Six patients with dementia went to Mexico for an unproven gene therapy, a biotech CEO claims

Six patients with dementia traveled to Mexico last year to be injected with a gene therapy not authorized for use in the U.S., according to the CEO of a Seattle-area startup that wants to accelerate testing of unproven anti-aging medicines and views U.S. drug safety regulations as a hindrance.

At the heart of the project is a controversial biotech called BioViva, whose CEO had herself injected with an experimental gene therapy in Colombia and whose advisory board includes renowned Harvard geneticist George Church. It is part of a growing ecosystem of entrepreneurs and scientists, dreamers and schemers, who believe aging is not inevitable and aim to develop treatments to extend the human life span.

Last month, during a talk hosted by the National University of Singapore, the CEO, Elizabeth Parrish, divulged that she was eagerly awaiting data from a human study involving six patients who received an experimental gene therapy. On Friday, she told STAT the procedures were done last year in Mexico. If true, it would be the first known attempt to use the technique to treat age-related dementia, which is most often caused by Alzheimer’s disease.

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STAT set out to independently verify the accuracy of Parrish’s claims. While many key details could not be confirmed, including the identities of these six patients and how the purported treatment affected them, STAT found evidence that BioViva and partners were recruiting patients. A newsletter emailed by BioViva in 2019 said 10 patients over age 50 with mild to moderate Alzheimer’s were needed for a study of a gene therapy. The one-hour procedure, according to an FAQ linked from the email, would be done in Mexico City and involved a one-time injection.

The effort raises the specter of an overseas medical tourism industry targeting patients desperate to lengthen their lives and offering unproven treatments that would permanently alter the genetic code inside recipients’ cells.

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The idea for gene therapy — using an innocuous virus to slip a good copy of a gene into the DNA of people’s cells to correct a disease-causing mutation — was first published in 1972. After decades of fits and starts, including some deaths in experimental trials, the U.S. Food and Drug Administration finally approved one of these medicines in 2017. Since then, at least nine more gene therapies have made it to market, for treating certain kinds of cancer and a few rare genetic disorders.

Parrish considers aging to be a disease, one that might be treated in similar fashion — by supplementing people’s cells with bits of genetic code to lengthen their chromosomes, or supercharge muscle formation, or boost proteins that protect against oxidative stress. The basics of gene transfer technology have advanced sufficiently in recent years to be within reach of a small company like BioViva that wants to apply them to aging. But Parrish doesn’t want to wait the decades it might take to find out if these approaches actually work under the existing regulatory framework, which requires extensive laboratory and animal experiments before initiating costly human studies.

“The power of the technology is there, we’re just not able to harness it because nobody is able to raise the money to get these disruptive regenerative medicines into clinical trials,” Parrish told STAT in an interview. If it were up to her, the FDA would have a regulatory route that would allow doctors to take treatments that look promising in animal models and give them to willing patients. But since that doesn’t exist, sending patients overseas, and paying for their treatment is the next best thing in her view, because at least that jump-starts the process.

“With the first human data, that should be a banner to investors to come in and invest in the technology so the rest of the world can experience it,” she said.

Parrish founded BioViva in early 2015. Months later, according to an account she gave to a reporter for Outside, Parrish traveled to Bogotá, Colombia, where unbeknownst to her family, she received more than 100 injections of an experimental gene therapy intended to turn on an enzyme called telomerase. Telomerase is a protein that extends telomeres, a stabilizing cap found at the ends of chromosomes, and sometimes referred to as the “aging clock” because they get gradually worn down the older you get. When they get short enough, cells stop dividing. Boosting telomerase is a favorite approach among the anti-aging evangelists because cells that are functionally immortal — ones that can go on dividing forever, like stem cells and tumor cells — tend to express the protein at high levels.

This molecule, and its role in aging, had been discovered in the late 1970s by scientists Elizabeth Blackburn, Carol Greider, and Jack Szostak. Their work in algae and yeast cells later earned them a Nobel Prize. In the 1990s, scientists at the Bay Area biotech company Geron Corporation mapped the human gene for telomerase. Leading that team was a molecular biologist named Bill Andrews. Years later, he would design a virus packed with instructions to switch on telomerase for Parrish.

“I didn’t know at the time she was going to treat herself,” Andrews told STAT. But after she did, the two began making plans to open overseas gene therapy clinics under BioViva. By 2017 though, those plans had fizzled and Andrews licensed his technology to a different company, Libella Gene Therapeutics. Libella initially tried to recruit patients for a pay-to-participate test of its telomerase gene therapy, which it claimed was to be done in India, for treating mid- or late-stage Alzheimer’s disease. The expected cost for the first patient would be $11 million, Libella CEO Jeff Mathis told STAT in an interview in 2019.

That trial appears to have never taken place. Libella then attempted to recruit patients for a small trial in Colombia, this time charging patients $1 million for its telomere-repairing gene therapy. Company executives told MIT Technology Review it had recruited two patients, but in the interview with STAT, Andrews said no one has yet received the treatment. Mathis did not respond to phone calls or emails from STAT.

During that time, BioViva pivoted to bioinformatics. “That means we look at data from companies sponsoring studies and analyze it for them,” said Parrish. The main company BioViva works with is Integrated Health Systems, which markets itself as a broker connecting patients to a network of doctors operating outside the U.S. who are willing to provide unapproved treatments. On social media, IHS describes itself as “the gene therapy specialists.” On its website, IHS lists only one doctor, a radiologist named Jason R. Williams, who is also BioViva’s chief medical officer. He also runs a cancer immunotherapy practice in Mexico City called the Williams Cancer Institute.

In July 2019, BioViva posted a YouTube video, announcing that Integrated Health Systems was launching a study of telomerase gene therapy, and was looking for volunteers with symptoms of mild to moderate Alzheimer’s disease to participate. The video was also shared on Integrated Health Systems’ Facebook page. The following month, BioViva sent a newsletter to its subscribers, advertising the study, and saying that the $62,000 treatment would be offered free to participants, with the cost covered by Maximum Life Foundation, a nonprofit that funds aging research.

An FAQ document and sign-up form detailed that the study would be conducted at the Williams Cancer Institute in Mexico City. Participants would have to pay for their own travel. Once there, they would receive a single injection of the telomerase gene construct to “rejuvenate brain cells called microglial cells.” It was described as a one-hour procedure, but patients were advised to stay in the area for four to five days in the event of an adverse reaction. These documents indicate that IHS screened candidates in the spring of 2019, and planned to schedule the treatments between April and October of that year.

IHS described candidates as otherwise healthy individuals over the age of 50 with a probable Alzheimer’s diagnosis and a reliable caregiver to accompany them to the study site. “Please note that it is critical that you commit to the entire process so that this study can provide credible results to move into larger populations,” the FAQ states. “It is an honor to have you apply and participate.”

The language of these materials, touting potential cures and working therapies, were both misleading and manipulative, said Leigh Turner, a bioethicist at the University of Minnesota who studies medical tourism and reviewed the documents for STAT. Under regulated clinical research, investigators would be required to disclose an approved study design and methodology to the public in a database like clinicaltrials.gov before recruiting participants. Such a listing should describe what patients will be receiving, and how much, and how often, and how it will be administered, where it will be administered, what metrics will be used to determine if the treatment worked, and what the rules are for stopping if something starts to go awry. Nearly all of that was missing here, he said.

“Everything I’m seeing indicates the involved parties are not conducting a credible clinical trial with appropriate safeguards,” said Turner.

IHS did not respond to STAT’s emailed questions. No phone number is listed on the IHS website, and no contact information is registered to the domain. In response to requests for more details about the company, Parrish referred STAT to IHS’s generic information email address. Dave Kekich, the president and CEO of Maximum Life Foundation, who is also director of strategic planning at BioViva, confirmed to STAT that IHS had treated six individuals, and said they had to show they had symptoms of dementia.

“This is an offshore medical tourism operation to test an experimental therapy,” he said. He referred questions about study specifics to Williams.

Emailed questions sent to Williams and his assistant in Alabama did not receive a response. A STAT reporter went to the Mexico City hospital listed as Williams’ affiliated inpatient facility, and verified through another radiologist there that Williams performs immunotherapy treatments at the hospital, but not gene therapy treatments, to this doctor’s knowledge. STAT identified three U.S. cancer patients who said they traveled to Mexico for immunotherapy treatments from Williams, after raising money via GoFundMe campaigns to pay for the procedures, which they described as costing between $100,000 and $120,000.

Williams has a history of providing unapproved treatments to desperate patients. In 2012, he opened a practice called Precision StemCell, which offered unproven stem cell treatments for everything from spinal cord injuries to ALS to inherited childhood blindness. Later that year, Turner wrote a letter to the FDA, asking the agency to intervene. Williams told MIT Tech Review in 2015 that he’d ceased providing those treatments in the U.S. in 2013, after the FDA asked him to stop because they required agency approval. He later established a clinic in Bogotá, Colombia, and launched a company called Neuralgene that claimed it was testing gene therapies for ALS delivered to the spinal cord. According to its website, Neuralgene has since relocated to Mexico along with Williams, who is listed as its CEO and director of R&D. No other employees are listed.

Parrish and Williams have known each other for years though rarely spend time together. She confirmed to STAT that he was the one who injected her with DNA-modifying viruses back in 2015. And the two appear in videos together on BioViva’s YouTube channel, talking about genetic approaches to staving off different aspects of aging — him beaming in a dark wood-paneled office, her floating in front of an ethereal black and gold background. During these conversations, Parrish often name-drops research the company is doing with Rutgers University. In other videos, she also mentions Harvard’s Church.

In 2018, BioViva began funding work in the Rutgers lab of microbiologist Hua Zhu, who studies herpes viruses. For the last few years, his team has been doing experiments in mice with one of these viruses in particular — a recombinant cytomegalovirus — to test it as an alternative gene therapy delivery system, or vector, to the more commonly used adeno-associated viruses (AAVs). In work that has not yet been published, Zhu’s team loaded up the cytomegalovirus with anti-aging gene targets, including telomerase. Compared to mice that didn’t get the treatment, these mice lived about 40% longer, he told STAT. “That’s very significant,” he said.

Church, who confirmed to STAT that he is still a scientific adviser to BioViva, said he has been involved in Zhu’s mouse research and is a co-author on the paper Zhu’s team is preparing. And though he is aware that BioViva has been interested in pursuing clinical trials of telomerase gene therapy for a while, he said he was not aware that the company’s partners had paid for people to receive those treatments in Mexico.

In 2015, Church’s lab accepted and analyzed some of Parrish’s blood samples from the Bogotá experiment. When asked whether his lab has received any samples or patient data from the six patients in the IHS dementia study, he said, “No, we have not.”

Turner, the bioethicist, is concerned that celebrity scientists like Church are lending credibility to an operation that might be putting people in harm’s way. “You don’t want to have academics at reputable institutions offering a protective function for what appears in many ways to be pretty disturbing activities on the part of these companies,” said Turner. ”So if he’s going to lend his name to businesses like this one, in a way, he becomes responsible for propping them up.”

Asked about Turner’s comment, Church wrote in an email: “Is helping a bit with a (quite different) mouse experiment at Rutgers … somehow ‘offering a protective function’?” He added that he has “stressed support for proper clinical trials in the past, and I still do.”

On Monday, after this story was posted, Church emailed to say he had reached out to Parrish: “I do feel that the critique seems fair and hence have contacted Liz to try to get additional clarification and potentially change some aspects,” he wrote.

One thing that’s still unclear is where IHS is obtaining the virally packaged genetic material needed for the treatment. Zhu said that his lab does work only in mice, and that he was not involved in creating vectors for any human studies. Virovek, a California biotech company that produces much of the AAV vectors used by American academic research institutions, did not answer questions about whether any treatment had been produced for IHS or Williams.

Parrish also denied that BioViva provided them. “We don’t have the capacity to manufacture vectors,” she said. Her team’s role in all this, she said, is to analyze the patient data from the six trial participants. She said she expects to have results from their eight-month follow-up to share with the public in early June.

“I am dying to see the data,” said Andrews. Even though he’s a BioViva competitor now, he wants to finally, after all these years, see a proof of concept. “I really hope they did it,” he said.

But not everyone involved is so enthusiastic.

“Telomerase has been shown to be rejuvenating in animals,” said Church. But is the science mature enough to move into humans? That’s more complicated. One of the concerns is that telomerase can convert healthy cells into indefinitely dividing malignant ones, causing cancer.

“I think that’s still an issue with telomerase. I would not sugar-coat that,” said Church. “So I’m not sure it is time for that just yet, but it’s close. It’s extremely close.”

Olivia Goldhill contributed reporting from Mexico City.

Source: STAT