Did a biotech CEO successfully reverse her own aging process? Maybe not.

Elizabeth Parrish, CEO of BioViva.
Humans have been searching for the fountain of youth for millenia, dating back to ancient times. No one has found it yet, so I was very skeptical when I saw the recent announcement from BioViva, a biotech company, of what they called the first successful gene therapy against human aging:
"Elizabeth Parrish, CEO of Bioviva USA Inc., has become the first human being to be successfully rejuvenated by gene therapy, after her own company's experimental therapies reversed 20 years of normal telomere shortening."
That's quite a dramatic claim. If true, this would be a historic breakthrough: no one has ever reversed aging before. While human life expectancy has doubled over the past 150 years, virtually all of this progress has been from preventing early deaths, thanks to the developments of antibiotics, vaccines, and public health advances such as clean water.
Human life expectancy has doubled since the 1840's.
Figure source: Natl Institute on Aging.
Most claims about anti-aging therapies are easily dismissed as pseudoscience, nonsense, or scams. Not this one, though. BioViva has two experimental therapies, both based on legitimate science, and both with at least a chance of working. Neither has yet been proven to work in humans, but both are plausible.

According to BioViva and to interviews with its CEO, Elizabeth Parrish, Parrish received two therapies last year, one to protect against the loss of muscle mass, and one to lengthen her telomeres. The recent announcement claims that the telomere-lengthening therapy is already working, so I looked a bit deeper to understand what might be going on.

First a bit of background: telomeres are special DNA sequences that act as "caps" on both ends of every chromosome, providing a kind of protection for your genes. Each time a cell divides, its telomeres get a little bit shorter, and eventually they get too short and the cell dies. Telomeres therefore act as a kind of molecular clock that tells a cell how old it is. Our cells also have a special enzyme called telomerase that rebuilds telomeres. Cells with lots of telomerase can live much longer, and those without it die more quickly. Discovering how this all worked was a tremendous scientific achievement, for which Elizabeth Blackburn, Carol Greider, and Jack Szostak received the 2009 Nobel Prize.

Scientists have been speculating for years that telomerase might somehow hold the key to aging. BioViva's gene therapy delivers telomerase to the blood with the help of weakened viruses called adeno-associated viruses (AAVs), which they modified to carry the telomerase gene. The virus infects human cells and releases its payload into them, where the "transgene" produces extra telomerase.

This may sound very nice, but it's really, really complicated in practice. Gene therapy can have unexpected negative effects, and no human trials have yet shown that anyone can deliver telomerase effectively to human cells. However, studies in mice have shown some remarkable results: in 2012, a group of scientists at the Spanish National Cancer Centre used AAV to deliver telomerase to mice, and found that it "had remarkable beneficial effects on health and fitness" and that
"telomerase-treated mice, both at 1-year and 2-years of age, had an increase in median lifespan of 24 and 13%, respectively."
This exciting scientific result, and a few others like it, are what led BioViva and Elizabeth Parrish to try the same therapy in humans.

But did it work? Well, this is where things get a bit fuzzy. BioViva claims it did, based on their measurements of the length of telomeres in Parrish's white blood cells in September 2015, before therapy started, and again in March 2016. They claim that her telomeres got longer, from 6.71 kilobases (a kilobase is 1000 DNA letters) to 7.33 kilobases. This increase corresponds to about 20 years of aging: in other words, Parrish's white blood cells "have become biologically younger," as the company reported.

Setting aside the problem that we cannot really conclude anything from an experiment involving only one person, we can still ask: did Parrish's telomeres really get longer? As much as I want to believe BioViva's claim, there are several rather serious problems here. First, the company itself reported that Parrish's telomeres were unusually short for her age before the experiment began. Does this mean that the measurements were simply a bit off, and the second measurements were closer to the true number? Second, as UCLA's Prof. Rita Effros explained in an interview at geneticexperts.org,
"The overarching problem is that peripheral blood contains a mixture of many different cell types with disparate telomere lengths.... Thus, a simple change in the proportion of different cell types within the peripheral blood could easily explain the data."
In other words, it's possible that Parrish's telomeres did not get any longer. Despite the apparently precise numbers, BioViva has not provided any details showing that these measurements are accurate and reproducible (and they didn't respond to my request for these details). Their claim might be much more convincing if they made multiple measurements, both before and after treatment, and if these measurements showed that Parrish's telomere lengths really did increase.

There are a number of red flags about BioViva itself. Parrish herself is not a scientist, though she is an eloquent spokesperson for her company's therapies. More concerning is their Chief Medical Officer, Jason Williams, who previously ran "a dubious stem cell clinic," Precision StemCell (now located in Mexico) that offers stem cell therapies to patients with ALS (Lou Gehrig's disease), for which there is no evidence that they work. Personally, I would not trust Dr. Williams with my medical care.

The bottom line is that we simply don't know if BioViva's treatment worked on Elizabeth Parrish. They need to produce more data, on more patients, to construct even a mildly convincing scientific argument. Getting more patients may be very difficult, though: Parrish bypassed FDA regulations by traveling outside the U.S. (to Colombia) to conduct this experiment on herself.

Telomerase treatment to reverse aging is very promising, and it might really work, someday. I sincerely hope it will.  For now, though, BioViva's announcement leaves me very skeptical.

2 comments:

  1. What I don't get is why George Church hasn't distanced himself from BioViva and is still on their advisory board (at least according to their website).

    ReplyDelete
    Replies
    1. I had the same question. Church has made some statements about it but he is still on the board. Apparently he's on dozens - if not hundreds - of advisory boards, so he can't possibly pay attention to most of them.

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