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Gene Therapy

Fighting Aging With Gene Therapy: An Exclusive Interview With Liz Parrish, The Pioneer Who Wants To Keep You Young

Posted on 25 October 2015

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Liz Parrish isn’t your average CEO. A passionate advocate for change, her company BioViva is leading the fight for healthy longevity with pioneering gene therapies targeting Alzheimer’s, sarcopenia and even aging itself. Parrish dreams big, but she’s a woman of action. She’s even demonstrated her commitment by testing cutting-edge therapies on herself. Could her efforts change how we think about aging? Is gene therapy the future or are we moving too fast? We caught up with the woman herself to find out more.  

Let’s start with the big news. BioViva has treated its first patient. During your Reddit AMA we found out this brave soul was you. Being patient zero is extremely commendable. What made you decide to put yourself forward?

For me it was an issue of ethics. As we started to publicise what we were doing a lot of volunteers came forward, but it didn’t sit well with me. I felt if I was going to lead the company and say “we’re here and we’re going to do this”, it made sense that I came up and actually got behind it 100%. It didn’t feel like an option, which is why it does not feel exceptional or brave. I’m just an average person. It was the right thing to do.  

A great deal of science in the past has been forwarded by a certain amount of self experimentation. Is it an under-appreciated aspect of science?

We have become a very risk adverse society.There are dangers with any new technology. Even if there isn’t anything wrong with a therapy, the patient might be too sick already to benefit. You can imagine if we moved forward with patient zero and something went wrong. It would have been devastating to me, the patient and the company, it was one reason why I chose to test on myself first.

Could you tell me a bit more about what two treatments you underwent and what procedures were involved? 

Yes. One was a myostatin inhibitor injected into my leg muscles. 4 muscles in the front and then the hamstrings. It is not painless, but not bad if this is a curative treatment. The hTERT telomerase induction therapy was used systemically and locally. When more comfortable methods are made, we will adopt them.

So you used an AAV associated viral vector for treatment. What does it target?

The great thing is you can use specific serotypes for different cells. This means you can target dividing as well as non-dividing cells. We opted for a broad spectrum treatment by using these serotypes.

An adeno-associated virus 2 capsid - the protein coat containing DNA

An adeno-associated virus 2 capsid – the protein coat containing DNA

Do you aim to move beyond treating the hippocampus alone in the brain? 

We should go beyond that region and target some of the microglia. That’s what we’re trying to do. We’re hoping when we give Alzheimer’s patients a similar treatment with a different delivery method we can target the microglia, which might clean up some of the unwanted accumulations. There is promising data relating to hTERT expression and Tau Pathology in Alzheimer’s published this summer (1). So, yes, I think we will have an effect on more than just one region. However, there are regions we want to target specifically for different purposes.

So you have a fundraising effort to treat microglia in Alzheimer’s patients? 

Yes, we’re really excited about that. If it is successful it will let us do things a little bit differently. We would make sure we had a review board with us and an FDA specialist so we can catalog the effects.

(Find the fundraiser here)

What else is in the pipeline? 

We are exploring a myriad of options and targets. We may eventually target paths related to metabolism or intelligence. I mean, believe it or not, those same genes have a lot to do with cognitive decline and neural regrowth. When I say stronger, smarter, and more visually acute it sounds almost frivolous. It may sound like something in the distant future, but actually if you are all of those things, it protects your life. It’s more than just looking or even being young from a biological standpoint. It’s also about whether we can be better in other areas that might help us make better decisions, so we don’t get hit by that train.

 Is there one specific treatment you’re particularly hopeful you’ll see bigger results with? 

I have high hopes for the telomerase induction. We believe the quantity of vectors used in the test is sufficient to yield significant results. Still, we have taken a cautious approach to this in terms of dosage, in order to ascertain what is safe. While we certainly don’t wish to waste resources and funds, we also need to proceed with this as carefully as possible.

In the best case scenario what sort of results are you hoping for?

Of course we’re hoping both internally and externally there are changes. I would hope there is regeneration: better organs, digestion and more youthful skin. I’m not sure that it will affect my eyesight, but we want to see improved cognition. We’re looking at biomarkers like telomere length, I actually have my Life Length kit right here next to me! Tomorrow I am going in for more tests. We’re also trying to bring more people on to do some further testing, including methylation assays on my cells, to see if they’re behaving younger. We want to see everything from visual markers to cellular markers. 

Telomerase extends the caps of your chromosomes called telomeres (shown in green), and enables them to divide without fraying. Credit: Blasco Laboratory

Telomerase extends the caps of your chromosomes called telomeres (shown in green), and enables them to divide without fraying. Credit: Blasco Laboratory

What kind of timescale are we talking about before you’ll have an idea of the effects and whether it’s gone to plan?

The myostatin inhibitor has been tested already. We should start seeing results around 4-5 months and peak around 8-12. Although we could extrapolate from the myostatin inhibitor, we do not know how long it will take the telomerase induction to begin working because no one has done it before. Slow and steady wins the race in these cases, if you saw an abrupt change it would probably be a bad sign. We want to see if it worked, then modify accordingly. We won’t know what exact effect we’ll get until we start seeing it, but if it’s a small effect it would be better than none. Then we’d know we really need to bump things up in the future and if people might need more of the therapy. If we see a good effect we’ll just stick there. If we see a massive effect and it seems overdone, obviously we will use less in future trials. This time we stayed on the side of caution. 

Are you interested in BioViva expanding to stem cell applications, or sticking with pure gene therapy? 

I could definitely see us expanding into stem cell work. Our doctor already has experience in this field. I think they’d be even more advantageous with ex vivo gene therapy, where you take some stem cells out, give them the therapy, then put them back in to target specific areas. I foresee a bright future for this sort of approach. Stem cells have shown regenerative potential in animal and human testing. The quality of cells, falling costs, and range of applications have improved dramatically in the past few years. A combination of gene and stem cell therapy could create a very potent approach to combating cellular aging and disease. We are keen to explore the possibilities of that given the opportunity. 

You’ve said before there’s no real safety and efficacy in medicine, that every drug is an experiment even after FDA approval. Can we do a better job at medicine? Could you expand on what kind of changes you’d like to see? 

We have to rethink how we are doing medicine and what safety and efficacy mean. We already have a lot of research that demonstrates great effects in animals, and some in primate and even human models. We need to really think outside the box, I think outside of the box so much that I can’t understand why other people don’t in this area! The regulation is stifling. It does not only cost companies money, but millions of lives. People should have access to promising therapeutics and they should have the right to decide what they do with their own bodies. They have a right to make an informed decision about their own health and well-being. 

I’m all for safety and efficacy, but safety, efficacy and a high price don’t have to go together. We can be more innovative in the US if it costs less for safety and efficacy, and it doesn’t have to take 15 years. Let’s say you’ve tested a drug for 15 years. That’s great, but what happens in 20 or 25? So that’s where these gene therapies come in; they could be potentially life saving and I think that a lot of groups just don’t work with them because they can’t figure out how to patent them. That’s a big mistake. It’s a mistake for the world. I think we can do the right thing, and make a profit while doing it. I don’t think that big companies would lose anything by quitting the game of withholding medicine, rights and licensing to other groups. If they stopped we could move forward faster and actually cure disease. 

So to some extent we’re already in a worst case scenario, with hundreds of thousands of people suffering daily. We should be able to take a risk if the alternative is dying. 

Right. Adverse drug effects kill tens of thousands of people every year. Gene therapy is known to have killed only one person. This is a tragedy, but this should not stop us from saving millions of lives in the future! 
Treatment was a choice and it was an easy choice.What if through one decision you save a person’s life? You may die doing it, but you might save someone else’s life, or a thousand, or a million. I would absolutely do it, and that’s why I did it. I don’t know what will happen to me, but I know what was going to happen to me if I didn’t do it. I know what my options were, and they’re not getting better despite this run to change the paradigm of how we treat illness. I can’t guarantee that any one of those people, even huge companies will be successful. 

Genetically modified mice expressing GFP - the green fluorescent protein

Genetically modified mice expressing GFP – the green fluorescent protein

You’ve described BioViva as a disruptive, tenacious little company before. What are your goals and hopes for BioViva in the recent future, say 10 years, if things go to plan?

Oh boy. 10 years? Oh what we could do in 10 years. In a decade we hope to be a household name, synonymous with compassionate care. In ten years governments may be purchasing them for their citizens. I think 10 years is a bit of a jump. We’ll be giving them before or around 40, but maybe 15 or 20. We need to give them before disease starts, so we want to be big. We want to have products anyone can afford. Maybe in 25 years we’ll even want to do something entirely different. If the powers that be make sure everyone can gets these treatments, we could do more interesting things like making your eyes purple and your hair green. Working on the fun parts of life! But not in 10 years, I think we’ll still be drilling away at this. 

How important do you think public money is, or will we have to rely on private funding? 

I think that right now private funding is integral. Certainly if we’re successful we can build a platform. We would like to be a springboard for other biotech companies. If we can get this platform built off-shore at a fraction of the cost, but to an FDA standard so everything is safe and effective and proven.

In a best case scenario with positive results, do you think it might initiate a big change in attitude? 

I really hope so, that was part of the reason to do it. I have a lot of friends in the industry but they just can’t find the funding, and what little they do get it doesn’t go very far. What we really need is an influx of public interest in this area. If we can achieve something, if we can show results, the SENS foundation, other foundations or larger companies will see the only thing we need is more money! They’ll see the population has gotten behind it. It’s so important people get involved and realise this isn’t science fiction. One of the most positive things of getting results is an influx of capital. That’s the sad state of affairs. The best intentions can only materialize through investment.

So there’s no shortage of brilliant scientists to do the research, it’s the money and the public attention that’s a problem.  Do you think the longevity community is missing that key part of the battle? Should we be trying to inspire people more and look outside the box, instead of focusing primarily on the science?

Yeah, I think there is a barrier. The spokespersons we have are all very good, but they’re busy trying to speak to researchers, and researchers will often fight with each other even if they agree on the science. They’re great arguers, right?  Medical doctors do not always keep up with the literature. They’re trained about the body and how to treat symptoms with the tools  they’re trained to use. Getting researchers to communicate with doctors is really, really tough. BioViva’s doctor is exceptional. Jason Williams actually reads research papers, but it’s very hard to find that. 

So where do you need to get consent from? You need it from the public, and all of our speakers in the past have focused on garnering acceptance from the research community. We have enough researchers and we actually have enough medical doctors, but we need a public mandate! That’s what I do, I’m trying to get out there, to engage the public to let them know this research exists. When the public get behind it legislation will change. The entire public image will turn around when it’s finally seen as the viable and possible science it is. 

Many people are simply not aware of ongoing developments. Part of the problem is trying to legitimise it, realising it’s not quackery talking about it?

The media has killed us. They’ve killed us with headlines. Cancer has been cured 100 times, and I remember hearing in the 80s that HIV had been cured twice. It’s getting even more fantastical as more companies get behind this type of research, the headlines claim it’s going to happen tomorrow. That’s when people glaze over even more. They think ‘oh, somebody’s going to cure this so I don’t have to pay attention’, and a cure never materializes. My company is running as hard and fast as it can to get results. That type of media would be fantastic, right? Human results and age reversal. I mean that’s worth going for, that’s what’s missing. 

How do you feel about transhumanism and longevity frequently being coupled together?

I think it’s okay to run in tangent and I think it’s okay to run together, but we need more of the world with us. Some of the world is still dealing with pre-industrialised problems, but cures for disease can be a solution for them as well; it’s not just a solution for industrialised countries. We need to work with all of the groups, and shutting anyone out is a bad idea in the long run. 

We need to keep it positive. Lots of people are talking about future technology waiting around the corner for, but it’s hard for the public to take the baby steps to get on board. Just getting them to think about curing biological aging seems like a huge jump. But we can show them the work that has already been done to get there, and how it is a realistic goal. It’s kind of like holding people’s hand and walking them through. Nobody just came up with a good idea on their own, they had to be told about it to make a leap. Then I think we can get the whole world will join. 

Gene editing techniques could enable even more precise therapy

Gene editing techniques could enable even more precise therapy

CRISPR technology is big news at the moment, what’s your opinion on it? Do you think that different regulations in different countries might also encourage more innovative approaches in say the US or Europe if that does happen? 

Yes I think CRISPR will be fantastic. Before it I think zinc fingers were great. We need to make sure the technology isn’t just owned by one group, so that you have to be licensed to do anything with it. That really stifles innovation. I am excited about it, and I think that regulatory areas where there is some freedom will advance in fields and leave the rest of the world behind. We shouldn’t allow that to happen. We should have every country working on these technologies diligently and perfecting them. The problem with technology isn’t people having it, because they’re going to get it no matter what. We should be getting lots of groups doing this, not just one. It’s ineffective or damaging technology that hurts people, not its existence. 

So it’s best to acknowledge its existence and make sure it’s functional and safe rather than pretending it doesn’t exist, which can force people to go underground? 

Right. So now that it exists do we expect a group of scientists in a couple of places to do it right? No. We should do be doing it here and everywhere. We should be making sure every country is doing diligent work and sharing those results with one another. 

What is your background and what got you interested in aging? 

I had been helping groups with some stem cell web pages and non-profit work, because I thought it was incredible technology. Then came my big run for genetics. You know everything that I’ve come across tells me this is where the cures will come from. I wanted to help the kids I met and I remember being upset hearing some diseases being classed as manageable. I was searching for different things I could do. I looked at stem cells for regenerative medicine – illnesses, organs and people’s right to try. Then I ran into the SENS foundation and they were having a conference related to genetics. Before I wasn’t too sure about longevity research, but as I was sitting there I realised that we could really fight an old man’s war. A war where older people could stand at the frontlines. 

This may be an expansion on what we’ve already talked about, but what do you feel are the major roadblocks ahead? 

There will be roadblocks and I predict we’re going to have a big human rights issue. Certainly more and more people are going to want to come up and save their existence, right? It’s your life. We can’t afford the costs of Alzheimer’s, heart disease and cancer, so attacking biological aging makes sense. But at this time biological aging isn’t considered a disease! Even if conventional methods more successful, more successful than they have been thus far, if we could tackle some of the symptoms of Alzheimer’s, cancer, heart disease…you’ll just get another disease because you’re still aging. The roadblocks are going to be human accessibility. They’re going to come in as companies like ours move forward to do this in a safe way with a medical doctor. The FDA or regulatory industries are not going to be happy about us, they don’t really want people doing this at home right? So how do you create a safe zone for people to try things and be looked after by medical professionals, when you’re treating something that isn’t considered a disease yet. The hurdles are big. They’re both financial and human rights related – actually saving people. 

What made you decide to do this now?

The reason we’re doing what we’re doing now is because if we went another route, like the FDA, we’d have to pick a disease and then wait decades to get a therapeutic through it. Then you could only get it if you had that disease, which would leave everyone else in the market out. That doesn’t make sense. They would it’s going to take 15-20 years to get a drug through, but 100,000 people are going to die today! We’re so detached, how do you say that without feeling emotional? That’s it, their value to this earth is gone. And it’s real to them, it’s very real to them. To us it seems like fantasy, but to them they’re facing their last moment, and we shouldn’t feel comfortable with that. Feeling comfortable with that ensures that that will be us when our times comes up. I couldn’t understand why we were sitting on this research and not moving it forward immediately. 

We need to get people to sit up and realise this will be me someday, or someone I love?

I think that’s true. People just think there’ll be a cure in the future, which leads to complacency. They would say diseases like Parkinson’s are just something grandparents get. They don’t realise because they spend so much time avoiding the thought and living in the moment that their life is moving towards that same end. Many people believe nothing can be done about such things and simply ignore it. This is a major part of the problem. This is why raising awareness is paramount and advocacy is a major part of building that understanding in others. 

So even if people think you’re crazy, and things don’t go to plan, what’s the worst that can happen?

That’s the thing that really amazes me about the world. People will say ‘wow, why would you take a risk like that?’, and yet they drive a car everyday. Life is dangerous!. Look at what your life has to offer; the fruits of your life. I’m not saying it can’t be wonderful after 50, but I don’t see value in being a coward crossing my fingers thinking maybe I’ll be one of the lucky ones; I shouldn’t support gene therapy because I’ll be somewhat healthy until 70. I would be so disappointed on my deathbed thinking I probably should have done that, as it just might have helped advance something. 

The FDA is being pressured to consider aging a disease with a metformin trial. If we manage to convince them do you think it would massively boost prospects? 

Absolutely. It would open up avenues for research and interventions previously closed to scientists working in the U.S. and maybe capture the public support the field deserves. The International Longevity Alliance and the American Longevity Alliance are working towards a big push to get aging classified as a disease. It would help to get government money into research and create scenarios where people can actually study aging as a disease. It will go mainstream. We need more brilliant mind power behind this. What would be great is if proposals such as the Metformin trial can gain FDA approval and health and longevity benefits can be demonstrated. This would help increase support and interest within the wider population and open the door to mainstream acceptance of longevity research. 

So solutions like drug repurposement are a good bridge until we have more potent therapies like gene therapy?

Proposals like the Metformin longevity trial are an important starting point towards exploration of more robust longevity therapies and wider acceptance. It is my hope we will be successful with gene therapy and I believe we stand to learn a great deal from the data being collected. In the near future those at high risk of conditions such as Alzheimer’s will be the pioneers of these kinds of therapies and pave the way to more general application of the technology.

                                            A viral vector delivering a gene. Credit: Genome Research Limited

                                            A viral vector delivering a gene. Credit: Genome Research Limited

 How do you think we can boost gene therapy’s appeal? Where does this fear come from? 

We have to spread the word! We need to show people how advanced it is. When I talk to people about it, many people are interested in gene therapy because it doesn’t come with many of the problems associated with pharmaceuticals. I think people will really get on board with gene therapy as long as they have access to the information; this includes access to the studies demonstrating  age reversal and rejuvenation in animals. The FG21 mouse (2) lived significantly longer and remained healthy. Studies like this demonstrate the potential of gene therapy. Perhaps we will see similar positive results from my therapy because I want to be out there as a spokesperson for it. I think the key to building awareness of the work and its potential is advocacy, we need to get out there and engage with people and show them what is possible. Longevity science will only progress with wide public support and advocacy. This is something anyone can help do. 

I think that people need to actually see some of the clinical trials being done; there are children with muscular dystrophy right now being treated with gene therapy (3). Do we think of them as being wrong or different or scary? No, we don’t. If people could see what’s going on in the clinic, there are so many gene therapies running right now with hundreds of people involved. I don’t think anyone would judge them, and if they see great results then people would be more excited. It’s just like anything else that starts small, but can be turned into a really big movement and get people more interested in their health. If people saw the myostatin inhibitor and thought ‘well that might actually help me lose some of this white fat and get in shape. I can get out there and do more things’, they would get more involved. In the same way that immunizations have been incredibly powerful and changed the paradigm of how we used to die, I believe gene therapy will change the way we view health, aging, and disease.

Interested? Find out more at BioViva’s site

  1.  Spilsbury, Alison et al. “The role of telomerase protein TERT in Alzheimer’s Disease and in Tau-related pathology in vitro.” The Journal of Neuroscience 35.4 (2015): 1659-1674.

  2.  Zhang, Yuan et al. “The starvation hormone, fibroblast growth factor-21, extends lifespan in mice.” Elife 1 (2012): e00065.

  3. Mendell, Jerry R et al. “A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy.” Molecular Therapy 23.1 (2015): 192-201.

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