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The unproven gene therapy aims to lengthen a person’s telomeres
Would you pay $1 million and fly to South America for a chance to live longer?
Libella Gene Therapeutics, a Kansas-based company that says it is developing a gene therapy that can reverse aging by up to 20 years, is hoping your answer is yes. In an interview with OneZero, the company says it is ready to give an experimental anti-aging therapy to older people at a clinic north of Bogota, Colombia. But that’s not all — it’s also charging $1 million to participate. Scientists and ethicists say the company’s experiment is not only dubious but it also raises concerns about how anti-aging treatments should be tested in people.
The aim of Libella’s therapy is to lengthen a person’s telomeres, which sit at the tips of chromosomes like caps on the end of shoelaces. First discovered in the 1970s, telomeres have been linked to aging because they seem to shorten as a person gets older. By delivering a gene called TERT to cells, which in turn makes a telomere-rebuilding enzyme called telomerase, Libella thinks it can prevent, delay, or even reverse aging.
“I know what we’re trying to do sounds like science fiction, but I believe it’s a science reality,” Jeff Mathis, CEO of Libella Gene Therapeutics, tells OneZero.
Libella’s therapy is based on studies published by American geneticist Ronald DePinho in 2010 and Spanish scientist Maria Blasco in 2012, which found that telomerase gene therapy could reverse signs of aging in mice. While intriguing, many have dismissed the idea of using gene therapy to reverse aging in humans because it would involve a permanent change to a person’s DNA, a risk that’s hard to justify in someone who’s healthy.
Behind Libella’s technology is Bill Andrews, a molecular biologist who, 20 years ago, led a research group at the Bay Area biotech firm Geron to identify the human telomerase enzyme. He tells OneZero that he developed a telomerase gene therapy and licensed the technology to Libella. “I can’t say it’s the only cause of aging, but it plays a role in humans,” he says about telomere shortening.
The gene therapy he developed is similar to one that Elizabeth Parrish, CEO of Seattle-based longevity company BioViva, received at an unknown clinic in Colombia in 2015, says Andrews. Parrish is believed to be the first and only person so far to receive a gene therapy for anti-aging. In 2016, her company announced that the therapy successfully lengthened her telomeres, but the data has not been published in a peer-reviewed journal and it’s not known whether the therapy produced any health benefits. Mathis says he initially wanted to invest in BioViva but decided to start his own company instead.
According to a listing at ClinicalTrials.gov, which is maintained by the U.S. government, Libella is requiring participants to be 45 years of age or older. The company is initially enrolling five people in the study. It also plans to test the same gene therapy in five patients with Alzheimer’s disease and another five with critical limb ischemia, a condition in which a person’s arteries become severely obstructed, blocking blood flow to the limbs. Studies have shown only a weak link between telomere length and Alzheimer’s, and little research has been done on the association between telomeres and critical limb ischemia. Mathis says finding people to participate has not been easy, but the company has so far recruited two people willing to pay the steep fee. The first person, a 79-year-old, will receive the therapy in January for anti-aging.
“I think aging is one of the worst things that affects humans,” says Andrews. “If we had a cure for aging 200 years from now and we decided to have an election to see if we should ban it, I don’t think people would ever choose that and go back to the way things were.”
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The anti-aging field has drawn plenty of criticism for scams and overhyped products with no proven health benefits. Libella’s clinical trial listings also raise red flags. First among them is the fact that the company and its trials are located in different countries. Mathis, an occupational therapist who runs a rehabilitation practice in Manhattan, Kansas, says he chose Colombia for the trial because it was the “path of least resistance.” The company looked at eight different countries, and he says, “the easiest, the quickest, and the best way forward ended up being in Colombia.”
Leigh Turner, a bioethicist at the University of Minnesota who studies clinical trials that market unproven therapies, says he suspects the company chose to go outside the country to avoid the Food and Drug Administration, which oversees clinical trials in the United States. “Even though the company is based in the United States, they’ve managed to find a way to evade U.S. federal law by going to a jurisdiction where it’s easier to engage in this activity,” he tells OneZero.
Turner says the $1 million participation cost is alarming because most clinical trials are free. In fact, many pay people to participate because of the time commitment and the potential risks involved with receiving an experimental treatment. Andrews justifies the fee, saying it costs Libella “hundreds of thousands of dollars to produce enough of the gene therapy to treat one person.”
The Libella trials are not taking place at a major hospital or research institution but at a small clinic in Zipaquirá, Colombia, called IPS Arcasalud SAS. No other studies posted on ClinicalTrials.gov list the clinic as a location, which could mean that it has little experience running a clinical trial. As to why the company chose that clinic specifically, Andrews says he was “blown away” by the facility and staff.
How much gene therapy participants will receive is also unclear. Gene therapy involves administering genetic material into the body, usually via an injection or infusion. When asked, Andrews and Mathias wouldn’t comment on the exact dosage that Libella would be administering to study participants. “All I can say is, it’s a lot,” Andrews says. The gene therapy will be delivered through an IV for those in the anti-aging and ischemia studies and an injection into the spinal fluid for the Alzheimer’s study.
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Gene therapies are being investigated to treat a number of genetic diseases and cancers, and a handful of these therapies are on the market already. The hope is that these therapies could be given just once as a long-term treatment or potential cure. Most gene therapies use engineered viruses to carry a therapeutic gene to cells. Viruses are used for their ability to get inside a cell. These viruses are modified in a way so that they can’t transmit disease to people. But that doesn’t mean they’re necessarily harmless. Gene therapies can cause immune reactions, especially in high doses, and an animal study published last year raised additional safety concerns about high doses of gene therapies. In 1999, a teenager named Jesse Gelsinger died from an immune reaction caused by a gene therapy.
“I think of this as a study where many things could go wrong,” Turner says.
Libella’s trial will require participants to stay at the Colombian clinic for 10 days after receiving the therapy so they can be monitored for any side effects. Andrews says the company has “everything in place” in case that happens. Scientists will then monitor the participants for a year, assessing the length of their telomeres and measuring other biological markers of aging.
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Telomeres become shorter as cells divide, which happens constantly over a person’s lifetime. Eventually, cells stop dividing, a phenomenon called cellular senescence that is thought to contribute to aging. Senescence and how to stop it are hot topics in the aging field right now, but most researchers in the field have moved on from the idea that short telomeres are the key to understanding or reversing aging, says Steven Austad, scientific director of the American Federation for Aging Research and a professor of biology at the University of Alabama at Birmingham.
“There are all kinds of things that can initiate cellular senescence, short telomeres being only one of them,” he says. For this reason, Austad is doubtful that Libella’s experimental therapy will have any strong anti-aging effects. “I don’t think there’s any great hope of success,” he says.
He points to a recent paper that found no link between telomere length and aging — including lifespan of the participants’ parents, cognition, and muscle health — in more than 261,000 people aged 60 to 70 of European descent. The paper concluded that “telomere lengthening may offer little gain in later‐life health status and face increasing cancer risks.”
Some researchers in the field are concerned that putting a lot of telomerase into cells could make cells divide more quickly and promote tumor growth, says Austad. Previous research has linked longer telomeres to increased cancer risk, with scientists finding that cancer cells tend to have more telomerase that most normal cells. But telomere evangelists like Dr. Michael Fossel believe that shortened telomeres are a cause of age-related diseases like cancer and thus, lengthening them could help protect against these conditions.
Fossel is founder and president of Telocyte, a biotech startup that is developing a telomerase therapy for Alzheimer’s disease. He says his company’s treatment is similar to the one Libella is testing, but it’s taking a different regulatory approach. Telocyte is working with the FDA to get approval for an initial clinical trial, for which it hopes to have initial results in 2021. He says the company will not charge people to participate and that he is worried about companies going outside the purview of the FDA to do these kinds of studies. “We’re afraid that something will go wrong, whether it’s from a safety or efficacy standpoint.”
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