Umbilical cord blood samples are seen during microbiological tests at the headquarters of the Polish umbilical cord blood bank PBKM/FamiCord on November 26, 2019 in Warsaw. Photo via Getty Images
When desperate parents are looking for medical treatment for their kids, especially their autistic kids, they often do two things: They look up information about a program at Duke University, and then, in short order, they go to GoFundMe. The fundraising site is full of pleas that often mirror one another, in essence saying: My child has one hope, and that hope is in stem cell and cord blood treatments. This hope, though, is attached to treatments that are hotly disputed at best, unproven at worst, and often very expensive in either case. At Duke University’s Marcus Center for Cellular Cures, parents can enroll their children into a number of clinical trials that aim to study the effects of cells derived from umbilical cord blood on treating the effects of autism and brain injuries; adults can also participate in a trial testing whether cord blood can help them recover from ischemic strokes. And when parents can’t get their children into any of these clinical trials, particularly for autism, they often opt for what’s called the Expanded Access Program (EAP), in which they pay between $10,000 and $15,000 to get their kids a single infusion. All of the trials use products derived from human umbilical cord blood, which is a source of stem cells as well as other types of cells. The autism trials are using a type of immune cells called monocytes, according to Dr. Joanne Kurtzberg, a well-respected Duke professor who’s conducting clinical trials into whether cord blood can help with autism, and who has been researching stem cells since the early ’90s. (On ClinicalTrials.gov, however, these trials are listed as using mesenchymal stromal cells, which are a completely different type of cord blood cell.) Now, a for-profit company called Cryo-Cell International with ties to Duke researchers has indicated that it plans to open clinics promoting these treatments, under a licensing agreement with the renowned North Carolina university. (Cryo-Cell acknowledged receiving a list of questions from Motherboard, but did not respond to any follow-up emails or respond to those questions before publication.) In their investor presentation, Cryo-Cell said they plan to become “an autonomous, vertically integrated cellular therapy company that will treat patients.”
Duke and Cryo-Cell’s rush to monetize a procedure before it’s shown to have solid benefits has created concern, though, across the community of scientists, clinicians, and medical ethicists who study autism treatments. The hope is that these cord blood infusions can improve some autism symptoms, like socialization and language, or decrease the inflammation that some parents and clinicians think might exacerbate autism symptoms. Early study results, however, haven’t been very promising. A large randomized clinical trial, the results of which were released in May 2020, showed that a single infusion of cord blood was not, in the words of the researchers, “associated with improved socialization skills or reduced autism symptoms.” This is why Duke’s latest move comes as such a surprise: The university and Cryo-Cell have told investors that they’re planning to open a series of “infusion centers.” At these clinics, Cryo-Cell will use Duke’s technology and methods to offer cord blood treatments for $15,000 per infusion.In an exuberant presentation for investors, Cryo-Cell said it estimates an annual revenue of $24 million per clinic; it hasn’t disclosed how many clinics it plans to open. At least one will reportedly open in Durham, North Carolina.
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The move follows a June 2020 announcement that Cryo-Cell had entered into an exclusive patent-option agreement with Duke, allowing it to manufacture and sell products based on patents from Dr. Joanne Kurtzberg. Thus far, though, Duke’s trials have not shown any promising results for cord blood products as autism treatments, granting that the research is still far from over. The university told Motherboard, “Duke’s institutional position is that additional research is required and to encourage further study to provide definitive results.” (Many autistic self-advocates object to the idea that autism needs a “cure,” and elsewhere, autism research is beginning to shift away from that language and more toward early diagnosis for children and helping autistic adults lead fulfilling and fully supported lives.) Kurtzberg's goal, she told Motherboard in email responses provided by Duke, "is to develop and evaluate treatments that will help improve social skills and the ability to communicate with others in children with autism.” For both cerebral palsy and autism, she added, “improvements are measured using well-established tests. Among some children with cerebral palsy, improvements have been measured in gross motor function. With autism, there have been measurable improvements in communications and executive function among some study participants.” Alycia Halladay is the chief science officer at the Autism Science Foundation, which seeks to guide families into safe, evidence-based treatments for autism. “While stem cell therapies as medical intervention for the ASD are currently being rigorously studied at Duke, it is still too early to say they actually help those on the spectrum,” she told Motherboard. “Making the move at this time to sell this therapy to families across the world is irresponsible and dangerous. It shocks and surprises me that Duke University, an institution with a stellar academic reputation, would enter into an agreement to sell intellectual property for stem cells in autism, especially since Duke has enormous financial incentive to make this profitable for Cryo-Cell.”“I was horrified when I first heard about the Duke program,” said Anne Borden King. She’s a Toronto-based science writer and the current chair of the Campaign Against Phony Autism Cures. She also hosts the podcast “Noncompliant,” about neurodiversity, where she’s frequently spoken critically about the Duke program. Borden King has come to believe that Duke is leveraging its reputation to run a program that’s far from ethical. “When you see a university name on a project, you think everything must be on the up-and-up,” she said. “But that’s actually not a safe assumption. Money talks.” The idea of using therapies derived from umbilical cord blood to treat serious disorders isn’t new, and neither is the controversy around it. There are small stem cell clinics across the world, from Mexico to Panama to the Caribbean, making a host of shaky claims about the benefits that stem cells from cord blood can provide, both autologous ones (stem cells that come from the patient themselves, taken from cord blood banked at birth) and allogeneic (stem cells that come from someone other than the patient). In the past decade, small stem cell clinics have also begun to dot the United States, mostly in strip malls and similarly downmarket locales, offering treatment for things like back pain. Stem cell clinics started to bubble into the public awareness around 2010. At that point, said Paul Knopefler, “almost all of it was outside the United States. I had people asking me, ‘Should I go to the Caribbean?’”Knoepfler is a professor at UC Davis in the Department of Cell Biology and Human Anatomy. For the last 11 years he’s also been one of the more widely-read experts on stem cell and related therapies, with a blog called The Niche. He’s watched as these treatments went from speculative to potential cash cows; one of the earliest clinics to get a flood of attention was Celltex, a Texas firm where former Gov. Rick Perry had experimental back surgery. (NBC reported in 2011 that Perry pushed a bill that would have benefited Celltex, and he joined its board of directors in 2016, after he was no longer governor but before he joined the Trump administration as energy secretary. Perry resigned from that position in 2017.) In the early days, Knoepfler said, “it was a mixed bag in terms of the diseases that were on people’s minds: arthritis, orthopedic issues, ranging to things more concerning to me, like parents reaching out about kids with autism or cerebral palsy.” In the mid 2000s, agreed Leigh Turner, “I was watching this entire marketplace come into existence before my eyes.” Turner is a bioethicist and a professor in the Department of Health, Society and Behavior at UC Irvine’s public health program, and he and Knoepfler released a study in 2016 showing a huge profusion of stem cell clinics across the United States, often marketing themselves as cures for orthopedic and sports medicine problems. What they found, Turner said, was “a growing number of companies in the U.S. that were selling purported stem cell treatments not licensed by the FDA, [and which had] no meaningful evidence of safety and efficacy.” He wrote a letter to the FDA about one such clinic, urging it to investigate, before realizing that looking at the field as a whole would be a better use of his time.
A student walks past Duke Chapel on the campus of Duke University in Durham, North Carolina, Monday, April 30, 2007. (Photo by Jim R. Bounds/Bloomberg via Getty Images)
Though stem cell clinics have been around for years, the sheen of academic and scientific legitimacy bestowed by Duke onto experimental stem cell and cord blood treatments is very new indeed. And the combination of legitimate institutional backing, money, and the hopes of desperate parents is creating a combination that critics say is combustible and potentially very risky. At Duke, Turner said, there are respected researchers like Kurtzberg, who have, as he put it, “a long period of actual research in stem cell transplantation and meaningful research in publications, credible clinical trials. These are actual individuals who are part of the broader scientific community. It’s not the veneer of science. I imagine there are cell manufacturing and cell processing techniques that are more robust than you’d get at a strip-mall stem cell clinic.” But there are also some similarities between what Duke is doing and the work at smaller clinics, he added. “One of them is that, at the end of the day, there are many individuals paying out of pocket. It’s not just a clinical trial. Not covered by a public or private health insurer.” Kurtzberg is also now the medical director at Cryo-Cell, a position she took on in 2018. (A Duke spokesperson confirmed that she’s still in that role. In response to a question about how the university manages potential conflicts of interest between Kurtzberg’s two roles, they told Motherboard: “All Duke faculty must observe conflict of interest guidelines that are closely monitored by the university. Dr. Kurtzberg has reported activities with companies, institutions, or organizations outside Duke University. Any potential conflicts of interest are reviewed and, when appropriate, managed by the individual and the university.”) Kurtzberg, in email responses provided by Duke, said that her role at Cryo-Cell was the result of the company acquiring a cord blood bank called Cord:Use, which contracted with a blood bank she founded at Duke. “When Cryo-Cell bought Cord:Use, those functions and financial arrangements continued without change.” Her salary for that job, she said, “was paid directly to the Family Support Program for the Pediatric Transplant and Cellular Therapies” at Duke.As the cord blood market has grown, autistic children—and their often desperate, always well-meaning parents—have since begun to comprise a core market for those therapies, even as the benefits of the treatments remain largely speculative. And as Business Insider’s Tom Porter reported in January, experts in the field say that the fly-by-night clinics in other countries are getting an unintended legitimacy boost from Duke. In GoFundMe appeals, parents talk about going to overseas clinics after being unable to get into Duke, or because they felt they saw promising results from a Duke infusion and wanted another. “We have researched hospitals outside of the United States and there is a reputable medical group performing the Stem Cell Therapy in Panama City, Panama,” reads one typical plea, from a desperate mother, asking for $20,000 to get her child there. Autistic kids and their parents are already extremely vulnerable from the start, Borden King says, due to the sheer amount of misinformation and pseudoscience that’s directed their way. She began running the Campaign Against Phony Autism Cures three years ago, after her son received an autism diagnosis. “I started meeting all these parents in meetup groups who were doing phony cures and it really shocked me, just how much of it is out there, how many different scams,” she said. “How dangerous some of them are for kids. Things like feeding kids bleach, using chelation to remove so-called ‘vaccine injury,’ and so many other things.” She began looking at the Duke program after seeing the results of the study released in May 2020, which showed that a single cord blood infusion wasn’t effective in reducing autism symptoms. (The study authors, Dr. Kurtzberg and her colleague Dr. Geraldine Dawson, did say, however, that a subgroup of children in the study without an intellectual disability showed some improvements in “language communication, ability to sustain attention measured via eye tracking, and increased alpha and beta EEG power, a measure of brain function,” as a press release from Duke put it.) The results were unambiguous overall, in the view of experts in the field. “This is a uniquely solid study in this area so in my view there’s not much room for hedging bets like ‘Well, maybe trying things a little different will work’ anymore,” Paul Knoepfler wrote on The Niche. “The key data in the paper are in Table II (screenshot below) showing across the board that there is no benefit of cord blood for these patients.”“The first thing that jumped out at me when I read Duke’s study was they reported kids having health issues during infusion, like severe allergic reactions—and also being agitated and upset by the procedure,” Borden King said. (Duke’s researchers said some children experienced “agitation during IV placement and infusion” and one child experienced an allergic reaction, which was immediately treated, but they characterized most of the adverse events seen during the study as “nonserious,” and that overall the infusions were “safe and well tolerated.”)
Umbilical cord blood and cord, collected from hospitals, are prepared for storage at the headquarters of the Polish umbilical cord blood bank PBKM/FamiCord on November 26, 2019 in Warsaw. - Poland has emerged as Europe's leader in stem cell storage, a billion-dollar global industry that is a key part of a new therapy that can treat leukaemia but also raises excessive hope in other patients. (Photo by Wojtek RADWANSKI / AFP) (Photo by WOJTEK RADWANSKI/AFP via Getty Images)
The second thing, Borden King added, was “Duke’s own conclusion that they didn’t find any benefit from the infusions. The third thing was that they were continuing with new studies of the same thing and running a pay-to-play [in the form of the EAP program]. I thought, why? Their own studies say no evidence of benefit and clear evidence of harm. Why are they continuing?” (Duke told Motherboard, “Further research is warranted to understand the basis for favorable responses in some study participants,” referring apparently to the subgroup of children without intellectual disabilities.) There’s one main reason why Duke has been able to run so many clinical trials relating to stem cells: Bernie Marcus, the Home Depot founder. Marcus suffered from bronchiectasis, a condition where the lungs become damaged and clogged with mucus, and sought treatment from the Stem Cell Institute (STI) in Panama, according to a blog post on its website. STI is controversial, to put it lightly. The physician and science writer Dr. David Gorski, who writes frequently about pseudoscience, especially in autism treatments, has baldly referred to it as a “quack clinic,” noting that their website “advertises stem cells to treat autism, cerebral palsy, heart failure, multiple sclerosis, osteoarthritis, rheumatoid arthritis, spinal cord injury, and autoimmune diseases, complete with very little actual science but a whole lot of testimonials.”
Duke told Motherboard that “‘Cures’ is an aspirational term, not a statement about the current standard of care.”
Marcus felt that the treatment he received in Panama helped his condition; soon, per the STI blog post, he was bringing his wife down to Panama for treatment to help with her knee pain. His foundation, the Marcus Foundation, soon began donating millions of dollars to both STI and Duke for stem cell research. (The Marcus Foundation could not be reached for comment: the non-profit does not maintain any kind of public-facing website or social media presence, and a phone number for them does not allow callers to leave messages. Several messages to the organzation’s program director, Elisa Levy, were returned as undeliverable.) Bernie Marcus’ efforts in this area led, in 2018, to the founding of the institution at Duke that bears his name: the sunnily named Marcus Center for Cellular Cures. “I think [that name] is hugely problematic,” says Jeremy Snyder, a professor in the Faculty of Health Sciences at Simon Fraser University whose research focuses on public health ethics and medical tourism, among other topics. (He and Leigh Turner have released research about misleading stem cells claims in GoFundMe appeals and the ways platforms like GoFundMe can spread health misinformation across the web. “In general crowdfunding platforms, they appear to be do very little in terms of any way vetting crowdfunding campaigns, Turner told Motherboard. “It can be a dodgy cancer clinic in Germany or a stem cell clinic in the U.S. and GoFundMe takes a hands-off approach unless there’s a groundswell of media coverage.”) “That’s a longstanding complaint,” Snyder says, of the Marcus Center’s incredibly optimistic name. “You’ll see this in the cancer realm quite a bit. Marketing divisions of large hospitals put out commercials and different marketing materials, and you get a lot of that misleading language, playing on these tropes of hope, fighting, cures.” The point of the research, he explained, isn’t necessarily to “cure” the participants. “It’s to find out if this thing even works. If you’re getting ahead of yourself and calling it a cure, that’s deeply unethical.” (Duke told Motherboard that “‘Cures’ is an aspirational term, not a statement about the current standard of care.”) In email responses provided by Duke, Kurtzberg told Motherboard that monocytes “can modulate inflammation, especially in the brain. In cerebral palsy, these cells promote repair of myelin—particularly in the motor tracks, which is often damaged during injuries. We have published several papers regarding this, noting the unique properties of monocytes in cord blood.”Autism, Kurtzberg added, “is more complicated because there are multiple etiologies causing this condition. In some instances, there is inflammation of the brain, and cord blood tissue appears to calm down that inflammation in animals and lab models. We are exploring whether cells in cord blood or in cord tissue, we’re not sure which, has the ability in certain patients to calm down that inflammation and improve symptoms.” This theory, though, is not new. As journalist Brendan Borrell reported in an extensive investigation for Spectrum News in 2019, Kurtzberg and Geraldine Dawson led a Duke team that published results in 2017 suggesting that in a trial of 22 children, all between 2 and 5 years of age, 13 had shown improvement after a single infusion. But, as Bournell noted, “Without a control group, it is impossible to say whether the children would have improved anyway.” More importantly, he wrote, “A follow-up report found that those who improved showed increased connectivity in brain regions affected by autism, including the limbic system, but the researchers published no evidence to support their inflammation theory.” As the years have passed, Turner, Knoepfler, and Snyder have all begun asking the same basic question about the Duke program: Why is an intervention that hasn’t shown much in the way of results not only still operational, but also charging participants a lot of money to get access to it? “We can look at their own research,” Turner said. “They haven’t done a convincing job of demonstrating efficacy. So should people have to pay what can end up being substantial amounts of money?” Knoepfler has questions, he said, about whether the FDA is “carefully monitoring” the Expanded Access Program at Duke, which it does have to approve, at least initially. “Are they still aware Duke and Cryo-Cell want to expand this greatly?” he asked. “Is the FDA aware of the fact that hundreds of kids have gotten infused and the plans could be for thousands more? That’s where I don't have a good sense. A lot of these things are hard to tease apart. There’s different confidentiality issues.” One especially tricky thing, he added “is that Duke must have gotten what’s called an IND, or investigational new drug applications, for cord blood or stem cells related to cord blood. That’s the basis for running a clinical trial. And anything related to an IND, the FDA views as confidential.” Indeed, in investor documents, Cryo-Cell says plainly that it plans to administer stem cell infusions under the permissions granted by Duke and Kurtzberg’s IND approval. It has gotten, Cryo-Cell’s documents add, $5 million in startup funding from the Marcus Foundation. The FDA did not answer specific and detailed questions about Cryo-Cell’s planned infusion centers, telling Motherboard, “As a general matter, FDA cannot comment on particular applications or investigational products.” But in order to charge patients for an investigational drug under an IND application, the agency added, “the sponsor must obtain prior written authorization from FDA in accordance with FDA regulations. When charging for individual patient expanded access [sic] to an investigational drug, a sponsor may recover only its direct costs associated with making the drug available to the patient. For individual patient expanded access, the sponsor may not charge for indirect costs, including administrative costs associated with providing an investigational drug.”
Home Depot CEO Bernie Marcus poses for a portrait in a Home Depot store October 15, 1998. (Photo by Erik Lesser/Liaison)
The FDA also told us that stem cell therapies and other similar treatments carry some innate risk, and essentially warned that the buyer should beware:
“Anything related to an [investigational new drug application], the FDA views as confidential.”
The agency also said it has sent warning letters and “pursued enforcement actions for serious violations of the law” related to stem cell clinics. To date, a spokesperson wrote, it has sent “400 letters to manufacturers, clinics and health care providers, noting that it has come to our attention that they may be offering unapproved regenerative medicine products and that their activities may be subject to FDA regulation.” In a recent blog post on The Niche, Knoepfler called on the FDA to freeze Duke’s EAP and closely examine its deal with Cryo-Cell. “The big-picture reason that I believe the agency should freeze this EAP is that it is not in the best interest of the children and their families,” he wrote. “I believe that Duke and Cryo-Cell may be too focused on ultimately profiting off of the EAP in the long run rather than just helping children.” The science, he added, is simply not there. “Keep in mind,” he wrote, “there is no good evidence that cord blood can help kids with autism or CP. EAPs of this kind are supposed to have at least some quality data that is encouraging. I don’t see such data in this case.” There’s also evidence that Cryo-Cell plans to extend these unproven treatments to COVID-19, which would both expand its market share and crowd an already cluttered marketplace of questionable treatments for the disease.With funding from the Marcus Foundation, Duke is already running Phase 1 and 2 trials to see if mesenchymal stromal cells, which are also taken from cord blood, could help treat Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. Those results are not expected until 2022, but as has become a pattern with Duke and Cryo-Cell’s partnership, they’re already selling investors on the idea: Cryo-Cell’s pitch deck to investors says there are “indications under current clinical study” that mesenchymal cells from cord tissue could be used against both autism and COVID-19. (The FDA told Motherboard the agency has not approved “any regenerative medicine products, including stem cell therapies, for the treatment of COVID-19, multiple sclerosis, or autism. The only stem cell–based products that are FDA-approved for use in the U.S. consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood.”) Halladay, of the Autism Science Foundation, told Motherboard she has simple advice for families looking at these treatments for autistic kids. “Families should not consider this an established, evidence-based treatment,” she wrote in an email. “Families hearing about this plan by Cryo-Cell should be suspicious and turn to their doctor or clinical team for other potential treatments and treatment combinations. This may include not just for core autism symptoms but for debilitating mental health comorbidities as well.” In the end, the issues here extend beyond just Duke, and even the world of stem cell research, Borden King argues, noting they touch on the very nature of scientific credibility itself. “When people think of pseudoscience, they tend to think of things like a cheesy salesman selling fake pills online,” she said. “But in my work, I see quite a few examples of autism scammers hiding behind university credentials, building hype through a university. This all has a broader impact on the credibility of our universities, which are supposed to be grounded in science. Especially at this time, when we’re fighting a pandemic and we need clear boundaries around science versus pseudoscience, the impact of projects like this just really ripples out.” A full statement from Duke University is below:
Stem cell therapies offer the potential to improve human health, but they also create potential inherent risks for patients because of the way they may be manipulated or administered. Unproven/unapproved stem cell therapies can be particularly unsafe and have led to serious infections, blindness, and death. There are companies that are making unsubstantiated claims about the potential benefits of unproven cell therapies and their use in regenerative medicine, which is a disservice to those innovators who are working to develop safe and effective stem cell products, fully in keeping with our statues and regulations. Actions like this cast doubt across the entire field of regenerative medicine. We are concerned that people may use these unapproved products with a false sense of security about their safety and efficacy. Consumers should be cautious of any clinics, including regenerative medicine clinics, or health care providers, including physicians, chiropractors, or nurses, that advertise or offer any of these products.
Researchers at Duke University have studied the use of cord blood cells for pediatric blood cancers and have explored potential therapeutic applications of these cells for neurological disorders in children arising from inborn errors of metabolism, traumatic brain injury, cerebral palsy, autism and neuroinflammatory conditions.
Duke researchers are active in conducting randomized controlled clinical trials evaluating cord blood cell therapies for these applications. Data from the studies are submitted for publication in peer reviewed journals and are rigorously assessed by the scientific community and the FDA. Much remains to be learned about how these cells affect the brain and about clinical outcomes, and Duke investigators are committed to ongoing research to close these gaps in knowledge.
For some children who do not qualify for clinical studies, but who have few other options for treatment of their conditions, the FDA has authorized Duke to offer cord blood cells through an expanded access protocol (EAP) monitored by the FDA.
In recent months, Duke has entered into a licensing agreement with Cryo-Cell International to provide regulatory information and other data that would help advance the company’s effort to develop a cell therapy program eligible for approval from the FDA. This licensing agreement does not grant Cryo-Cell the use of Duke’s EAP for the treatment of patients at Cryo-Cell, but will allow Cryo-Cell to develop its own cell therapy program.
Duke is committed to ensuring that scientific evidence guides the further study and use of these investigational therapies. As new findings provide additional insights, Duke will continue to evaluate how best to move forward, both with research and with FDA-approved clinical applications.