BioViva Moving Ahead With Human Gene Therapy for Telomerase Activation

BioViva is one of the small groups interested in bringing telomerase therapies to humans sooner rather than later. It seems they have started in on their small long-term trial of human gene therapy for telomerase activation, and have treated the first volunteer.

I should say that at any given time there is a fairly large gap between what can be done in human medicine, the technology that actually exists and works, and what is being done in trials. Most of this gap is due to regulation, and the rest of it because development groups want to have a reasonable certainty that what they are doing actually works, does more good than harm, and so forth. The regulatory process might last a decade, while the actually useful part of that testing (does it basically work, and is the risk profile sufficiently defined and acceptable to patients) is only a few years. As the cost of research and development in the life sciences falls, it will become increasingly untenable that a huge ball and chain slows progress thanks to regulatory risk aversion, and a growing number of initiatives will forge ahead and build anyway. Some years ago I proposed the Vegas Group fable, something that I think will happen in the fullness of time: alternative roads that bypass official regulation in favor of faster progress, an inevitability in an environment of low-cost research. Also, I think, a necessity.

What about the science here? I've never been a big fan of telomere lengthening approaches, as average telomere length as it is measured today in immune cells looks very much like a marker of the progress of aging, an end stage consequence far removed from root causes. Telomeres shorten with cell division and new long-telomere cells are delivered into tissues by stem cell populations. Thus average telomere length in immune cells reflects some combination of immune health and stem cell activity, both of which are known to decline with age. You can't argue with the fact that telomerase gene therapy has been shown to extend life in mice, however, though you can certainly note that the size of the effect has been getting smaller as the research groups have refined their data and approaches.

How does this work to slow aging in mice? At this point I lump enhanced telomerase activity into the general category of approaches that either probably work or intend to work by boosting the activation of old stem cell populations, resulting in increased repair and tissue maintenance and thus a slower decline into frailty and organ failure. More telomerase doesn't seem to raise cancer risk in mice, but mice have very different telomere dynamics and cancer risk profiles than we humans. The fastest way to figure out what is going to happen in humans is of course to try it, and kudos to anyone volunteering at this stage, but I'd be waiting for a few more years of testing first in animal or tissue models closer to human telomere dynamics. In part that decision would be driven by the fact that I don't think that this is the best approach to move ahead with practical applications, to push ahead and get things done. I absolutely agree that pushing ahead to get things done needs to happen, but I'd rather see this sort of boldness for SENS treatments like senescent cell clearance.

BioViva USA, Inc. has become the first company to treat a person with gene therapy to reverse biological aging, using a combination of two therapies developed and applied outside the United States of America. Testing and research on these therapies is continuing in BioViva's affiliated labs worldwide. BioViva CEO Elizabeth Parrish announced that the subject is doing well and has resumed regular activities. Preliminary results will be evaluated at 5 and 8 months with full outcome expected at 12 months. The patient will then be monitored every year for 8 years.

Gene therapy allows doctors to treat disease at the cellular level by inserting a gene into a patient's cells instead of using the regular modalities of oral drugs or surgery. BioViva is testing several approaches to age reversal, including using gene therapy to introduce genes into the body. Although not generally considered a disease, cellular aging is the leading cause of death in the developed world. Side effects like muscle wasting (sarcopenia), grey hair and memory loss are the well-known hallmarks. And the aging cell is also responsible for the diseases of aging, including Alzheimer's disease, heart disease and cancer. BioViva is leading the charge to treat the aging cell and reverse aging. "The aging cell is a key factor that has been overlooked for too long. Companies have put millions of dollars into treating the diseases of aging, such as dementia, frailty, kidney failure and Parkinson's disease, and we still do not have a cure. Aging involves multiple pathways. We wanted to target more than one for a better outcome."



You forgot to mention the other treatment they applied, the myostatin inhibitor AAV gene therapy

Posted by: Nicolai at October 2nd, 2015 6:16 AM

@Nicolai: It wasn't clear from the release that they'd moved ahead with more than telomerase enhancement. Myostatin therapies I'm more bullish on, though there are people more familiar with the research than I who think that the case hasn't yet been made for a clearly effective treatment along those lines lacking potentially very serious side-effects. E.g.:

There are a lot of posts on myostatin research in mice and potential benefits from treatment, largely revolving around increased muscle mass, back in the archives:

Posted by: Reason at October 2nd, 2015 6:26 AM

I sure as **** hope they don't end up killing some people and repeating the gene-edit-adenovirus debacle of 1999.

Posted by: Arren Brandt at October 2nd, 2015 7:14 AM

I hope you're right Arren. But I commend them for doing something in humans. They've been saying it's time to try it, and they did.

Posted by: Ham at October 2nd, 2015 7:22 AM

Speaking of moving ahead in medical research, has anyone heard what happened to Ido Bachelet work on DNA nanobots. He was suppose to work on a patient who was suppose to have only a few months to live w/o the procedure that Ido proposes. This was earlier this year and there has been no news of it.

Posted by: Robert Church at October 2nd, 2015 10:54 AM

@ Robert

Yeah Ido Bachelet has been really quiet since this was supposed to happen. The only thing I've heard of was him having meetings with Pfizer about this. There's only been speculation about what's happened, or if anything even happened. People ask about this on reddit every week or so and no one has any idea still :(

Posted by: Ham at October 2nd, 2015 11:41 AM

To clarify the two therapies in question are htert and a proprietary myostatin inhibitor that has in animal data and anecdotal human data shown to reduce atherosclerosis. The hope is the combination has synergy to rejuvenate stem cells and combat Atherosclerosis as well as muscle wastage.

Posted by: Steve h at October 2nd, 2015 1:47 PM

Robert, the human trial was announced in October 2014. Then, a partnership with Pfizer was announced in May 2015. This latter event may have to do with Bachelet staying mum on the matter.

Posted by: Nico at October 2nd, 2015 1:57 PM

Well according to the SENS model of aging, boosting telomerase is not dealing with the damage that is aging (except maybe helping a little with cell loss, but that is debatable).

Myostatin in more interesting. Surely bodybuilders around the world must be interested in giving it a try.

Posted by: Jim at October 2nd, 2015 4:49 PM

Telomere attrition comes mainly from oxidative stress and division. It would be hard to treat oxidative damage as it occurs naturally when you breathe.

Telomerase has a number of functions beside simply maintaining telomere length. It interacts with the wnt pathway to facilitate regeneration and repair and growth. It is instrumental in stem cell mobilization and as various stem cells suffer telomere attrition (not all can maintain telomeres) falling availability of telomerase means stem cell dysfunction is inevitable. And another key factor is telomere length and gene expression, as they shorten a significant number of genes change for the worse and the cell becomes functionally old.

Some people dismiss telomere length as an indicator of cellular stress but they are far more complicated than that. Lengthening Telomeres have also clearly demonstrated to change gene expression profile in human as well as animal cell lines and shifted function to more youthful levels.

Telomeres are not the cause of aging but they are a suitable intervention point. If you are interested in telomere biology I suggest Dr fossels book cells, ageing and human disease as a very good academic book.

I applaud bioviva for taking a different approach though you will notice on their website a number of their cellular targets match those of sens.

Posted by: Steve h at October 3rd, 2015 7:42 AM

Oh and short Telomeres also effect mitochondria via the p53 pcg1 pathway as well as stem cell mobility and metabolism via the same pathway.

I believe regeneration of resident stem cells coupled with implants of fresh stem cells in artificial niche to be a valid approach to this problem.

Mobilization of resident stem cells also addresses cell depletion so a certain level due to restoration of replicative potential

However bioviva freely admit it may or may not work as hoped with this particular vector. Only the data will tell us that and that's a waiting game. I know they are measuring various biomarkers including tat and qtrap telomere assays plus dnam assays and so on. Changes to functional cell age will be very obvious.

Posted by: Steve h at October 3rd, 2015 7:52 AM

Is there anything known about the patient? Even his age? If he were a senior it would theoretically be easier to see if there was a meaningful effect, right? Though it could also take decades to see if there is any real life extending benefits, I suppose.

Posted by: Ham at October 3rd, 2015 8:16 AM

Patient late forties early fifties. It's qu
easy to test various ageing biomarkers without waiting decades, they will use things like TAT and QTRAP to gauge telomere changes and track gene expression changes using illumina data run through the Horvath dnam and histone system to give an accurate cellular age. If the cellular age is baseline of a late forties male and subsequent samples return a younger expression pattern we know that the functional age of the cell has changed.very similar to how geron did it in the 90s only using diagnostics considerably more accurate and sophisticated.

Posted by: Steve h at October 3rd, 2015 1:59 PM

Does a part of anyone wonder if this could be more on the side of a scam to market towards desperate people? I'm not suggesting it is, just curious, as that's the idea being tossed around on reddit ATM. Liz does seem like she's really sincere in wanting to help people. The poor bioviva website is a target of criticism along with some of the links on it. I understand the reasons for not having a top notch site yet though. Someone also pointed out that this hasn't been all over the news yet. Why? You would think it would be talked about a bit more.

I'm glad this is moving forward, because we won't know until we try, but I hope nothing bad happens to the patient. That could cause huge setbacks.

Posted by: Ham at October 3rd, 2015 2:04 PM

Interesting, thanks Steve.

Posted by: Ham at October 3rd, 2015 3:47 PM

Ham, I see that G. Church and Aubrey are allegedly on their advisory board. However fishy might Bioviva be, I hope it won't tarnish their careers.

Posted by: Nico at October 4th, 2015 5:34 PM

Just ask Aubrey or George if you think it's fishy.

Posted by: Steve h at October 6th, 2015 12:10 AM

Its NOT a scam if it has potential, regardless if its marketed to desperate people or not. I'd reserve the word scam for unmerited hype for a quick buck. Creating access to informed options where there was none can only be a good thing.

Posted by: Troy at October 6th, 2015 12:05 PM

Nope not a scam, it has definitely been tested, ask Aubrey he knows. Will it work? Not sure lets look at the data in a few months time.

Posted by: Steve H at October 6th, 2015 12:25 PM

Looking forward to seeing the data. Someone on reddit is working towards getting Liz Parrish to do an AMA soon. Hopefully that happens, it could be interesting.

Posted by: Ham at October 6th, 2015 3:08 PM

I applaud BioViva for fearlessly going around the FDA and conducting human trials outside of the USA. This makes a lot of sense as it reduces costs in both time and money. I would love to interview Liz Parrish or anyone involved in the project.

Posted by: troi+ at October 7th, 2015 5:26 PM


She's doing the AMA on reddit Sunday, October 11 starting at 11am pdt.

Posted by: Ham at October 7th, 2015 6:16 PM

Guys just an update Bioviva is doing an AMA about this on Reddit on 11th at 6 UTC

Posted by: Steve H at October 8th, 2015 2:49 AM

@ Troi check your email :)

Posted by: Steve H at October 8th, 2015 3:11 AM

Hi all,

Interesting read! Agree with Steve, as he mentioned, telomerase's mRNA catalytic subunit and its hTERT transcript are an incredible opportunity to create true biorejuvenation in the real sense if controled against deleterious cancer telomerase jacking mutations. The telomeric DNA repeats (TTAGGG) of the telomeres control the gene signature program age-phenotype. As mentioned, this gene pattern change by telomere size attrition activates the death genes program in low telomeric kb/bp (kilobytes/basepairs) gene space. Studies have shown that telomerase lenghtens stem cells' telomeres during stem cell reprogrammation/total rejuvenation (see induced adult pluripotent mesenchymal stem cell reprogramming) and they are ready to differentiate anew and rebuild organ tissues from scratch - the damage, which is an (epi)genetic signature is retroprogrammed to a no damage gene signature (their heightened telomeres back up to 16kb reverse age to 0). Some studies stipulate that the DNA does not change between aged or young body - only the epigene structure surrounding it and the chromosome does, creating this genetic aging and gene pattern of aging.

Damaged stem cells accumulate short, unstable, demethylated telomeres too. This impedes the transcription fidelity of the gene network, meaning certain critical transcripts (hTERT transcript for telomerase activity becomes unstable and inactivated (cancers use telomerase to their own advantage when telomeres become sufficiently short from excess inflammation oxidative stress accumulation and genetically highly unstable (at about 2kb telomeres length, the s... hits the fan). What's more is that the cell Redox (Glutathione:Oxidized Glutathione) changes and contributes directly to the possibility of telomerase elongation access to telomeres during the cell division cycle. Studies showed that the oxidative stress, under Redox regulation, is in direct correlation to the cell's redox state. It is very telling that humans living 100 years maintain low adequate blood glucose, low oxidative stress, low glycated hemoglobin and albumin, low pancreatic beta-cell insulin production, high red blood cell Redox, high glutathione reductase, high levels of quiescent stem cell pools, high overall protection, but especially high maintenance of telomerase activity and enough elongation to slow things down; the antioxidant systems can only do so much if telomerase is weak.

How so ? Telomerase is shunted away from the smallest critical telomeres when oxidative stress rises and that leaves whatever exhausted redox antioxidant systems left (catalase, SOD, heat shock proteins, heme oxygenase-1, metalothionein, uric acid, ascorbate, ubiquinols, coq9 10, etc) to try to mitigate the final damages to a certain end because gene silencing of bad death genes is abolished in short telomeres genespace (p53, p16, p38 and other tumor suppressors that are a paradox for destroying cancers but creating inflammation telomeres attrition in good cells, a evolution mechanism to control longevity and allow human lifespan with heavy tumor burden suppression). Plus studies have shown low Redox can reduce telomerase activity by upwards to 80%, rendering it near useless. They are interconnected pathways that depend as a whole on each other to telomeric gene signal rejuvenate and repair damages, telomerase, redox, blood glucose, telomeres length, insulin resistance, glycation, all, in unison, to oxidative stress and thus aging.

High telomerase is our gateway to immortality, no joke, telomerase and telomeres are a real epigenetic biorejuvenation, by way of the cell Redox, it's still only in infancy but surely one day as in mice that we will biorejuvenate repeatedly to live at least a full 100 years like a human and surpass it; then we will be very close to the holy grail ponce de lèon was after. Maybe not in our lifetime though, seeing it takes some 100 years and more to see truly big revolutionary changes. Let's hope.

Posted by: CANanonymity at October 8th, 2015 9:57 PM

@ CANanonymity impressive summary! I have to ask are you a researcher? And if not you should be :)

Posted by: Steve H at October 9th, 2015 5:55 AM

As a biology student this is very interesting. I have read that certain turtles and Kelly fish repair the telomeres after every cell production and that the same alle is found in the human genenode but has been switched off. Does this theropy switch on the expression or does the theropy offer new DNA introduced to produce the telomerase.

Posted by: Demetrius Mustain at June 2nd, 2016 1:33 PM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.