For patients who’ve run out of other options, experimental, unproven therapies like stem cell treatments offer new hope. But how do you sort the scientifically legitimate from the dangerous?
Regenerative medicine is a controversial field, still in its infancy. There are academic researchers and major biotech companies testing key treatments in high-profile, vetted clinical trials — but there are also fringe clinics promising stem cell injections that can cure everything from Alzheimer’s disease to cerebral palsy, though they have no evidence to back up those claims.
Sketchy clinics pull people in with big promises and slick advertising — anecdotal testimonials posted in online videos on blogs or social media. But some also mimic more reputable scientific endeavors by posting their work on ClinicalTrials.gov — a federal repository that doesn’t always vet postings to ensure their protocols meet federal standards.
“It’s completely impossible for individual patients, even individual physicians, to evaluate the evidence underlying every therapy that’s out there and to make an informed decision,” said Sean Morrison, the director of the Children’s Medical Research Center at UT Southwestern and the chair of the International Society for Stem Cell Research public policy committee.
The Wild West of information has spawned a side project for many in the space: trying, desperately, to correct the record and help patients make good decisions. Some are simply volunteering their time and expertise to help sort out the science. Others are institutions that offer more legitimate treatments, like the Mayo Clinic, or that fund clinical trials in the area, like the California Institute for Regenerative Medicine.
Experts warn, however, that far more work is needed to help patients sort through the science — particularly since sketchy stem cell clinics can be dangerous. Legitimate resources are available for patients online, but it’s easier to stumble on misinformation than expert advice — even if you’re a top official at the Food and Drug Administration, said Peter Marks, who helms the agency’s biologics center.
On a recent trip to Florida, he walked by a stem cell clinic offering unproven therapies.
“I am a physician, and even I wouldn’t know if I was not educated to know,” Marks said. “Everything looks like: Wouldn’t this be an approved medical procedure, right? And wouldn’t you be getting an FDA-approved product?”
Stem cells are attractive to researchers because they can essentially replicate any cell in the body. The hope is that stem cell therapies will let scientists replace a patient’s damaged or lost cells.
But right now, there are very few proven and approved applications of stem cells.
But scientists are in the early stages of testing a whole host of other stem cell treatments. Researchers in Germany, for example, used stem cells to cure a boy’s rare skin disorder; now they are conducting wider clinical trials to see if the results can be replicated. Other evidence-based trials are looking at stem cells as treatments for diseases like diabetes and Parkinson’s disease.
“There’s only a handful of true stem cell therapies … that have good data to back up their efficacy,” says Timothy Caulfield, research director of the Health and Law Institute at the University of Alberta. “I’m hopeful for the future, but that’s where we are right now.”
Look up “stem-cell therapies,” however, and you’ll come across a whole host of advertisements and offerings from largely unregulated clinics — the kind some researchers call “snake oil salesman.”
These kinds of clinics try to sell one-size-fits all therapies. They market blood cells and fat cells as treatments for anything from Alzheimer’s to knee pain. Clinics will remove a patient’s fat cells, and inject them back in, claiming these are stem cells, when they often aren’t.
Patients who turn to these overhyped treatments have more to lose than the tens of thousands of dollars these therapies cost — some patients have been blinded or developed tumors after receiving these therapies.
The FDA has tried to regulate the industry — it’s brought lawsuits against several clinics selling unproven therapies and issued warnings to patients about unproven treatments. The Federal Trade Commission, too, has also sued or settled with several clinics for deceptive advertising of stem cell therapies and recently sent warning letters to clinics pushing stem cell therapies that treat Covid-19.
But the FDA has also struggled to clarify what it will accept and what it won’t when it comes to regenerative medicine. It didn’t offer guidelines on the issue until 2017, and it has struggled to enforce those rules, which largely requires clinics to follow typical drug development rules and protocols for rigorous clinical trials. The deadline by which clinics have to comply with those rules isn’t until May 2021
“Unfortunately, the FDA has been slow to enforce its own regulations, so they’ve tolerated the proliferation of unproven therapies,” said Morrison. “But the FDA … is getting more aggressive about enforcing their regulations.”
In a statement to STAT, an FDA spokesperson said the agency is still working to shut down clinics that put patients’ health and safety in danger.
“We are concerned that people may use these products with a false sense of security about their safety and efficacy. As such, the agency has stepped up its oversight of cellular and related products in recent years and has issued compliance actions, including numerous warning and untitled letters, and pursued litigation for serious violations of the law, including some involving patient harm,” the spokesperson said.
Several experts have also expressed concern over a lack of oversight on Clinicaltrials.gov, the federal repository overseen by the National Institutes of Health. Standalone stem cell clinics have registered their unproven stem cell therapies as clinical trials on the website, which could lead patients to believe they are running rigorous, clinical trials that have been reviewed by an Institutional Review Board. Even the company that the FDA sued and shut down for providing stem cell therapies that ultimately blinded people, U.S. Stem Cell, had trials listed on ClinicalTrials.gov at the time of the injunction.
The NIH told STAT in an email last year that each of the studies on the website is vetted by humans. A spokesperson also emphasized that the postings must include information about risks and benefits of trial participation, as well as a recommendation to talk to a physician. The NIH also said they were “exploring additional measures” to address the issues.
Experts can use their expertise to distinguish between a rigorous clinical trial and a poorly designed one, leading patients to an experimental therapy backed by scientific evidence. But patients might not have the scientific savvy to do the same on their own.
Stem cell clinics take advantage of the power of patient testimonials. One study analyzed 159 YouTube videos advertising unproven therapies and found that 91.2% of them featured a patient extolling the ways the therapy had helped them — only 4.4% of the videos mentioned whether the treatment was based on scientific research or publications.
“The use of an anecdotal testimonial narrative will overwhelm our scientific critical thinking.” said Caulfield, the University of Alberta researcher who was an author of the study. “Even if in the back of their mind the patient thinks, ‘Well, I don’t know if this is going to work or not,’ they see that testimonial with someone like them … saying it works for them — that can be a very powerful marketing tool.”
“We’re asking a lot of patients, right?” he added. “We’re going to ask them to tease out a good study from a bad study or a good journal from a bad journal.”
And patients clearly struggle with the decision. Several described to STAT the challenges associated with trying to evaluate the science on their own.
Maria Alducin, who has suffered severe neurological symptoms that she attributes to side effects of fluoroquinolone antibiotics, sought out stem cell therapies after conventional treatments failed her.
“I can read hundreds of articles … and there is all sorts of contradicting information,” she said. “It’s just very frustrating to see.”
Even patients who find legitimate clinical trials take on the burden of weighing the risks of the experimental treatments — it can be tough to decide whether or not to participate.
“Everything was so new to us about this,” said Jake Javier, who participated in a clinical trial for a stem cell transplant to treat spinal cord injuries at Asterias Biotherapeutics in 2016 after breaking his neck jumping into a swimming pool.
“We had no idea how my life would be from here on out or what kind of condition I would be in and we had no idea about what stem cells really were or what would happen, so it was a whole new world for us,” he added.
There are a handful of places — and even individual people — to whom patients can turn for help.
People like Paul Knoepfler, a stem cell researcher at the University of California Davis School of Medicine who spends his limited free time policing the internet for false advertisements and misinformation from rogue stem cell clinics.
He flagged an advertisement on the website for the science journal Nature that looked just like any other peer-reviewed research article on the website — but falsely claimed that a controversial type of stem cell could help the heart recover from a heart attack, which is unproven. Nature ultimately took it down.
Knoepfler also runs a blog called “The Niche” aimed at educating patients about stem cell research and therapies and guiding them to potential clinical trials. He keeps an updated web page of legitimate clinical trials for patients, does regular Q&A posts where he answers common patient questions and misconceptions, and responds to as many emails and comments as he can.
He stressed to STAT, and stresses to patients who reach out and visit the blog, that he is not a physician — his goal isn’t to tell anyone what to do, just to inform and direct them to appropriate resources. He’s especially careful when responding to patients who email him. He usually recommends they be cautious or consult with their physician.
When people ask about specific clinics that he suspects of hawking unproven treatments, he says he’s careful about how he responds. “Maybe to my knowledge they haven’t really published anything, or I’m already aware of some kind of negative side effect someone reportedly had when they went to that firm,” he said.
Knopfler also monitors his very active comments sections. He removes posts that promote specific clinics or unproven therapies, and weighs in on big issues in the field, like whether patients should be charged for undergoing an unproven procedure.
The California Institute for Regenerative Medicine, which funds stem cell research and clinical trials, has taken a different tack: using some of the same tactics rogue stem cell clinics use to promote their research.
They make videos and blog posts highlighting stem cell research and active, FDA-approved clinical trials they have funded, often including patient testimonials about the potential of evidence based stem cell treatments.
“We want to make sure that people understand that there are good clinical trials and there is good research, and then there’s this other element which has … almost no scientific rigor behind it,” said Kevin McCormack, senior director of public communications and patient advocate outreach at the California Institute for Regenerative Medicine.
“We just have to keep repeating our messages on blogs, social media, through videos, and working with as many other agencies and organizations and the media to highlight the difference between the good science and the bad science,” he added.
Although they promote FDA-approved clinical trials, they are careful to manage expectations. It’s unlikely any of these treatments will be a cure, but rather provide incremental improvements.
“Many of these clinical trials are basically experiments, and many of them are Phase One so it’s the first time any of this has been tested or tried on people,” said McCormack. “There’s a great deal of uncertainty on the part of patients, so the more we can explain what we do and what’s involved, then the more impact we can have.”
McCormack said he gets emails and phone calls nearly every day from patients seeking stem cell therapies. He tries to help as many as he can by seeking out reputable FDA approved clinical trials that can treat their specific medical issue — he doesn’t want to leave them to navigate Clinicaltrials.gov on their own. But he said often there is not an ongoing clinical trial for the patient’s condition.
“I just have to explain that there isn’t anything there, but then also put in some information about how you can, if you do find something that you think would be interesting … decide whether or not it’s a good clinical trial to be a part of,” said McCormack.
The Mayo Clinic also established a consultation service to help achieve the same aim. The Mayo Clinic Regenerative Medicine Consult Service helps patients and providers learn about available regenerative therapies and stem cell clinical trials relevant to their condition. Patients can make an in-person appointment, or, more often, call.
Nearly a third of the patients who consulted with the clinic ask about unproven stem cell therapies, one study of the visitors found. Consultants redirected these patients to resources explaining the risks associated with unproven therapies like those provided by the International Society for Stem Cell Research or recommended searching through therapies at Clinicaltrials.gov — the study did not mention if consultants warned about issues with the website.
Shane Shapiro, the medical director of the regenerative medicine therapeutics program at Mayo Clinic stressed to STAT that the goal of the clinic is not to help the patient find a stem cell therapy, but the best therapy for their condition. And many do end up with options, the same study of the visitors found.
“More often than not, when we have an informed discussion with the patient, we’re able to show them there are still treatments that are available to them … and sometimes [the] treatments that patients may be hunting for may not be the best option for them,” Shapiro said.
“Our job really is just to reach the patient at their level of understanding of their particular condition and of the regenerative therapy that they might be seeking out and make sure that they have all the facts and that they have all the science,” he added.