Buyer beware of this $1 million gene therapy for aging – MIT Technology Review

Its said that nothing is certain except death and taxes. But doubt has been cast over the former since the 1970s, when scientists picked at the seams of one of the fundamental mysteries of biology: the molecular reasons we get old and die.

The loose thread they pulled had to do with telomeresmolecular timepieces on the ends of chromosomes that shorten each time a cell divides, in effect giving it a fixed life span. Some tissues (such as the gut lining) renew almost constantly, and it was found that these have high levels of an enzyme called telomerase, which works to rebuild and extend the telomeres so cells can keep dividing.

That was enough to win Elizabeth Blackburn, Carol Greider, and Jack Szostak a Nobel Prize in 2009. The obvious question, then, was whether telomerase could protect any cell from agingand maybe extend the life of entire organisms, too.

While telomere-extending treatments in mice have yielded intriguing results, nobody has demonstrated that tweaking the molecular clocks has benefits for humans. That isnt stopping one US startup from advertising a telomere-boosting genetic therapyat a price.

Libella Gene Therapeutics, based in Manhattan, Kansas, claims it is now offering a gene therapy to repair telomeres at a clinic in Colombia for $1 million a dose. The company announced on November 21 that it was recruiting patients into what it termed a pay-to-play clinical trial.

Buyer beware, though: this trial is for an unproven, untested treatment that might even be harmful to your health.

The company proposes to inject patients with viruses carrying the genetic instructions cells need to manufacture telomerase reverse transcriptase, a molecule involved in extending the length of telomeres.

The dangers are enormous, says Jerry Shay, a world expert on aging and cancer at the University of Texas Southwestern Medical Center. Theres a risk of activating a pre-cancerous cell thats got all the alterations except telomerase, especially in people 65 and over.

For years now, people involved in the company have made shifting claims about the study, raising uncertainty about who is involved, when it might start, and even where it would occur. Trial listings posted in October to clinicaltrials.gov currently show plans for three linked experiments, each with five patients, targeting critical limb ischemia, Alzheimers, and aging, respectively.

Jeff Mathis, president of Libella, told MIT Technology Review that two patients have already paid the enormous fee to take part in the study: a 90-year-old-woman and a 79-year-old man, both US citizens. He said they could receive the gene therapy by the second week of January 2020.

The decision to charge patients a fortune to participate in the study of an experimental treatment is a red flag, say ethics experts. Whats the moral justification for charging individuals with Alzheimers? asks Leigh Turner, at the University of Minnesotas Center for Bioethics. Why charge those bearing all the risk?

The telomere study is occurring outside the US because it has not been approved by the Food and Drug Administration. Details posted to clincaltrials.gov indicate that the injections would be carried out at the IPS Arcasalud SAS medical clinic in Zipaquir, Colombia, 40 kilometers (25 miles) north of Bogot.

It takes a lot longer, is a lot more expensive, to get anything done in the US in a timely fashion, Mathis says of Libellas choice to go offshore.

To some promoters of telomerase gene therapy, urgency is justified. Heres the ethical dilemma: Do you run fast and run the risk of low credibility, or move slowly and have more credibility and global acceptancebut meanwhile people have died? says Mike Fossel, the president of Telocyte, a company planning to run a study of telomerase gene therapy for Alzhheimer's in the US if it can win FDA signoff.

Our reporting revealed a number of unanswered questions about the trial. According to the listings, the principal investigatorwhich is to say the doctor in charge--is Jorge Ulloa, a vascular surgeon rather than an expert in gene transfer. I dont see someone with relevant scientific expertise, says Turner.

Furthermore, Bill Andrews, who is listed as Libellas chief scientific officer, says he does not know who Ulloa is, even though on Libellas website, the mens photos appear together on the list of team members. He said he believed that different doctors were leading the trial.

Turner also expressed concerns about the proposed 10-day observation period described in the posting for the overseas study: If someone pays, shows up, has treatment, and doesnt stick around very long, how are follow-up questions taking place? Where are they taking place?

Companies seeking to try the telomere approach often point to the work of Maria Blasco, a Spanish scientist who reported that telomere-lengthening gene therapy benefited mice and did not cause cancer. Blasco, director of the Spanish National Centre for Cancer Research, says she believes many more studies should be done before trying such a gene experiment on a person.

This isnt the first time Libella has announced that its trial would begin imminently. It claimed in late 2017 that human trials of the telomerase therapy would begin in the next few weeks. In 2016, Andrews (then partnered with biotech startup BioViva) claimed that construction of an age reversal clinic on the island nation of Fiji would be complete before the end of the year. Neither came to pass.

Similar questions surround Libellas most recent claims that it has two paying clients. Pedro Fabian Davalos Berdugo, manager of Arcasalud, said three patients were awaiting treatment in December. But Bioaccess, a Colombian contract research organization facilitating the Libella trial, said that no patients had yet been enrolled.

Also unclear is where Libella is obtaining the viruses needed for the treatment. Virovek, a California biotech company identified by several sources as Libellas manufacturer, did not answer questions about whether any treatment had been produced.