Claim of risky DIY gene therapy linked to unlicensed stem cell clinic

Elizabeth ParrishIn a strange, but fascinating tale recounted by Antonio Regalado in an article over at MIT Tech Review, we hear the first claim of a do-it-yourself (DIY) gene therapy.

The owner of a small biotech called BioViva, Elizabeth “Liz” Parrish, reportedly traveled from her home in Seattle to get an unapproved, experimental gene therapy in another country.

The article pointed to a Reddit AMA that Parrish recently did where she discussed these events in the context of her interest in anti-aging efforts.

Regalado is fairly blunt about his view of the anti-aging crowd, describing it this way:

“The field of anti-aging research is known for attracting a mix of serious scientists, vitamin entrepreneurs, futurists, and cranks peddling various paths to immortality, including brain freezing.”

In the introduction to the AMA, Parrish is described as, “”the woman who wants to genetically engineer you.” You can read more about her here on her LinkedIn profile.

Below is a video of Parrish discussing anti-aging therapy. She’s clearly very articulate and bright. In the talk she claims that the doctor that she works with at BioViva received an anti-heart disease gene therapy five years ago and is doing well. It’s an extraordinary claim.

She also talks about stem cells and cures for a variety of serious and even fatal diseases such as ALS.

Apparently Parrish’s DIY “therapy” involved two components.

One effort targeted muscle through introduction (presumably through injections of virus?) of the follastatin gene into her muscle. The rationale seems to be that it would inhibit myostatin and give her big muscles. The second intervention reportedly was an IV of “viruses that express telomerase”.

The second one sounds particularly risky given the association between elevated telomerase and cancer. Many things can go wrong with gene therapy and when you combine that with DIY administration it gets even scarier.

Who knows the possible consequences of either of these gene therapies? Even tightly-regulated, experimental gene therapies in the past given as parts of controlled clinical trials have led to deaths. I hope that doesn’t happen here, but if true this situation sounds radical and possibly dangerous.

Still BioViva has had some impressive scientists on board. One, George Martin of the UW, has terminated his link to the company after these recent events. Harvard geneticist George Church, a transhumanist and at times a proponent of human genetic modification, apparently remains on board with BioViva.

By getting an unapproved and potentially dangerous gene therapy abroad, Regalado reports that Parrish was intentionally circumventing the FDA:

“Parrish said in an interview she chose to bypass the U.S. Food and Drug Administration by trying the procedure overseas. The FDA requires costly trials, and aging itself is not generally recognized as a disease that can be addressed by drugs. “What we did is we moved forward to try to treat biological aging,” Parrish says. “We are attempting to reverse aging at a biological level.”

This sidestepping of the FDA was not viewed positively by Church, but he indicated he was inclined to believe that the gene therapy intervention was real. He also has at other times recently been enthusiastic about the concept of a telomerase intervention in people as an approach to aging:

“Church, the Harvard professor, says he thinks targeted DNA changes could in fact extend the normal human life span, which has a maximum length of about 120 years. Earlier this month, at a meeting of the National Academy of Sciences organized to weigh policy on genetic interventions, Church proposed telomerase as one bearing serious consideration. “I think we are very close. I think the world is close, so long as we don’t have a setback,” he says. “The extension of life span is quite dramatic in model organisms … it would be amazing in humans.”

Again, to me the cancer connection with telomerase makes this a dangerous shot in the dark.

This tale gets more puzzling as Regalado points out the involvement of Jason Williams, who is more well-known in the stem cell world for his dubious stem cell clinic (Precision StemCell) that had been located here in the US. He has since moved that abroad after a situation with the FDA. Apparently Williams is also the co-owner of BioViva and he indicated to Regalado that Parrish’s DIY gene therapy took place in Colombia, but not at his clinic.

Parrish seems to espouse a very libertarian view of biomedicine and bioethics:

“We as a company have our own ethics,” she says, referring to what she calls the need for inexpensive gene therapy treatments. “I am certainly not going to ask someone’s permission to potentially create new industries and cures.”

This sounds reminiscent of transhumanism and disruptive technological innovation, but sure seems extremely risky.

It also could set a dangerous precedent for DIY interventions or encourage others to follow this uncertain path. Is this a one-time thing or the start of a larger trend in the world of genetic interventions?

20 thoughts on “Claim of risky DIY gene therapy linked to unlicensed stem cell clinic

  1. It is the beginning of something new that will take on a life of its own and most likely result in the emergence of a parallel system of care.

    The convergence of several unique trends, including:

    – personalization of medicine on an “n-of-1” basis,
    – adaptive clinical design,
    – globalization of health care training,
    – compassionate use legislative initiatives for experimental therapies,
    – wider acceptance of complementary medical technologies,
    – the growth of international medical travel,
    – the fact that we spend $7 trillion annually and have an absence of curative interventions for any chronic degenerative diseases via traditionally regulated channels

    has brought this genie “out of the bottle”

    It is an interesting new era.

  2. Hi Paul,
    Let’s see if I have this right: The lack of telomerase is a risk factor for aging and too much telomerase is an enabler for cancer — and, perversely, aging is the biggest risk factor for cancer….

    I see that elephants have a whole lot more copies of the TP53 gene
    Perhaps those who fiddle telomerase would be well advised to add a few more copies of TP53?

    I wonder what new twist they’ll discover tomorrow?

    Ah, we are back to the old business of things being oh so multidimensional and nonlinear in their interactions. Being human is complicated enough. Being transhuman, that’s truly mind-blowing.

    On the other side of the argument, Big Government (like FDA and Health Canada) often seem so one-dimensional in their way of doing business:
    I don’t look to such agencies for illumination. Better to stick with the open literature.

  3. Follistatin gene therapy has at least been tested in Rhesus Monkeys, Telomerase has only been tested in rats (and then with extra tumor suppressor genes).

    The first treatment is highly risky, given the lack of human testing, but was almost at the point of a phase I safety trial. The second Telomerase treatment is fairly nuts in a lot of people’s views.

    Lets hope she doesn’t get cancer as this could be another Gelsinger moment for gene therapy.

  4. No.This isn’t snake oil.

    She took a chance with herself, with a research stage biologic, ex-U.S.

    The risk endured was technically no different than any Phase I tolerability study, with any new biologic entity, at the point of “first in human” experience.

    “Snake oil” is an expression that has come to refer to any product with questionable or unverifiable quality or benefit

    Pretty much anything can be labeled as such, including the endless array of products that FDA has oversight on today, that NEVER have to be tested in humans, that we consume on a daily basis as personal choices

    Also, if you look at most traditional drug development models, where big pharma endeavors to sell product X, to as many people with disease Y as possible, with full knowledge that based on 1) the inclusion / exclusion criteria of their registrational studies, and 2) the fact that even in 2015 we know next to nothing about the pharmacogenomic / toxicogenomic differences between individuals, that product X will only work in a % of patients with disease Y (and hopefully not cause an SAE or death in the rest that is fails to perform in), well… see where the real snake oil is being peddled.

  5. @Jim, I agree on your risk assessment. Other factors are how the viruses were produced and their quality, the doses (e.g. MOI) she received, and more. Scary stuff.

  6. @Ira,
    I get your points. I do have concerns over the comparison to a Phase I trial though. This is a very different situation. For instance, where were the viruses manufactured? A GMP facility in the US? What pre-clinical data support the experimental design, etc.?

    Also, what if other individuals are encouraged by this to follow suit? Will they pay?

  7. The “Phase 1/2a Follistatin Gene Therapy Trial for Becker Muscular Dystrophy” study done @ Nationwide Children’s Hospital, Columbus, Ohio,
    that is used as a reference

    seems like it had good results and they want to extend the studies:

    “The safety findings in combination with gene expression in
    muscle, and functional improvement provide a firm foundation
    for application of AAV1.FS344 gene delivery for other muscle diseases.
    We have initiated a trial in sporadic inclusion body myositis

    As for telomerase vs. cancer, Dr. Michael Fossel, Maria Blasco and couple
    other researchers, believe that actually increasing telomerase expression
    will re-consolidate telomeres that will lead to a more healthy/youthful

    There is a recent study that explains that cancer hijack the telomerase in order to become immortal.

    According to some researchers the opposite in not so true: increasing telomerase doesn’t lead to cancer.

    Of course these needs to be proved.

    he has a newly book just published about this subject

    “The Telomerase Revolution: The Enzyme That Holds the Key to Human Aging”

    he is banking this approach in Alzheimer’s with Telocyte Company:

    They work with Dr. Maria Blasco, C.N.I.O. from The Spanish National Research Centre

    they have lots of studies in Telomeres/Telomerase

    Telomeres and Telomerase Group

    There is also an interesting recent study done by Prof. Helen Blau @ Stanford:

    “Telomere extension turns back aging clock in cultured human cells, study finds”

  8. Ira – you say
    “Snake oil is an expression that has come to refer to any product with questionable or unverifiable quality or benefit”, which which I completely agree, and in your first post
    “The convergence of several unique trends, including personalization of medicine on an “n-of-1” basis…has brought this genie “out of the bottle”

    Surely n=1 would contribute to the unverifiable quality or benefit?

    Regarding telomerase, increasing activity should not directly contribute to cancerogenesis – it isn’t an oncogene. Telomerase prevents senescence and the lack of it drives selection of genetic mutations to overcome senescence. Hence, increasing telomerase may extend the lifetime of a pre-sencescent cell pool.

    What I wonder is whether it is beneficial to increase the lifespan of already aging cells – wouldn’t we generate zombie cells that are inefficient and should senesce but keep on burning resources?

  9. Stem cells given a top up to restore telomeres is a good thing as they can continue maintaining tissue. Telomere dysfunction has been shown by Ron Dephino to lead to stem cell decline via the P53-PCG1-Telomere path AKA the aging axis as he calls it.

    Somatic cells really should be allowed to die when needed but stem cells could prove useful when rejuvenated. We see the results of stem cell mobilization using the Conboys techniques which also restore telomeres but via factors not gene therapy.

    Not to suggest that this is not risky because it is but then so is waiting decades for the FDA to decide if we are allowed to treat aging as a disease, and that isn’t including the time after to research should they agree!

  10. The version of follistatin used in the Becker trial is a specific isoform; using a different isoform is not beneficial, if I recall correctly (may be buried in the rhesus paper).

    Regarding the telomerase part, the big problem I see is that it makes such a good story. On paper,it sounds so simple: telomerase extends your telomeres and makes you live longer! In reality, it’s more complicated, like most things in biology are. If we consider the Blau study, that’s cells in a dish. How exactly the mRNA (which is good: no integration) would actually be beneficial in vivo is a totally different situation. Keep in mind that you can grow tissue culture cells for longer by simply keeping them at physiologic (5% O2) rather than atmospheric (20%ish O2) oxygen levels. Now the telomerase gene therapy mouse trial from the Blasco lab…that study has issues. Ranging from inappropriate statistical tests to inexplicable results that contradict quite a few studies in the viral gene therapy field (the effects being majorly brain when the AAV serotype used doesn’t transduce neurons well), well, this is not something I would base a human therapy on.

    This whole bioviva thing smacks of Silicon Valley showmanship and what is the term, anarcho-capitalism (think Uber’s practices) to me. Who knows if she even actually got the treatment?

  11. I think I lost IQ points just from reading about this. Or at least a little sanity. NUTS. .. nuts nuts nuts. Meanwhile… treatments that have finished phase I studies done by scientists following all the rules are ignored and unknown almost completely. Ocata ‘ s amd treatment is the most obvious example… but not the only one.

  12. Problem I have with this as stated previously, here is what I posted on my Facebook response and is in line with Paul´s concerns “Well I am a little concerned with the use of hTERT! as the the single stranded rAAV DNA needs to be converted into a transcriptionally functional double-stranded template to be expressed at this point there may be potential for integration. Don´t get me wrong I am for people who are convinced with their science to test on themselves-no issues. But obviously if this is going to be a long term therapy I would like to have feedback with repeat dosing etc so there will be a need for careful immunosurveillance to be conducted as part of ongoing trial this will provide an understanding of the intricacies of the immune response in AAV-mediated gene transfer. I will be following this!”

    Another concern is Just say it does work this will lead to a major societal divide ie. the people who can afford this therapy and those who cannot…I am not an advocate of this…a clear divide is destined to form

  13. N=1 in-human trial is not a science, it’s just marketing.

    I can’t imagine anyone willingly doing this to themselves, especially when the evidence of efficacy in pre-clinical models not being especially clear-cut…

    My best guess? I bet she didn’t actually receive any treatment…. The whole thing smells like a scam.

    • “especially when the evidence of efficacy in pre-clinical models not being especially clear-cut”?

      Penicillin kills guinea pigs and produces birth defects in rats, aspirin is poisonous to cats, cancer has been “cured in mice” thousands of times, and dozens of drugs found safe in animals are later withdrawn from market due to adverse drug events in humans.

      Animal models remain poorly predictive for humans, yet remain a mandatory cornerstone behind years and millions of dollars of early drug development activities.

      An no, n-of-1 is not just marketing

  14. “n-of-1 is not just marketing”
    I agree – it is not even marketing – it is qualitative and hence not significant in clinical terms

  15. And therein lies the bifurcation that I spoke of at the beginning, that has evolved and will continue to grow into two defined camps in healthcare

    One, that more and more believes that the current system has failed them, and that the only important issue is how something works (or fails to work), in oneself

    And another, that is more comfortable with the status quo, and is comforted by how something works (or fails to work), in a sample of patients that may or may not represent the target population (and what happens in a range of non-human species)

    As I said at the beginning, it is a new era where we will see a lot of unique things occurring

  16. Hello Ira, there has always been a duality regarding medicine and medical practices – one following evidence based systems and the other not.

    Your comments about traditional pharma companies drive to profitability making a nonsense of this is in some cases sadly true (see Ben Goldacre’s book “Bad Pharma” – an excellent and slightly frightening read). But the basis of evidence- based medicine is the only way to ensure effective and safe therapies can be made available to the masses.

    Those that believe the system has failed them are probably those caught between no cure and a cure in development. This has been the case since the start of medicine and your n=1 used to be the homeopaths or bloodletters but now it’s those injecting themselves with gunk made from their own fat or genes that have no chance of effecting a result.

    What’s a real pity is that some of those being sold a dream / lie could be enrolling in trials to validate real therapies.

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