border between multi-component and pharmaceutical grade.
Charles Runels: So I’m taking it that you can test it both sides of that line to figure out where to stop, is that correct?
Kryz Bojanowski: Yes, yes. We of course did many isolation repeats. It was a kind of trial-and-error process and that’s why it took such a long time, six years, right.
Charles Runels: Yeah.
Kryz Bojanowski: So we finally ended up with this minimum necessary amount of compounds which are going to provide optimal activity for the blood vessel support and the skin regeneration.
Charles Runels: Six years.
Kryz Bojanowski: Six years.
Charles Runels: Yes.
Kryz Bojanowski: Yes. And it could have been much longer if we didn’t get the support from the government, from the NIH, so that was actually quite big support.
Charles Runels: Meaning that you had other people helping you with the study.
Kryz Bojanowski: Well, there was a funding from the National Institutes of Health because we also developed a wound dressing which is a companion to the skin care product. But also of course I wouldn’t be able to do it by myself, I mean, these scientists, they don’t work solo. They have teams. So I was fortunate enough to have a good team of colleagues and technicians who really put their energy and their heart into this project.
So once we had this multi-component botanical isolate, we needed to formulate it in a way that it’s not going to be irritant to the skin of the patients and which will allow the active materials to penetrate into the skin. And that was another challenge. It’s actually often underestimated how much effort has to go into formulation of those active materials for the skin.
So most of the skin care products, they are called oil-in-water emulsions. So basically you have the lipophilic compounds which are surrounded by the water like film. And we took an alternative approach. We actually got a water-in-oil formulation which is more difficult to make, which takes more effort and more research to standardize, but which allows you to have a kind of packaging which is friendly to the skin.
Because skin is mostly composed of layers, right? So you need a like packaging which is going to interact with the stratum cornea which is this upper layer of the skin, of the epidermis, to allow the compounds to be then kind of introduced into the lower layers of the epidermis and even to the dermis.
So this water-in-oil solution allowed first the oil to contact the skin and then kind of dissolve into the oil, lipidic membrane, and then allow to introduce the active compounds which are water soluable, inside a skin.
Charles Runels: So the oil acts as a carrier to allow the aqueous part to then penetrate behind it somehow, is that-
Kryz Bojanowski: Yes, yes, that’s correct.
Charles Runels: So what you’re describing now is the formula for what’s the other ingredients in the package, Altar™, is that correct? This formula for the water and oil is the thought process that went into the other ingredients.
Kryz Bojanowski: That’s right.
Charles Runels: Can you specifically tell me some of the things in the list that accomplish what you just talked about?
Kryz Bojanowski: Well, as you can see, there’s a lot of compounds.
Charles Runels: Yes.
Kryz Bojanowski: And there’s a story behind each of the compounds.
Charles Runels: Yeah.
Kryz Bojanowski: And so, for example, the Dimethicone is FDA approved skin soothing compound. There is a, how do I say… This is a very interesting compound between what we worked separately on and we found out that the hydrolyzed silk, basically it’s a protein. And this protein is very good at simulating collagen expression. Now we go back to the laboratory studies. One of the studies that we did is to assemble some of those components and put them on the skin and measure gene expression in the skin. Basically, by measuring the gene expression you have a genetic print out of the… You learn what is the genetic response of the skin to the formulation that you are planning. So this is also something that we did it, the time that we did it was very unusual to do, because you don’t look at 70,000 genes; that’s the amount of genes we have in our body; enough to formulate a skincare product, but we did just that.
We did what is DNA microarray study which allows to measure the expression of every single gene in the tissue. So in our case it was steep and we measured, we quantified the expression of those genes with or without our formulated product.
Charles Runels: With the hydrolyzed silk?
Kryz Bojanowski: With the hydrolyzed silk, yes. And we found out that hydrolyzed silk adds to the benefits of the angelica sinensis extract. So that’s what only some of those share but it’s a very good oil which provides an lipihilic kind of environment.
Charles Runels: So is that part of the care here you’re talking about?
Kryz Bojanowski: It’s a part of the care. It’s not just like two compounds that you would, it’s not like two level blocks that you put together. It’s more like a meshed entity. It’s a kind of integral structure which is formed between a few compounds which are towards the outside with the formula becoming hydrophilic when you get inside the formulation. The formulation you can think about, that’s about like liposomes or micelles and that’s like an ingredient of hydrophobicity from the outside to the inside. Different components occupy different layers in this grid.
Charles Runels: So I noticed when I use it, that it does have an exceptionally just smooth, pleasant feel to it. Is that what I’m feeling? That sort of lipolytic outer layer, the aqueous, what would you attribute to the fact that it just feels very soothing? Is that the whole recipe-
Kryz Bojanowski: Yeah, it’s like chef cooking a special dish!
Charles Runels: So how many years did you work on this recipe?
Kryz Bojanowski: Well 6 years of actual testing.
Charles Runels: Just on the one ingredient?
Kryz Bojanowski: On the one ingredient. Well we did it testing in parallel in several ingredients. So if you add all of the years of experience, of work on each of the components, it’s going to be probably close to maybe half a century.
Charles Runels: Are you half a century?
Kryz Bojanowski: Half a century?
Charles Runels: Are you a half a century old?
Kryz Bojanowski: Well that’s actually I am getting there.
Charles Runels: I think so to be plain that this is not a lotion that you cook up at the local dime store. This has a lot of thought that you’re allowing us to make it part of our procedure, because I think we have an amazing group of doctors working– we are now in over 50 countries and it’s about 2,000 of us–really brilliant physicians in multiple universities. And I’ve had a lot of people bring stuff to our group that I’ve said “no” to for 8 years. It went from nothing was good enough for us to now I’m actually honored that we’re able to offer this as part of our procedure, because I think it obviously it contains a big piece of the life of a brilliant man built into it. So I’m very grateful that-
Kryz Bojanowski: The honor is the product. I also feel that this product really fits perfectly into your strategy, because of it effect on the strength of the blood vessels; and also in the skin, the regenerative, the healing potential on the skin, which I think is going to be very well matched with your products. Which needs to be introduced by puncturing the skin gently and this product is going to allow those patches to go away in no time. I think it’s the perfect match.
Charles Runels: Yes! When we use PRP, we have biopsy studies that show the PRP causes neovascularization, fibroblast activity, and the idea that we now have a cream that does the same thing at the same time–it’s no wonder that we’re seeing really miraculous results. We have other procedures, other than facial procedures, that we’re doing. For example, we have a procedure where we use PRP therapy [Vampire Wing Lift™] to regenerate some of the appearance and the function of the labia and some of the sexual tissues. Anecdotally, some patients told me that even post waxing the labia using this has a calming effect and a healing effect. Waxing can be pretty brutal to the skin or just shaving. Post shaving the labia where the tissues are so fragile, using [Alter™] afterwards can have an amazing effect.
Just think about the drugs. You do thousands of test and millions of dollars; and you put it in the hands of the consumers, and they reflect back at you because there’s a sizable number of people using it, and then stuff you haven’t thought about starts to be known. It’s going to be fun over the next few years to see what happens when we put it in the hands of our providers and in the hands of thousands of patients.
Kryz Bojanowski: Yes, I feel like my baby grew up and left the house. I don’t have control of it. But it’s interesting what you said about the shaving; because it comes back to this idea of the female ginseng I think that in Asia, this plant is being used by the female population predominately. Maybe because there are some specific benefits to the gender.
Charles Runels: I need to be careful. I’ve been putting it on the scrotum and the penis. I just need to tell you right now. For me that’s important that that stays healthy too. If you’re gonna have fewer older cells, why not put it on your penis. So I’ve been putting it on my scrotum and my penis and I think its happier-
Kryz Bojanowski: Well it’s skin. You have skin, wherever you have skin.
Charles Runels: So this plant from which the isolate is made, are we going to run out of that? Where does it grow? I haven’t seen it growing… obviously it’s in China and it’s in other places. Are we going to say “oh this product is wonderful” then all of a sudden we can’t get the plant anymore.
Kryz Bojanowski: That’s a good question because I was referring to a female ginseng. It’s not like ginseng which you have to go to the mountains to hunt-
Charles Runels: Which I’ve done before. It’s very hard to find.
Kryz Bojanowski: So this one is actually cultivated. It can come from organic fields. So it can be certified organic. There’s a control over the supply. We don’t need to worry about that.
Charles Runels: Good. Glad to hear that. I’m really honored to talk to you. I think that’s all the questions I have for you. I’m going to invite our providers to write in and blog, and the people who use it, to let us know. Hopefully they’ll teach us more about your baby. What it could be used for. I do think it’s going to take a life of its own. I’m really grateful to you for thinking it up.
Kryz Bojanowski: So, I give it to you now.
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