“Pay to Play”: Pt 4 of The Rise and fall of “stem cells for autism” at Duke University
This is the fourth in a series about Duke University’s experiments on autistic children, in which young children, including those with IQs below 70, were injected with stem cells to see if it would stop them from being autistic. This series looks at the 9 years from first FDA approval in 2014, to the addition of Expanded Access (EAP) “pay to play” clinical trials, to pushback from experts and finally the cancellation of the EAP in 2023.
“Compassionate care” or exploitation? Duke’s pay-to-play stem cell program
In June of 2020, as the world was reeling from the early waves of the pandemic, a team of researchers at Duke University granted stem cell company Cryo-Cell exclusive patent rights to Duke’s biologics procedure if researchers could provide proof that stem cells could treat autism (Spoiler alert: They did not.)
The agreement granted Cryo-Cell the “rights to proprietary processes and regulatory data related to cord blood and cord tissue developed at Duke, [making] Cryo-Cell the only cord blood bank with the right to offer treatments to children at its own infusion clinic under Duke’s FDA-approved Investigational New Drug Application.” In 2020 and 2021, Cryo-Cell broke ground for new clinics that promised to deliver the proprietary procedure for a fee, if it became approved by the FDA. (Spoiler alert: It has not been.)
In 2020, a precedent had already been set to charge families tens of thousands of dollars for this unproven and risky treatment. The Duke team--whose project lead, Dr. Joanna Kurtzberg, was also the Medical Director for Cryo-Cell--had already secured Expanded Access Project (EAP) approval from the US Food and Drug Administration (FDA) to charge parents a whopping $15,000 to have their children enrolled in their experiments, which had previously been sole-funded by Home Depot co-founder Bernie Marcus.
Concerns and questions
As I’ve documented throughout this series, stem cell biologists as well as bioethicists and members of the neurodiversity community were concerned about the ethics of charging families for this expensive, experimental and implausible treatment. A central question swirled around us: Was Duke selling an opportunity for a groundbreaking medical miracle or merely peddling false hope?
FDA approvals for the Duke team’s Expanded Access Program (EAP) just seemed really, really odd, given that FDA regulations state that EAPs (which allow researchers to charge study participants for study costs) since the FDA’s own documents state that EAPs apply only to experiments related to conditions where there is no standard of care and where the condition is life-threatening. The thing is, there are standards of care for autism, and autism is not a life-threatening condition. Furthermore, the Duke team’s research was being done on vulnerable subjects (children).
Another hazy area was around conflict of interest. Kurtzberg’s leadership role at Cryo-Cell was a conflict of interest—when a researcher has two or more duties that are incompatible to ethical conduct of research (where one cannot be fulfilled without compromising another). But because Duke is a private school, there is no publicly-available information about whether and how Kurtzberg disclosed these conflicts of interest to its Institutional Review Board (the committee that reviews the ethics of research involving humans), nor whether the conflicts of interest were disclosed to parents, nor how the IRB responded to the conflicts of interest.[1]
A dedicated clinic--promised, then deferred
In a 2021 investor pitch, Cryo-Cell told its investors the company anticipated a return on investment (ROI) of $24 million per year once their dedicated stem cell infusion clinics were up and running,[2] suggesting to investors that “indications under current clinical study” show that stem cells could and would be an autism treatment.
A September 2021 headline in a Triangle Business Journal trumpeted: “Stem cell firm that partners with Duke University grabs space in Durham.” In 2021, Cryo-Cell received $5 million in startup funds from Marcus, who endowed a centre and earmarked another $26 million for more stem cells trials at Duke. The concrete was being poured, so to speak, for multiple centres, all with a confidence that the FDA would support Duke’s project to the extent that hundreds or thousands of children would be brought to Cryo-Cell’s clinics, and their parents billed accordingly.
Cryo-Cell’s website in 2021 had announced the launch would take place in 2022. Then in 2022, a launch was announced for 2023. Both websites described Cryo-Cell as “the only cord blood bank with the rights to establish infusion clinics to further advance investigational therapies developed at Duke,” stating:
“Currently these therapies are offered to patients at Duke under the FDA Expanded Access program, but there is an extensive waitlist. However, with our clinic's anticipated opening, we hope to alleviate the wait time and expedite treatment options. Treatments include the use of cord blood to treat conditions such as: Cerebral Palsy; Autism; Brain Injuries; Other Neurological Disorders.”
“Dr. Kurtzberg nicely sums up the hope that lies in cord blood to treat autism,” the Cryo-Cell marketers concluded, pointing to the fact that stem cell research is “27 years young.”
Stem cell expert Paul Knoepfler, who had been meticulously documenting the situation at Duke on his website, The Niche, noted at the time of the Cryo-Cell announcements that the partnership “seems to be heading in a worrisome direction.” He wrote in 2021:
“Their plans remind me of unproven stem cell clinics in several ways. I believe the FDA needs to take a close look at what’s going on and maybe put a hold on the expansion plans.”
The puzzle of the FDA approvals
The Duke team had concocted a pay-to-play project, gaining Trump-era FDA approval to run an Extended Access Program (EAP) that charged desperate parents a fee of roughly $15,000 per infusion.
It is unclear why the FDA approved the project. As mentioned, the agency’s own guidelines specified clearly that expanded access can only be used for life-threatening conditions where no other treatment is available. Despite the fact that there are standards of care for autism—the Cryo-Cell/Duke EAP continued[3]. More than 200 autistic children were infused with cord blood through the project during the pandemic, bringing millions of dollars through the program.
Duke had been able to secure an investigational new drug application (IND), for cord blood or stem cells related to cord blood, related to a number of research studies through the Marcus Center. As well, Dr. Kurtzberg also applied for and received three patents in 2021 for autism-related uses of stem cells, classified as “methods for the treatment of autism disorders”.
I spoke with bioethicist Leigh Turner, who shared his concerns: “The expanded access program at Duke is troubling because parents pay substantial fees for what many of them clearly believe are safe and effective stem cell treatments for autism spectrum disorder.”
In his research on crowdfunding for medical tourism, Turner, with fellow bioethicist Jeremy Snyder, discovered families crowdfunding on platforms like GoFundMe to raise funds for their travel fees associated with their child being part of the stem cell experiments. Turner describes one family reportedly trying to crowdfund $30,000 to pay for the cost of two infusions provided through the EAP. “Other crowdfunding campaigns also reveal the substantial costs associated with accessing stem cells through Duke’s expanded access program,” he told me.
“They [took] an FDA process—the EAP—that’s supposed to be used for last-hope, potentially life-saving drugs, like cancer drugs, and exploited it to bring an unregulated, implausible product to market.”
The Facebook connection
At same time Cryo-Cell and the Duke team were trumpeting their partnership, I was spending a lot of time at home, recovering from a series of cancer interventions that would continue into 2021. During my time on the sofa, I’d gotten more and more involved in parent autism groups on Facebook, beginning to do research for a book about fake autism treatments. That summer, I was able to obtain primary information and documents from parents, information that had been denied in my Freedom of Information requests to the FDA.
From viewing correspondence from Duke, which parents shared with me as attachments via Facebook Messenger or directly in parent group posts, I learned that the Duke team told parents the EAP was a “compassionate care” program.
I also found that researchers also promoted the studies through parent-based channels. For example, Dr. Kurtzberg took part in a Facebook Live interview with a Facebook group that is dedicated to exploring multiple “autism treatments” (including Cysteine-Rich Whey Protein and fecal transplants). The video was then posted on the host’s YouTube channel.
The “alternatives treatments for autism” Facebook community was a conduit for the Duke team to promote its project to parents. Meandering far from the cautious statements of her team’s clinical trials reports, Kurtzberg stated in the video for a parent-based Facebook group in July 2020: “We heard enough compelling stories [from parents] to believe them.”
“I would hope we get to a point,” Kurtzberg told the host, “where…under practice of medicine you could go to a clinic and get an infusion and have it reimbursed by insurance companies.”
All summer long, I’d been dropping information both to regulators and media, including Tom Porter at Insider and to Vice, where Anna Merlan was researching the story. In her 2020 coverage, Merlan explored how the Duke team had promised it could potentially “improve social skills and the ability to communicate with others in children with autism.”
When Vice contacted the FDA about Cryo-Cell’s claims, officials replied the agency had not approved any regenerative medicine products, including stem cell therapies, for the treatment of autism. The agency also wrote: “The only stem cell–based products that are FDA-approved for use in the US consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood.”
Meanwhile, Vice reached out to leadership at Duke, which replied with renewed hope in new studies, in the wake of their earlier trials that showed no evidence of benefit, writing to Vice: “Duke’s institutional position is that additional research is required and to encourage further study to provide definitive results.”
Past scandals and future uncertainty?
Around this time, I also connected with patient advocate Elizabeth Woeckner, who informed me that it was not the first time Kurtzberg and colleagues had run a pay-to-play clinical trial based on hope.
In the early 2000s, a team led by Kurtzberg charged 69 families of children with fatal diseases such as Tay Sachs and Sanfilippo disease more than $69 million for experimental treatments. The treatments were not proven. Journalist Diane Keough, writing for the Cleveland Plain Dealer wrote: “Many of Kurtzberg's colleagues involved with stem-cell transplants vigorously oppose the procedure for Tay-Sachs children. Some at Duke refuse to participate in the pre-procedure tests.” In 2008, Cordus/Cord:Use, a private cord-blood bank based in Florida, opened a branch at Duke. Kurtzberg received a fee for every unit of blood collected and processed for Cord:Use.
Shortly after the Plain Dealer had run the story, Cord:Use was acquired by Cryo-Cell and, 12 years later, the Tay Sachs study continued to recruit for clinical trials.
Knoepfler also observed that the project was reminiscent of another, ill-fated attempt by a university to charge for experimental stem cell access. Bioethical issues arose in 2016 when researchers at Northwestern University required trial participants to pay hundreds of thousands of dollars to participate in an autoimmune disease clinical trial testing stem cell transplants. Northwestern’s Patient Handbook for the program even included fundraising tips for patients. The university discontinued the program in 2019.
Thinking about this history (and the broad and troubling problem of university research boondoggles), I told Merlan:
“When you see a university name on a project, you think everything must be on the up-and-up. But that’s actually not a safe assumption. Money talks.”
By 2022, the launch for Cryo-Cell’s first clinic had been delayed indefinitely and most parent testimonials were removed from Cryo-Cell’s site, replaced with a more prosaic description of Dr. Kurtzberg’s work. This included the disappointing Phase 2 results of 2020, followed by a chaser of hope in a quote from Dr. Kurtzberg:
“We are cautiously optimistic about these early findings,” she said, “but need to continue to study the potential effects of cord blood infusions in children with autism who do not have intellectual disabilities.”
But how far would the Duke team be able to ride on hype and optimism?
Coming Saturday: Was there a link between the Duke project and medical tourism to unlicensed clinics for “stem cell autism therapy”?
[1] My definition of Conflict of Interest comes from the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ch 7, sec. A), which guides Canadian research and reflects the over-arching values and definitions of research ethics in the US and Canada.
[2] These high hopes were tempered by Cryo-Cell via the following disclaimer, on Slide 2:
“Statements herein the terms “believes”, “intends”, “projects”, “anticipates”, “expects”, and similar expressions as used are intended to reflect “forward-looking statements” of the Company. The information contained herein is subject to various risks, uncertainties and other factors that could cause actual results to differ materially from the results anticipated in such forward-looking statements or paragraphs, many of which are outside the control of the Company.”
[3] FDA regulations applicable to Expanded Access require that patients have a serious or immediately life-threatening disease (see 21 CFR 312.300). When patients are charged for Expanded Access, FDA must authorize the charges and the charges are limited to direct costs (21 CFR 312.8). Expanded Access may be provided on an individual patient basis, intermediate population, or widespread treatment group. (312.310, .315, .320).