Can this woman cure ageing with gene therapy?

Biotech boss Elizabeth Parrish has tried out her companys anti-ageing gene therapy with, she says, amazing results. Too good to be true?

Elizabeth Parrish is CEO of BioViva, a Seattle-based biotech company working to develop treatments to slow the ageing process. In April, the company revealed that Parrish herself had undergone the first gene therapy successful against human ageing. The treatment, it claimed, had reversed the biological age of her immune cells by 20 years.

There are a lot of fantastic conclusions that [people] can jump to, says Parrish defeating death, or people becoming immortal, or things like that. What were trying to do is hit the biggest point of suffering right now in the industrialised world, which is the diseases of ageing.

In September 2015, Parrish, then 44, flew to Colombia to receive two experimental gene therapies. One was a myostatin inhibitor, a drug that is being tested as a treatment for muscle loss. The other was a telomerase gene therapy the drug that BioViva claims has reversed her cells biological age, by lengthening parts of her genetic material called telomeres.

Genes are held in twisted molecules of DNA called chromosomes. At the ends of these chromosomes are stretches of DNA called telomeres. Telomeres protect the important genetic material from damage that can lead to disease-causing malfunction or cell death. Telomeres also allow the cell and its DNA to divide, but as cells divide a portion of the telomeres is lost until, after a finite number of divisions, the cell dies, a process that might contribute to the human ageingprocess.

If a cat has nine lives, then a dividinghuman cell has about 50 to 70 unless, the thinking goes, you lengthen the telomeres to extend the cells lifespan and increase its ability to withstand damage. The gene therapy that Parrish received is designed to do justthat by encouraging the cell to produce telomerase, a protein that repairs telomeres.

The treatment is highly controversial. Because BioViva had not done the necessary pre-clinical work to progress to human studies, the US Food and Drug Administration did not authorise Parrishs experiment hence her trip to an unnamed clinic in Colombia.

BioViva claims that six months after treatment the telomeres in Parrishs white blood cells had lengthened by 9%. It was an announcement met by a mixture of derision and incredulity by many scientists, who cited the lack of proper scientific procedure. We used third-party testing for everything, asserts Parrish. We used a standard telomere testing system that doctors sell and patients can buy over the internet. By that test, it said my telomeres in my [white blood cells] extended by the equivalent of 20years.

The scientists scepticism goes further than the reliability of the companys testing systems. On its website, BioViva claims that its work builds on that of Mara Blasco, director of the Spanish National Cancer Research Centre. In a2012 study, Blascos findings suggested that a similar telomerase gene therapy could increase the median lifespan of mice by around 20%. Her work since has focused on assessing whether the technology can improve outcomes in mice with heart and blood diseases that originate in very short telomeres.

Blasco does not associate herself with BioVivas work and she has no relation with the company or with Parrish. Clinical validation of our telomerase gene therapy strategy, as with any other therapies, should be achieved through rigorous trials validated and backed by the regulatory agencies, she says.

On her company profile Parrish describes herself as a humanitarian, entrepreneur and innovator and a leading voice for genetic cures. Absent from that list is the word scientist. She also describes herself as patient zero for these treatments a term some would take issue with. Patient zero is a typically used to describe the first patient in an infectious disease outbreak, rather than the first patient to have received a treatment. A better description, some would argue, is that hers was an n=1 study (a study on only one person).

Perhaps she is patient zero, but only for the spread of the pseudoscience thats going to grow from her story, says Timothy Caulfield, a professor in the Faculty of Law and the School of Public Health at the University of Alberta. Caulfield is concerned that Parrishs work lacks scientific rigour and is at risk of being picked up by unscrupulous practitioners aware of the selling power of anti-ageing treatments. People forget that most clinical trials dont pan out, he says. Drugs often look really promising in mice but dont pan out in people theyre different animals.

But Parrish, who says she has already had people contact her to ask if they can try her anti-ageing gene therapy, argues that enough animal studies have been conducted to move to humans. I think we are doing things wrong. We should be able to say, This looks promising, it didnt kill mice, it doesnt kill human cells. So what we said [when deciding to test her companys treatments] was, Lets just run a test; lets see if this stuff is safe.

Parrish and her team say they plan to explore the effects of the gene therapy in other cells in her body, and to assess the effect of the muscle-loss treatment. Meanwhile, they are looking to test the treatments in more people, but first they need to find a country with less stringent requirements than the US. We are still looking for a faster route, says Parrish. We have gone from country to country, with groups who are asking these countries to re-regulate. They will come in with new regulatory standards with a fast track to get the most life-saving therapeutics to humans as fast aspossible.

While Caulfield admits that the drug development process is strict, he argues that it needs to be to maintain scientific rigour. Sure, were all looking at ways to get effective drugs to clinics quicker but this idea of foreign shopping until you can find the regulatory framework that is most friendly to your idea about how science should be done is a terrible mistake, he says. Good science should be universal.

Quick to distance himself from BioViva was George M Martin, professor of pathology at the University of Washington. Martin had agreed to be an adviser to the company after being visited at his university by Parrish but relinquished that role on hearing the news of Parrishs self-experiment. I resigned only weeks after accepting the invitation, I never attended a board meeting and I certainly had no inkling of her plans to carry out human interventions without any pre-clinical work, he says.

George Church, professor of genetics at Harvard Medical School and another of the BioVivas advisers, is wary of the idea that he has ties with the company. I wouldnt call them ties, he says. I advise people who need advice and they clearly need advice. Church says he advised the company to go through proper regulatory channels and to do the required pre-clinical work. If you just let people run loose without any advice, especially if they dont have training in medical research, then youre inviting consequences.

Its a point, he notes, that was tragically highlighted by a gene therapy trial in France that is believed to have caused cancer in two participants in 2003, and the 1999 death of Jesse Gelsinger, the first person to die in a clinical trial for the therapy. Both failures, he says, set back the whole field. Since then, the field has improved tremendously and is much safer but new drugs have to be tested in placebo controlled trials with animal testing first.

And its not just scientists who are cautious about how advanced therapeutics such as gene therapies or those that use stem cells are handled. The public and policymakers, whose attitudes can either help or hinder potential medical advances, are also twitchy about science that tinkers with the inner workings of life. If the debate around the powerful new genome-editing tool, Crispr/Cas9, is anything to go by, Parrishs approach to combating ageing wont roll out without significant scrutiny.

Duncan Baird is a professor of Cancer and Genetics at Cardiff Universitys School of Medicine. He urges caution over Parrishs impatient approach to unearthing treatments. Life and ageing are too biologically complicated to start boiling it all down to these entities at the ends of chromosomes [telomeres], he says. To pick out one particular phenomenon of telomere length as a key determinant of ageing and say that if youre going to lengthen telomeres youre magically going to cure ageing, Ithink thats fanciful.

Without a much greater understanding of the biological processes that underlie ageing, such tampering can be dangerous, says Baird. One of the reasons telomeres have evolved to be the length they are, he says, is to limit the number of times a cell can proliferate and thus to limit its potential to be cancerous. Meddling with a fundamentally important tumour-suppressive mechanism that has evolved in long-lived species like ours doesnt strike me as a particularly good idea.

Attempts to combat ageing, and its myriad manifestations, do not belong to Parrish alone. Around the world, teams of dedicated researchers are doing the painstakingly thorough work needed to unpick the biological mysteries of ageing and, maybe one day, figure out how to tackle it. But, as so often with science, it seems success might lie in the very thing that Parrish refuses to accept: time itself.

Read more: https://www.theguardian.com/science/2016/jul/24/elizabeth-parrish-gene-therapy-ageing