LS 117 - Translating Research into Gene Therapies That Will Benefit Health Spans with Brian Hanley

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Hello everyone. Welcome to the Longevity and Biohacking Show. This is your host, Fernando Aries, in partnership with the Hartman Media Company. Today, it is my pleasure to welcome Dr. Brian Henley to the show. Brian founded the company Butterfly Sciences in 2009. Their purpose is to essentially do a translation of research into gene therapies to benefit healthspan, obviously a cornerstone of our show. Butterfly Sciences currently has a clinical trial in progress for testing a gene therapy in humans that has multiple beneficial effects and Brian will be talking to us in detail about this. Brian has an interesting background. It includes having written papers in biosciences, economics, terrorism and policy. He got his PhD with honors from UC Davis in California, starting with a degree in computer science. He's essentially a very interesting guy to talk to. He's a serious entrepreneur, has lectured for years to the MBA program at Santa Clara University, also in California, on terrorism and international business matters. So welcome Brian. It is a pleasure to have you on the show today.

Hello, Fernando.

So, Brian, where are you located? Give our audience a sense of geography. It's always interesting to know where people are calling from.

Sure. I'm in Davis, which is near Sacramento in Northern California. We're about 100 miles north of San Francisco.

Sure, yeah. So, Brian, let's get right into it. I just love the pitch you give for Butterfly Sciences. It actually reads as follows. If you want to feel 20 years old again and have money to invest in your future, let us know. Butterfly Science is looking for motivated investors who want to live longer, healthier lives. Well, that sounds awesome. I certainly fit the bill. Sign me up.

Write me a check.

So what is Butterfly Sciences all about? Brian, how are you going to change the world with your products?

Butterfeller Sciences does translational science, which means I'm not doing basic research. That's a very expensive game that. You need the kind of resources that Google has or governments have to really be in that. And it's impossible to predict what's going to come out of basic research. So what I do is I take research that's been proven to work in animals and try to turn it into a product that people can make use of and will benefit our medical system.

Now, you have a couple of, I guess, major areas that you work on. The first one is anti aging and of course, for longevity. That's a cornerstone, as I mentioned earlier, of our show. It seems to me that the research is pretty clear that it's all about that human growth hormone. And I know that this is a cornerstone of your company, but what exactly is, is your use of the human growth hormone? I mean, you talk about the growth hormone releasing hormone, which is ghrh, that's the acronym used. What are we exactly talking about and how is it used in your therapy? Can you just go over that?

That's a really good question. And I'll start by saying that in longevity studies in animals, generally speaking, lower levels of growth hormone result in longer lifespans. Dwarf mice and other dwarf animals tend to live longer, and conversely, larger versions of a particular animal will have shorter lifespans. GHRH itself is named for the first thing it was found to do, and this is fairly common in biology. Another example is myostatin, which is a hormone that causes myosin, which is the muscle protein to to break down. Ghrh, like myosin, has other functions. Myosin has the positive function of upregulating tendons and ligaments to strengthen. This is one of the reasons why when people take steroids for too long, over many years, they will tend to weaken their tendons because steroids ramp up the follistatin pathway, which suppresses myostatin in order to achieve muscle growth, and that causes the tendons to not get their growth signal. GHRH has multiple other functions. There's receptors in the heart that organize heart muscle. There's receptors in the thymus and other parts of the immune system which improve immunity. There's receptors in the kidneys for proper kidney function, and there's receptors in the brain. It has a number of effects. Just one of them is to regulate growth hormone. Now, the regulation of growth hormone by GHRH is primarily negative in that if the GHRH level is low, then you're not going to signal to raise growth hormone to the maximum level that your body will normally support. However, if you give somebody a very high level of ghrh, it saturates those receptors. And growth hormone has its own secondary feedback loop that prevents it from getting out of control. You won't see the kind of bodybuilding effects that you would with direct injection of gh, where you will get extraordinary overgrowth of tissues, muscles, the gut enlarges, liver enlarges. There's a lot of secondary effects to gh. What you can do is get the growth hormone level up near the level that for example, a healthy 20 year old would normally have.

That makes sense. I mean, it's essentially you're trying to mimic that. One of the reasons why us as kids, as teenagers, as we're growing, there's lots of hgh, the human growth hormone in the body. And as we age, we start to lose the ability to produce these hormones. And by having a ton of them or helping our body increase the amount, we should go back now. Is there a limit on how long we can keep up with this? I mean, isn't there a time when, when the body just, just has enough? Or do you think we can keep doing this indefinitely?

Well, it's not going to be indefinite. I'm calling this a health span improvement because all of the, the animal data indicates that. And proving that something increases lifespan to any significant degree in humans is a really hard thing to do. It takes a long time, it takes a very large number of people. It's very expensive and difficult to do. It's hard to do in animal studies as well because there's so many other factors that relate to this. I have an article I did on that on IEET.org called metformin, gamma Rays or Chocolate. And what it goes through is it talks about the differences in lifespan extension from different things. And I chose three different things. One was metformin, one was gamma ray irradiation, and the third was a chocolate supplement called Actycoa. And all three of them on average do roughly the same thing with probably the octocoas, maybe a little better. That's based on large numbers of studies. Only a few studies show really large increases in lifespan, you know, say 20% from metformin. Most of them, if you take the mean of all the studies that at least I have on file, it's about 7%, which is something it's certainly not, probably not going to do harm. But when you start trying to apply that To a human population. People, well, people aren't mice. We have many different lifestyle factors that matter. There's a number of factors that are, that have been shown to be strongly correlated with lifespan. Things like educational attainment. Being successful in your life is a significant one. Having a purpose is a really big one. People who have some who feel that they have a reason to be here will survive even in the face of incredible obstructions and you know, serious disease, sometimes for years. One of the most famous cases of that I think is Stephen Hawking. You know, here's a guy who's got a disorder that should have killed him many years ago. You know, he should have been been gone 40 years ago. But he became valuable and he knows he is. He has a very strong purpose.

Exactly. I agreed 100%. I think that purpose is what he still has contributions to make and he knows it and that's what keeps driving him. I was commenting earlier, that's a significant improvement. When you look at, you know, 7 to 20% in health span, you know, that's important. You're talking about health. When people talk about aging and not having health, not having a health span along with a lifespan and that's as I mentioned in the beginning of the show, that's a big difference. You want to live longer, but live a healthier life. Brian, what is the business model for this particular anti aging therapy? Are these available to consumers now or when will they be and what do you think the cost is?

I have an IRB review coming up, which is the first one where we'll start talking about whether they would approve expanding this. The data is looking really good. There doesn't seem to be any major adverse effects. The one adverse set of adverse events that can probably be called an adverse effect is that I have re injured four significant injuries that I had from when I was younger pretty seriously. And the reason is that I, you know, I've been feeling so good and pushed and, you know, competing with 20 year olds, that sort of thing and overstressed the, you know, connective tissues that just weren't up to it because I didn't take it easy and I didn't take it slowly enough. But aside from that, there really isn't any that seems to be negative given the current progress.

What do you think is the timeline?

There's a couple of different ways this can go. The way I would prefer to do it is to get the funding to do a standard clinical trial where the company pays for everything. And you know, we take around five years to go through phase one and phase two. Phase one being safety studies and phase two being efficacy studies on clinical targets like congestive heart failure, immune system depression. There may be an application to arthritis, certain other things. That's the way I prefer to go.

Okay.

However, that's very expensive. That whole course is on the order of $20 million. And the other way is to put together a self pay clinical trial where people would have to pay for it themselves and you know, that would be thousands of dollars. Just the following, you know, the assays that I've done to follow over the last couple of years have been on the order of $10,000 just for that. So we can cut down on that and you know, and simplify that course. But it's still, you know, it's pretty expensive to do and it will be a, you know, it'll be a significant cost to people out of pocket.

Sure, yeah, sure. Now Brian, let me switch gears a little bit and we talked about anti aging. There is another aspect of the therapy that is related to HIV aids, the synthetic vaccine system. Can you tell us a little bit what that is and how that is going?

Sure. Well, that's where that, when I started I thought that that would be the best clinical target and that it would be well received. What that therapy is based on is that there's a protein on the surface of HIV viruses called GP120. And GP120 as it turns out, has a very high affinity for ghrh, which means that it will act as a molecular sponge in the bloodstream. When people get into the later stages of HIV AIDS, their viral loads are between 500,000 and a million copies of the virus per milliliter of blood. You do the math on that. And that's a huge amount of molecular sponge to remove circulating ghrh.

Sure. Yeah.

GHRH doesn't tend to last long normally anyway. Its half life in the bloodstream is on the order of 8 to 12 minutes. So it's normally present in pretty low levels. And so I thought that this has to be a significant piece of the crash that happens in later stage eights. It's definitely not the mechanism. I don't want to give anybody that idea, but I think it's a significant piece.

Sure, I can see that.

So it was intended to address that.

Okay.

And then the other part of that was there is a molecule in all cells called TRIM21 which attaches to the FC chain of antibodies. And when it attaches to the FC chain of an antibody that is attached to something Else that causes a mechanism called ubiquitin elation. There's this molecule called ubiquitin. It was called ubiquitin because it's so common. It's a significant part of the proteins in any cell. And ubiquitin gets attached to something and when that happens, that something gets routed to this molecular garbage disposal called the proteasome. It's a cylindrical molecule that literally takes other molecules in one end and just breaks them up and spits them out the other end as little pieces. And this is the intracellular part of our immune system. So my concept was to create what are called micro antibodies. Camelids, llamas, alpacas and camels have a population of antibodies that have a single chain for the attachment part of the antibody. And that makes it easy to use with molecular biology. Whereas all other antibodies use two different protein chains to form the attachment site. That has been a serious problem in molecular biology of antibodies. The idea is to take a recognition site for the hiv, for the various HIV proteins and put an FC chain on it and then using gene therapy, get those into immune system cells and if they're either infected or an HIV virus attaches to them, those antibodies will destroy those viral proteins and essentially that cell could potentially be infected but still not show the effects of that infection.

Right. Well that is very promising.

There's some other methods that you know that have been proposed like and somewhat tested, such as RNAi, RNA interference and that sort of thing. And any one of those could be.

Done as a comparison to the, what we talked about anti aging before. So for HIVAIDS they follow the same phase timeline or do you have a different timeline for this portion of the therapy or is it all combined?

Well, what I did, I put that on ice because to do the antibody part is fairly expensive. And I had already gone and done a. Initially I came in and developed some assay methods. I thought they were broad enough and good enough that I license them. And part of that included creating some protocols for creating specialized antibodies and that sort of thing. So it already already spent a bunch of money on that. And as it worked out it I wasn't able to license those. It's really quite hard to license intellectual property. So when I went to venture capitalists, one of them finally told me, we like this, we think it'll work. But unfortunately today people with AIDS is a very, very small market, so there isn't a lot of incentive business wise for this.

And there are already drugs that people take every day and this kind of thing would Be what's called the surgical model, which means you go and you treat something and then you don't need to do it again or you don't need to do it for a while. I would call it a quasi cure, potentially.

Well, I certainly hope that it comes to fruition. The aspect of having the body produce the cure to a lot of issues. There's a panacea there. I think it's very different than trying to treat symptoms. And a lot of what the medicine tries to do with the existing drugs is suppress the virus. In this case of aids, treat the symptoms. But the underlying issue, you know, at.

The end of the day, suppressing the virus. I mean, this is, this is an alternative method of suppressing the virus because due to the fact that the HIV virus infects the very immune system cells that are supposed to attack and get rid of it, it doesn't cure itself. And so this is a method, a potential method of control. I would not call it precisely a cure, but it wouldn't. It's not, it's not a method of control that requires taking drugs every day. And it shouldn't have the kind of side effects that exactly, drug cocktails have.

Exactly. Or if anything, you might have positive side effects because having more of that growth hormone in the body has other applications, as we discussed. So just seems like a healthier choice, you know, no pun intended, but that I would have chosen if I had to. Now, Brian, I know we only have a few more minutes. I just want to ask you, what's the future like? What are the directions that your company is going to or you see the industry going to future applications? We talked before the show started about settlement of other planets such as Mars and applications related to that. That sounds very intriguing. What do you have to say there?

We can't deliver these therapies yet, but there are things that we know how to do now to, for instance, make a person's muscles grow to near their maximum size without having to do much exercise. And if we were to give that to, say, you know, somebody who went to Mars, it should make it much easier for them to return. Because somebody who is muscular and fit, if they go on 100% bed rest in the early stage of that, they can lose 4% of their muscle mass per day.

That's amazing.

This is a major issue on, you know, on the iss. It's why the astronauts have to have to exercise every day. It'll be an issue on, for people who go to Mars as well, because it's only 1/3 of Earth's gravity. So their bodies should adapt to that. And in a couple of years, that could be a pretty major adaptation. It could be really difficult for people, people to maintain the kind of muscularity that they would need to safely come back. So that's what, you know, that's one kind of thing. And we could test that here on Earth. I'm sure there would be happy volunteers. And the effect of that particular gene therapy in animals was to also, as a side effect, increase their lifespan by 20 to 30%. And they remained strong for their entire lives. There's others that could potentially do which could make people extremely radiation resistant. When I say extremely radiation resistant. The LD50 for an adult man who gets irradiated with their whole body with Gamma Rays is about 4 SV. There are ways that we have learned about to increase the radiation tolerance by a factor of more than 10 with some fairly straightforward super expression of DNA repair. And then melanin as well. Melanin is. And potentially because there is an organism that has been found here on earth, it was found inside the Chernobyl reactor containment in the dark, that lived on gamma rays and got energy from it. And the way that it gathered the energy was by super expression of melanin. It also had excellent DNA repair.

So when you say lived on gamma rays, it actually literally, that's all we had as energy to eat.

Yep, that was a significance part of its energy. Suppose it's kind of like ultraviolet light. You know, it's with trees. But ultraviolet light doesn't penetrate. So in theory, you know, one of my more out there kinds of designs is that in theory, you could create a human being who could live in an environment where you had thousand sievert or more per day. And they wouldn't just survive, they would thrive in that.

Amazing.

Because gamma rays are a form of radiation that would penetrate entirely through the body. So you'd be able to get get over the tree problem, which is, you know, with plants you have to expose some surface and you'd be able to do it on every cell.

Wow.

So there are potential, I call them the Marvel comics kind of things. There are potential gene therapies and changes we could make which could give people capabilities that are, well, not quite at the level of, you know, Marvel comics superheroes, but getting close.

They'Re closer to that than they are to us.

Sure. Yeah, I can see that.

I think there's people who would find that really something they'd like to do.

Amazing stuff. That is unbelievable. Well, Brian, I do want to give our audience any links, any additional information that you might want to share so they can follow along with your work. So please give out any URL's you can think of and any last thoughts before we wrap up.

The company website is bfsci.com there's a kind of a blog on there, but it's not terribly active. The kinds of things that a company like this does move really quite slowly. This clinical trial with one person, it's going on two years now, done some writing which is on ieeet.org you can, you can Google that with Brian Hanley, my name as the author. And you'll find some articles that I've written on, you know, on various topics to do with gene therapy and longevity and that sort of thing.

Excellent. Brian Henley from Butterfly sciences. Again, it's bf-sci.com oh, Brian, again, it's been been a pleasure having you on the show. I look forward to talking to you again in the future. You have a great day. Okay, sure.

And I am actively looking for the kind of investors who want to carry something like this the distance.

Well, I'm sure some people in the audience might think this is very interesting and might be contacting you, so I do appreciate that, Brian.

Okay, thank you.

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