A list of stuff for your weekend reading enjoyment ranging from research pubs to news to commentary.
Human neural stem cells (green) guided by electrical stimulation migrated to and colonized the subventricular zone of rats’ brains. This image was taken three weeks after stimulation. JUNFENG FENG/UC DAVIS, SACRAMENTO AND REN JI HOSPITAL, SHANGHAI
FDA new post on its plans for guidance docs in 2017. Hmm, what does the part on tissue and advanced therapies relevant to stem cells mean exactly? Is no mention of the four draft guidances from past years related to stem cells and regenerative medicine a bad sign? Who knows?
And as a bonus, a very old, somewhat wacky and in-your-face post of mine on “Dr. No” and peer review of science manuscripts and grants. I still hate your paper….
University of Minnesota bioethicist Leigh Turner has been threatened with a lawsuit by a stem cell clinic-related business. Threats in this arena come up every so often and as much as they are unpleasant realities, they can also reveal some important aspects of the stem cell arena. Ars Technica reported yesterday that Leigh’s recent paper on stem cell clinics and businesses associated with them with listings of non-FDA approved offerings in Clinicaltrials.gov was the impetus for the threat of a lawsuit and intention of asking for a retraction/correction.
An email to Leigh from Duncan Ross, the president of The Kimera Society (one of several organizations discussed in Leigh’s paper), included the reported litigation threat, which was quoted in Ars this way:
“I encourage you to amend your publication or I am going to bring suit against the institution for defamation or slander. I am going to lobby the journal for the retraction of this publication. I followed the letter of the FDA as it exists at this time and I am not going to have my name disparaged because of your lack of interest in due diligence…You continue to assume I’m being devious in some way and I’ve had enough.”
As someone who not only does stem cell research, but also writes about stem cell research and clinics, this struck me as an important development and I wanted to learn more about it. I asked Leigh for comment on this situation and he sent me his perspective along with his view of the larger context (you can read his full comment here):
“My article accurately states that the Kimera Society registered on ClinicalTrials.gov a pay-to-participate study in which adipose derived stem cells are administered to individuals with Chronic Obstructive Pulmonary Disease. The ClinicalTrials.gov listing does not disclose that study subjects are charged but this information is in the public domain and Duncan Ross, founder of Kimera, acknowledges that study subjects with COPD pay to participate in this study. My article also argues that studies involving administration of autologous adipose-derived stem cells to individuals with COPD appear to require an Investigational New Drug application that has been submitted to the FDA for review and cleared by CBER. In response, Duncan Ross has called for a retraction of my article and threatened that he will sue for libel or defamation if the article is not corrected or retracted.”
For balance I also asked Duncan Ross for a comment on this situation. I thought this was particularly important to do since Leigh and I have published work together, and share some concerns about direct-to-consumer marketing of stem cells. Here’s the comment that Ross emailed me for this piece:
Duncan Ross, Kimera Society
“My issue with Dr. Turner’s approach is this. Even in the case of your one page blog post, you chose to reach out to me to understand what I, personally, hoped to achieve and/or had done to support the publication of the trial. In fact, I had received IRB approval, whereas Dr. Leigh insinuates throughout his publication that no IRB approval is needed for publication on clinicaltrials.gov. By writing these types of sensational articles, without due diligence, he piques the interest of journalists. These journalists write an article based on a DRAFT guidance, not fully understanding what that means. Then in an email back and forth that I have limited time to attend to, I send only the 2015 approval. That get’s printed. In fact I renewed the IRB every year but didn’t care to continue my discussion with Leigh. What you end up with is someone with a non-scientific background, taking all his time to research and call out companies by name, making them look illegal when in fact I have been in contact with the FDA and done what they require AT THIS TIME. I stood up at the scientific meeting, not public, and suggested that there should be some mechanism to regulate stem cell clinics. There is none at this time. I would pursue it myself through my non-profit. SO failing a pathway, and if IRB approval is not good enough for Leigh, he is going to continue to run around half-cocked and telling half truths. If someone, and I suppose it is going to be me, does not highlight his wholly negative approach, then we might end up curtailing the positive clinical outcomes that the pharmaceutical industry is taking note of and working towards. In fact, my research and the direction of my company is wholly focused on exosome therapies now, a discovery that came out of my experience with these types of autologous stem cell therapies.
If you would like a big red box that says “paid trial’ on clinicaltrials.gov then lobby for its inclusion. If you would prefer stem cell clinics NOT get IRB approval, which I doubt you do, then state that to. I don’t see how choosing the only groups actually working through the requirements available to fulfill today is helpful or professional. Why not discuss the warning letters that were issued and how they were based in large part on sterility.”
Overall, there are hundreds of clinics and associated businesses marketing fat stem cell and other kinds of stem cell treatments for any of a whole medical encyclopedia worth of health conditions. Leigh and I reported on this in our paper in Cell Stem Cell last year. In my opinion, Leigh’s overall scholarship in this area is meritorious and has unique, positive impact. Even so, writing about stem cell direct-to-consumer businesses in any form whether it’s an academic paper or blog can be dicey.
In his comment to me, Leigh highlighted the possible impact that litigation threats can have:
“Mr. Ross’ threat is all-too-representative of the responses that emerge from individuals associated with businesses that charge patients for unproven stem cell interventions. When critiqued, they have a habit of attempting to threaten critics and intimidate them into silence. Such threats have a chilling effect on scholarship. In particular, they make academic journals and researchers wary of identifying businesses by name and critiquing specific commercial practices. The threat of litigation has impeded the ability of researchers to conduct research on such business and publish articles that address important ethical, legal, and scientific issues associated with their marketing claims, business practices, and clinical activities.”
However, one of the challenges for potential plaintiffs in such situations is that just the filing or even threat of a suit poses the risk of bringing them a hefty amount of often negative media attention a la “The Streisand Effect”.
Beyond the potential litigation issue, the Ars piece provides helpful background and new quotes from various parties including stem cell clinic leadership. One of the other interesting aspects of the Ars piece was that it got a meatier FDA quote on stem cell clinics than pretty much anything else I’ve seen from the agency in the recent past:
“We recognize that there are a number of clinics operating, which do not register with FDA. Consumers are encouraged to contact FDA and the appropriate state authorities in their jurisdictions to report any potentially illegal or harmful activity related to stem cell based products. We also encourage patients and health care providers to report adverse events associated with cellular therapies to FDA.”
Does this mean the FDA soon will actually do something concrete to bring more clarity and order to the stem cell commercial arena?
I doubt it, at least most likely not any time soon. We’ll see if as indicated in the new FDA Commissioner’s blog post the upcoming policy statements from the agency in September and then in later months might clarify the regulatory path forward for stem cell offerings such as adipose stem cells as well as other big issues such as non-homologous use and minimal manipulation. One of the rare areas of relatively greater agreement amongst many of the various stakeholders involved in or discussing stem cell clinic practices is the desire for more clarity and consistency from the FDA.
Will Kimera follow through and actually file suit against the University of Minnesota or Turner? If history is any guide, such threats almost always do not result in an actual lawsuit, but it’s possible. Regardless, I’d ask you readers a couple more questions: what is this situation telling us about the stem cell commercial arena today, and what risks and considerations are involved in being a public critic of specific commercial or other practices in the life sciences?
It’s definitely not for the faint of heart.
Note: This piece has been updated since its original posting with a few edits to reflect new information that arose in the comment thread including from Kimera’s Duncan Ross that Kimera may be more of a stem cell clinic-associated business (e.g. supplying cells to clinics) rather than a clinic itself.
The five total named patients involved in the suit include four new ones Alexandra Gardner of Colorado, Stephen Ginsberg of California, Jennifer Brewer of Montana, and Rebecca King of Arkansas, and then the original plaintiff Selena Moorer, who is a resident of Florida. Reportedly each StemGenex customer paid $14,900 for their stem cell transplant.
Notably, four of the patients mentioned in the document traveled from other states to the San Diego area to receive stem cells from StemGenex. This seems to be a more general thing with the business and its customers as the amended complaint document quoted the StemGenex website that, “over 70% of patients travel to StemGenex Medical Group from out of state.”
Besides the business itself, the Defendants listed include the following: “ANDRE P. LALLANDE, D.O., SCOTT SESSIONS, M.D., RITA ALEXANDER, and DOES 1-100.” The LA Times recently reported that Sessions was the subject of California State Medical Board action. I think that he is no longer associated with StemGenex. For other archived posts on StemGenex see here. The new court document indicates that the health conditions of the plaintiffs for which they thought stem cells might help include lupus, diabetes, painful spine and joint condition, and Multiple Sclerosis (MS).
More broadly businesses marketing non-FDA approved stem cells to patients claim that stem cells can help a whole array of health problems. In my opinion it is highly unlikely that one or even two types of stem cells could be a safe and effective way to treat so many conditions. The data just isn’t there from properly controlled studies.
The suit against StemGenex makes specific allegations about the clinic’s marketing and practices. The first 3 parts of the action described in the new document provide some sense of the specific major allegations:
“1. This is a class action against STEMGENEX MEDICAL GROUP, INC., and related persons and entities (collectively, “Defendants” or “StemGenex”). This action arises out of StemGenex’s scheme to wrongfully market and sell “stem cell treatments” at their La Jolla, California location to consumers nationwide.
2. StemGenex’s consumers are often sick or disabled, suffering from incurable diseases and a dearth of hope. StemGenex’s marketing makes claims to these consumers that by performing liposuction of a person’s 4dukt fat cells, processing them, and injecting them back into a person as stem cells (the “Stem Cell Treatments”), they effectively treat a multitude of diseases.
3. StemGenex claims that 100% of its prior consumers are satisfied with its service. StemGenex has no reasonable basis to make the claim it has made about 100% consumer satisfaction. StemGenex omits material information from all marketing about the Stem Cell Treatments and the dissatisfaction and complaints of ineffectiveness from people who have purchased the treatments.”
The case remains open and to my knowledge its class status is not yet approved. The specific allegations also have not been addressed in court as to their veracity. The case could be dismissed, it could proceed as a class suit or move forward but not as a class suit, or it could be settled.
The FDA took some big action last week and issued a major statement today on stem cell clinics (see my post here). I asked Dr. Mark Berman of the Cell Surgical Network if he had any statement regarding the recent action and statement from the FDA today that involved flagship network member clinic, California Stem Cell Treatment Centers.
Dr. Berman sent me the new press release from Cell Surgical Network, which you can read here.
Amongst other things, the Cell Surgical Network PR makes some strong statements that I’ve got as bullet points below:
The PR defended the work with StemImmune, which it said involved many top doctors.
The PR said that the Department of Defense was involved.
The PR said there was no charge to patients for participation in this particular interventional work. I’d be curious how it was funded then.
It mentioned “multiple IDE and IND applications” having been submitted, which is notable. What is the status of these at the FDA? Wouldn’t the work with StemImmune require pre-approval from the FDA in the form of an IND (not just submitted, but favorably reviewed by the FDA), BLA, and more before experimenting on patients? In my view, it sure seems that way.
The PR singled out FDA Commissioner Gottlieb, saying, “His comments show a lack of understanding surrounding autologous surgical procedures.” Really? That’s an aggressive statement in my opinion.
It said regarding Cell Surgical Network interaction with the FDA inspectors, “After sharing with and educating the inspectors as much as we did…”
In short, Cell Surgical Network is responding vigorously to the FDA with this PR.
Sacramento’s Nervana stem cell clinic has been selling non-FDA approved stem cell therapies to patients for a variety of conditions including arthritis, pain, and neuropathy for a while now since last year, but in my opinion there isn’t good evidence to back up using amniotic or fat stem cells for such conditions. Further, my understanding is that if living amniotic stem cells are being used in this way, they would constitute a biological drug requiring FDA pre-approval. Nervana’s advertising is part of a larger trendof stem cell clinics paying for mainstream media ads to broaden their customer base.
Still, for a while there we in this community saw many ads for Nervana in our local paper the Sac Bee and some patients told me they had gone to the clinic. Others were interested in learning more. Overall, I view the kind of stem cell offering being sold at such clinics as at best a risky experiment. So how have patients who paid $5,000 to Nervana felt their ‘treatments’ turned out? It’s hard to be sure, but one place that we are increasingly seeing such isu on clinics pop up is on Yelp and other on-line review sites.
For Nervana, the Yelp reviewsso far may be giving some indigestion. While there are only 4 reviews so far and that’s a very limited sample, the average rating is 2 out of 5 stars and it would be an average of 1 star, but for the single 5-star review.
The 3 out of 4 Nervana Stem Cell customers who gave it one star are specific about their reasons why. One reviewer Barbara says, “the treatment was a failure”, she never saw the doctor there, and she indicates that she believes further testing would have shown that she wasn’t a good candidate for the stem cell therapy to begin with. She mentions she wouldn’t mind a refund.
Another reviewer SR also has some negative words for Nervana Stem Cell and pointed out as well that he wasn’t seen by a physician. Finally, reviewer Liz, who weighed in first, is “very suspicious” and self-reports that her husband was a customer at the clinic.
These kinds of reviews may reflect a growing ekspresi dominan where when considering a stem cell treatment or after one is received, the public view themselves as consumers and if they aren’t happy they will say so. In the past, I’ve suggested to people to at a minimum do your due diligence in advance about a possible stem cell therapy that you would do in buying a car. Ask a lot of questions, be skeptical, get other opinions, and more. See my patient guide to stem cell treatmentsand talk to your primary care doctor. When in doubt, don’t do it.
California now has a first-of-its-kind stem cell law that requires clinics pitching non-FDA approved stem cell offerings to be upfront with patients. It’s a bill that will help to protect patients. How?
With Jerry Brown’s signature yesterday, the new California law mandates that stem cell clinics in our state take some steps to inform patients of various facts regarding what the clinics are marketing.
The bill, SB 512, was sponsored by Senator Dr. Ed Hernandez and now as a law adds Section 684 to the Business and Professions Code, relating to healing arts.
In the press release, Hernandez described the new law:
“I authored SB 512 to establish protections for consumers seeking early-stage, unproven experimental therapies,” said Senator Hernandez. “There are currently over 100 medical offices in California providing non-FDA approved stem cell treatments. Patients spend thousands of dollars on these treatments, but are totally unaware of potential risks and dangerous side effects. Thank you to Governor Brown for understanding the need for this law.”
The digest of the bill (now law) begins this way:
“This bill would require a licensed health care practitioner who performs a stem cell therapy that is not approved by the United States Food and Drug Administration (FDA) to communicate to his or her patient seeking stem cell therapy specified information regarding the provision of stem cell therapies on a specified notice in a prominent display in an area visible to patients in his or her office, posted conspicuously in the entrance of his or her office, and provided in writing to the patient prior to providing the initial stem cell therapy.”
The law requires this specific notification by the clinics:
“THIS NOTICE MUST BE PROVIDED TO YOU UNDER CALIFORNIA LAW. This health care practitioner performs one or more stem cell therapies that have not yet been approved by the United States Food and Drug Administration. You are encouraged to consult with your primary care physician prior to undergoing a stem cell therapy.”
This notice must be posted in the clinic and given in writing to the patients. The law also has some teeth to promote compliance. After the first violation, each subsequent violation results in a $1,000 fine.
Big kudos to Senator Hernandez and CCST Senate Fellow, Bao-Ngoc Nguyen, who made this possible through a lot of hard work. I was happy to have some tiny role in helping, including testifying at the Capitol here in Sacramento in support.
One of the most important sections gets the California State Medical Board involved:
“(e) The Medical Board of California shall indicate in its annual report, commencing with the 2018–19 annual report, all of the following with regard to licensees who provide stem cell therapies:
(1) The number of complaints received.
(2) Any disciplinary actions taken.
(3) Any administrative actions taken.”
Taken together, the provisions of this law will help consumers learn more about the stem cell clinic industry, make better decisions about their health and that of their loved ones, and delineate the difference between stem cell clinics versus compliant researchers conducting stem cell clinical trials with FDA approval.
In the big picture, this new California law plus a more active FDAon the stem cell front together give me more hope that the wild west of stem cell clinics can be reined in sooner rather than later! Perhaps other states will follow suit with new laws and state medical boards will get more involved in overseeing stem cell therapies. With more 570 stem cell clinics in the US and more than 100 here in California alone, more efforts like these are needed on the consumer protection and educational outreach front.
What does the wide stem cell and regenerative medicine community think of California’s new stem cell law requiring that clinics selling non-FDA approved stem cell offerings make specific disclosures to prospective customers and that the state medical board keep track of how this all unfolds?
You probably already know that I am supportive of the California law. With more than 100 clinics in California as of last year marketing non-FDA approved “treatments” and this number apparently increasing, something needs to be done to protect patients. You can see the 2016 map of just the S. California clinics at right from Leigh Turner and my Cell Stem Cell paper last year.
Notably, Texas also has a stem cell law, but one that is not ideal overall and tends toward promoting stem cell businesses relatively more than protecting patients. Due to the efforts of some stem cell advocates in that state, the Texas is not nearly as bad as it started out.
Below I’ve listed some of the reactions I’ve seen ranging from stem cell scientists to policy makers to clinics themselves.
From stem cell scientist Jeanne Loring:
“This is a really good start to educating people that the FDA is working to approve safe effective stem cell therapies, and warning people that the unapproved clinics only care about money, not people’s health.”
From the Sacramento Business Journal, stem cell scientist and former President of ISSCR Sean Morrison supports the new stem cell law, but emphasizes as well that more needs to be done:
“The new law is “one small step in the right direction (to ensure) consumers are informed,” he added, but it will be important for the FDA and state agencies to remain vigilant against unscrupulous stem cell clinics. Morrison suggests that one reason the number of clinics increased in the first place is because the FDA was too lax in its oversight.”
I agree that more needs to be done, but sometimes progress is in steps.
And from the same article, the operator of the Nervana stem cell clinic here in the Sacramento area (see my past posts on it here) also says he supports it:
“Locally, Dr. Tushar Goradia, president of Nervana Stem Cell Center in Fair Oaks, said he supported the law. “I am in favor of it and anything that improves patient awareness and informs consent,” he said.”
I’d be curious if Dr. Goradia believes the law applies to Nervana or not, which seems to predominantly sell non-FDA approved amniotic stem cell therapies.
Some amniotic stem cell clinics have argued that they are exempt from FDA oversight, but an important issue is whether such firms are using living cells (and if so, are these really “stem cells”?), as they most often seem to be marketing, or just dead extracts of amniotic membranes. In either case, could the products still be considered drugs because of non-homologous use (e.g. injection into a knee joint, as joints have no homology to amniotic membrane).
A bit of other coverage out there so far including from David Jensen and RAPS.
The FDA took some big action last week and issued a major statement today on stem cell clinics (
California now has a first-of-its-kind 
What does the wide stem cell and regenerative medicine community think of