stem cell clinic

Naturopaths and quack stem cell clinics revisited

oracknows — Mon, 11 Sep 2017 01:26:58 +0000

Naturopaths and quack stem cell clinics revisited

A week ago, I wrote about a naturopath in Utah named Harry Adelson, who was advertising his use stem cells to treat lumbar and cervical disk problems, including degenerated and dehydrated disks. That alone was bad enough, but what elevated "Not-a-Dr." (my preferred translation of the "ND" that naturopaths like to use after their names to confuse patients because it's so close to "MD") Adelson above and beyond the usual naturopathic quackery is his cosplay of an interventional radiologist, in which he purchased a C-arm to use fluoroscopy to inject his "stem cells" right into the intervertebral disks of patients. In the meantime, I also reiterated just how much damage naturopaths do when they try to treat real diseases like cancer and how sensitive they are to having their quackery called out.

Getting back to naturopaths using what they claim to be "stem cell therapy," Not-a-Dr. Adelson is not alone among naturopaths in opening clinics devoted to isolating who knows what kind of cells from patients' bone marrow and/or adipose tissue and injecting them who knows were without any good evidence that they actually do anything. Sadly, they are like a lot of MDs in "regenerative medicine," only even less concerned about science. Indeed, I soon discovered that there are quite a few naturopaths out there offering prolotherapy and a variety of stem cell therapies, just like unethical MDs do. All I had to do was to Google "stem cells" and "naturopathy" to find a number of examples. For instance, the Stem Cell Rejuvenation Center in Phoenix is run by Not-a-Drs. Timothy Pierce, Jaime Ewald, and Julie Keiffer, who claim to be able to use stem cells derived from adipose tissue or isolated from bone marrow to treat autism, amyotrophic lateral sclerosis (Lou Gehrig's disease), cerebral palsy, degenerative disc disease, heart disease, muscular dystrophy, Parkinson's disease, stroke, spinal cord injuries, and, of course, erectile dysfunction, all for the low, low price of $7,100 for either adipose or bone marrow-derived stem cell treatments or the deal of $9,600 for both. What a bargain for something that hasn't been shown to work in clinical trials! And how on earth are naturopaths allowed to do bone marrow biopsies and liposuction to gather the marrow and adipose tissue, respectively upon which to work their woo? Well, in Arizona, minor surgery is within the scope of practice of naturopaths.

Elsewhere in Arizona, East Valley Naturopathic Doctors also offer "stem cell therapy":

This incredible advancement in natural healing means that stem cells can be harvested from a patient’s fatty tissue and reintroduced into that patient’s body. These stem cells have the ability to travel to areas of the body that have damaged tissues. The stem cells can then either instigate healing or actually transform into the type of cells needed to repair an injured area. The possible benefits of this kind of treatment are staggering!

Because the FDA has yet to approve this therapy, it cannot be said that stem cells are used specifically for the treatment of any disease. However, empirical evidence shows that this therapy is beneficial to people who suffer from many different illnesses, such as:

Neurological diseases

Chronic joint pain

Autoimmune conditions

Heart disease

Pulmonary issues

How nice. It's basically a quack Miranda warning for their stem cell facility, Global Health Stem Cell & IV Therapy, run by two of the naturopaths there, Not-a-Dr. Jason Porter and Not-a-Dr. Julie Keiffer. Wait, didn't I just say that Keiffer works at the Stem Cell Rejuvenation Center, too? Wow. More cosplaying of real doctors, she must work at two different practices and out of two different stem cell centers. The ones listed on her website include East Valley Naturopathic Doctors, Valley Medical Weight Loss, and Peace Wellness Center, which appear to be where she sees patients. On her website, she advertises using platelet-rich plasma for the following purposes:

For Hair loss and hair thinning, PRP is injected into the scalp to stimulate the hair follicle strength. In addition to injections, Micropen™ with PRP topically assists with the stimulation of the hair follicle.

For sexual enhancement, the O-Shot® procedure for women and the Priapus Shot ® procedure for men, delivers PRP into the genitalia which may enhance sensitivity, strength and possibly size for men. For more detailed information refer to Patient Resources for links to desired sites.

Oh goody.

I could go on, but you get the idea. I've found naturopaths offering dubious stem cell therapies in Canada, Germany, California, Oregon, and all over. It's apparently becoming such a thing that actual MDs running dubious stem cell clinics are feeling threatened. For instance, here is Dr. Chris Centeno asking, "Should you let a naturopath stick a needle in your spine?" His answer is no, for many reasons that are correct:

Much has been made by naturopaths that their training is now equivalent to that of an MD or DO physician. However, some of the issues that came up in the recent board discussion were reports of naturopaths missing common medical side effects of spinal injections, like a dural leak. In fact, naturopaths were not even able to understand that this was a possible complication of the spinal injection procedure they performed. So how is it possible with all of the hours that naturopaths claim they train that they’re not able to conceptualize or catch a simple and common complication of spinal injection? The reason is contained in a simple statement made by one of our fellows.

A few weeks ago, we had a patient who needed to be checked for a postprocedure infection. I couldn’t see the patient, so I had one of our two fellows check him out. While all of the data looked like the patient didn’t have an infection, what the fellow told me verbally was important. He said that the patient “didn’t look toxic.” What the fellow meant was that after training in a large university medical center where he saw many patients who were infected and toxic, or “sick,” and many who were not, he was using that experience filtered through the large neural network in his head to rule out a pattern of patient characteristics that he had associated with patients who were sick, or toxic. These may be the paleness of the skin, a glassy look in their eyes, how they interact, and so on. Every MD or DO who trained in a large university medical center knows what that fellow meant. The issue with naturopaths, chiropractors, and acupuncturists is that they don’t train in these settings. So when they learn how to perform procedures that may injure patients and make them “toxic,” they have no way of knowing, despite many weekend courses, how a sick patient presents. Why? Most of their training is on well patients with chronic problems, like pain or irritable bowel disease or allergies, not on ill patients undergoing surgery in the hospital.

It's true. One of the most important skills we as physicians learn is how to recognize when a patient "looks sick," and by "looks sick" I mean sick enough that he's about to take a significant turn for the worse if something isn't done very soon. It's very much a skill that involves pattern recognition. It's hard to explain in words how to do it. I can list some of the characteristics we physicians look for, as Dr. Centeno did above, but in practice it's more of a gestalt, the recognition of several observations together that tell you the patient is doing poorly. As I point out, medicine should be based in science, but there are still skills in pattern recognition that are part of the art of medicine. Perhaps one day AI will be able to replicate the ability of an experienced clinician to recognize this constellation of observations that tell us that a patient, even one who might not appear that sick at the moment to an untrained observer, is about to get a lot sicker soon. This skill can't be learned quickly. It takes seeing a lot of patients, ranging from not-so-sick, to teetering on the brink, to having fallen over the cliff into life-threatening decompensation, and naturopaths simply do not see enough sick enough patients to develop that skill. (In fairness, some physician specialties never do, either, and I sometimes worry that it's been so long since I did general surgery that my skills in that area might have become rusty.)

Of course, Dr. Centeno is doing the very same thing naturopaths are doing; so, even as I agreed with everything he said about naturopaths and more, it was hard for me not to get the impression as I read his article that that he was far more about protecting his turf than he was about actually protecting patients. (If that weren't the case, Dr. Centeno wouldn't be selling expensive and unproven stem cell therapies for indications for which they remain largely untested and unproven, would he? He'd be doing real clinical trials to determine if they work, instead of what he is doing now.) Reading his op-ed, I have little doubt that he views these naturopaths offering stem cell therapies more as a threat to his business model, as competitors muscling in on his action, endangering his profits. Even as I agreed with what he wrote about naturopaths, I couldn't help but think that he's no better and in fact might be worse than the naturopaths doing stem cell therapy. After all, he has the training to know better, but apparently does not (or chooses not to). He's decided to forego all that pesky rigorous science and, instead of doing proper clinical trials, to forge right ahead selling his treatments using patient registry data and anecdotes. In this, he has a lot in common with the naturopaths he denigrates.

Indeed, when it comes to stem cells, I fear that we as MDs are teaching naturopaths our worst habits. For instance, look at the excuses made by this stem cell quack named Dr. Mark Berman, complete with a quack Miranda warning about his treatments, for charging big bucks to patients for what he openly admits are unproven therapies:

But a website for his Cell Surgical Network, an umbrella for dozens of stem cell clinics nationwide, lists more than two dozen other conditions the physicians are “currently studying,” including Parkinson’s, amyotrophic lateral sclerosis — more commonly called Lou Gehrig’s disease — congestive heart failure, lung disease, glaucoma, and muscular dystrophy.

The website is careful not to promise that the stem cell injections can cure or treat those diseases, and Berman said he makes it clear to all patients that the work is investigative and not FDA-approved.

Berman acknowledges that he has no published studies to back up his treatment. But he says he’s certain it works and is safe. As proof of his confidence, he notes that he used the therapy to successfully treat his wife for hip pain.

He says critics, including pharmaceutical companies and academics, want to profit by patenting stem cells and fear “disruptive technologies” that come from entrepreneurs rather than from their own incremental research.

I'd say that it's more like Dr. Berman not wanting to wait for that "incremental research" to determine whether the treatments he is providing patients actually work and are safe. He basically admits that he has no evidence other than his certainty that "it works and is safe." That's just not good enough, particularly if you're charging patients close to $9,000 a pop. I consider that to be unbelievably unethical, whether it's a naturopath doing it or an MD like Dr. Berman. They both claim to do tests to demonstrate that stem cells are present, but, absent their publishing their protocols, there's no way of knowing if they actually know what they're doing. I highly doubt they do.

In the end, naturopaths go where the ducks are, but, even more than that, they go where the quacking is the loudest. It doesn't matter if it's really "natural" or not. After all, in functional medicine what is "natural" about doing batteries of blood tests for dozens of hormones, nutrients, and other factors and then providing supplements and intravenous therapies to "correct" them all? What is "natural" about extracting fat and doing all sorts of manipulations to isolate individual cell types or doing bone marrow biopsies and isolating the stem cells, then reinjecting them? Of course, then there's the issue of whether what is being injected are really "stem cells" at all, which in many cases is highly doubtful given the lack of rigorous descriptions of the protocols used to isolate the stem cells. Stem cell clinics have become a profit train for unethical real doctors. Given that naturopaths are quacks who cosplay real doctors, it's not surprising that they'd cosplay the unethical ones too and jump on the gravy train.

oracknows Sun, 09/10/2017 - 21:26

What's scarier than dubious stem cell clinics? A naturopathic stem cell clinic!

oracknows — Fri, 01 Sep 2017 05:00:07 +0000

What's scarier than dubious stem cell clinics? A naturopathic stem cell clinic!

I've frequently written about bogus stem cell clinics that use hard sell techniques to sell unproven and expensive "stem cell treatments" to desperate patients. For instance, I deconstructed the story claiming that hockey great Gordie Howe improved so markedly after a severe stroke, thanks to stem cells offered to him for free (because of his celebrity) by a dubious stem cell company (Stemedica) through its Mexican partner (Clínica Santa Clarita). The whole incident basically opened my eyes to just how unethical the for-profit stem cell clinic industry is, as clinics use hard sell techniques more akin to used car salesmen to peddle potentially dangerous therapies even right here in the good ol' USA. The level of corruption and lack of ethics are truly astounding. Indeed, some stem cell clinics have followed the Stanislaw Burzynski model in getting patients to pay to be on dubious clinical trials that are designed primarily to sell product rather than to answer any sort of scientifically important question.

The problem, of course, is that very few stem cell therapies have compelling evidence for efficacy and safety. Yet that doesn't stop dubious stem cell clinics all over the country from selling treatments claiming to improve or cure everything from heart disease to lung disease to cancer to even autism, all with minimal evidence that what these clinics are doing can do anything of the sort. That's why I view it as very much a good thing that the FDA has recently made noises about cracking down on stem cell clinics, a move that's long overdue. I hope it continues.

Regardless of whether the FDA's new loving attention to stem cell clinics is sustained or not, yesterday I learned of something very, very disturbing. Let's just put it this way: What's scarier than an unregulated, dubious stem cell clinic selling "stem cell"-related "cures" for lots of money? I'll tell you. It's an unregulated, dubious stem cell clinic selling "stem cell"-related "cures" for lots of money run by naturopaths. I kid you not. there's a clinic in Park City, Utah, the Docere Clinics, in which a naturopath is advertising stem cell therapies that it offers. The naturopath, Harry Adelson, ND (Not-a-Doctor) is described thusly:

Stem cells, specifically mesenchymal stem cells (MSCs), have been called “patient-specific drug stores for injured tissues” because of their broad range of healing abilities. MSCs are directly responsible for healing damaged tissues after injury. Upon encountering damaged tissue, they release proteins that decrease inflammation, kill invading microbes, and trigger the growth of new connective tissues and blood vessels. In the case of severe damage and cell death, MSCs have the ability to turn into healthy versions of damaged or destroyed cells that they encounter.

When we take MSCs from your own bone marrow, from your own fat, or from both, concentrate and/or isolate them, and then inject them directly into your problem area, we ‘trick’ your body into thinking that there has been a new injury without actually causing any tissue insult, and you get a second chance at healing. In the case of advanced osteoarthritis where the population of stem cells has been depleted, we are repopulating the area with stem cells, and thereby restoring the body’s natural ability to heal itself.

The only good thing I can say about this is that Docere Clinics don't claim to be able to treat spinal cord injury, autism, or cancer. Believe me, that isn't saying much. Because, quite strategically, Docere Clinics does treat all manner of musculoskeletal pain syndromes, some of which stretch the imagination as conditions that would need something like stem cell therapies. For instance, like many "regenerative medicine" stem cell clinics, Docere claims it can treat osteoarthritis and avascular necrosis. It also claims that it can treat back pain of various etiologies and bone spurs. (One wonders why on earth one would need a treatment as expensive and radical as stem cell therapy in order to treat bone spurs.) Ditto carpal tunnel syndrome, whose pathophysiology is pretty well understood and which is treated quite effectively by carpal tunnel release surgery. (I know. I've that surgery 15 years ago and it basically cured my carpal tunnel syndrome, other than a minor twinge every now and then.)

Looking at the list, I see no condition for which stem cell therapies have been shown to be efficacious or safe, but I do see conditions that are primarily ones of chronic pain, which means that they are likely to be particularly susceptible to placebo effects. Without rigorously designed randomized, placebo-controlled, double blind clinical trials, it would be very difficult to determine whether any therapy has a significant impact on these conditions. Is there any RCT data supporting what Not-a-Dr. Adelson does? Nope. None of that stops him from doing what naturopaths love to do and cosplaying a real doctor by wearing scrubs in all his videos and pictures on the clinic website:

Dr. Adelson began his training in regenerative injection therapy (prolotherapy) in 1998 while in his final year at The National College of Naturopathic Medicine, in Portland, Oregon after having been cured of a rock-climbing injury with prolotherapy. During his residency program in Integrative Medicine at the Yale/Griffin Hospital in Derby, Connecticut, he volunteered after hours in a large homeless shelter in Bridgeport, Connecticut, providing regenerative injection therapies to the medically underserved while gaining valuable experience. He opened Docere Clinics in Salt Lake City in 2002 and from day one, his practice has been 100% regenerative injection therapies for the treatment of musculoskeletal pain conditions. In 2006 he incorporated platelet rich plasma and ultrasound-guided injection into his armamentarium, in 2010, bone marrow aspirate concentrate and adipose-derived stem cellls, and in 2013, fluoroscopic-guided injection (motion X-ray).

Prolotherapy, of course, has been around a long time but lacks convincing evidence for clinical efficacy. The same can be said of platelet-rich plasma (PRP). Neither have particularly compelling evidence for utility in the conditions for which they are commonly used. It's possible that PRP might have an effect in some conditions, but there really isn't much in the way of decent evidence to show that it does.

But wait! Did you do a double take when you saw that last sentence, wherein a naturopath is using fluoroscopy to guide his injection of stem cells. Just let that sink in a moment. How on earth could he ever be qualified as a naturopathic quack to use fluoroscopy for anything? Get a load of where he injects the cells, too:

Of the fluoroscopically-guided injections that we perform, one that stands out is the injection stem cells into the intervertebral disc. Discs are structures that are rich with nerves, but are the least vascularized tissue in the body. The way discs maintain hydration is through movement; as the disc moves, hydration comes from the vertebral bodies (bones) above and below. When we lead sedentary lifestyles or suffer traumatic injuries, the discs can become ‘desiccated’, meaning dehydrated. A dry disc is an extremely painful disc. Being able to inject a dry disc with stem cells is the primary reason we became interested in fluoroscopically-guided injection.

That's right, Not-a-Dr. Adelson is injecting "stem cells" of unclear provenance into cervical discs because he thinks the stem cells will somehow un-desiccate them and turn the old, atrophied cervical disks to shiny new ones. Here he is cosplaying a real interventional radiologist:

Yes, he's injecting into cervical and lumbar disks. What could go wrong? Well, there are nerve roots nearby that could be damaged. One can damage the disks themselves. There's a reason why becoming a board-certified interventional radiologist takes as many years as becoming a surgeon does. Perhaps what's most disturbing about this is that Not-a-Dr. Adelson trained at Yale's integrative medicine program. I wonder if Steve Novella knows his school's quackademic medicine program admits naturopaths. It led me to find that the Director of the Yale Adult and Pediatric Integrative Medicine Program is a naturopath. Although the Yale/Griffith Hospital integrative medicine program appears to exist no more, in its day it did have naturopaths as residents, as evidenced by this advertisement for a talk on naturopathic approaches to pain management, given by one of the naturopath residents.

So does Not-a-Dr. Adelson have any evidence to back up his treatment? Well, he has a TEDX talk:

It's basically an anecdote about a veteran of the Iraq/Afghanistan wars named Chris who had severe chronic low back pain due to a degenerated L4/L5 disk, suffered as a result of injuries due to his bad luck of being too close to two two different IED explosions. Apparently this veteran came to him asking him to inject stem cells into his disc. At about the 1:20 mark, you see how Adelson justifies his unethical actions. He basically portrays the options, but paints the ethical option (not using stem cells) in the worst possible light, as abandoning the patient. He portrays the other best option, enrolling the patient on a clinical trial, in an equally bad light, dismissing it saying that, well, you know, you have to be aware that you might bet a placebo. The next option he jokes about, namely taking the patient to "my offshore stem cell clinic" to treat him. Then, he portrays what he did, using an unproven technique that hasn't been validated scientifically or in clinical trials on a single patient, as the best option, the heroic option, the "can do" option. He even brags about how doing an autologous stem cell transplant is no different than doing a hair transplant. He also justifies his action by his own "conversion experience" using prolotherapy to treat his shoulder injury from rock climbing. I also learned the name of the surgeon who taught him how to do injections. Not surprisingly, it was a doctor, an orthopedic surgeon, who runs a dubious stem cell clinic in Florida.

Not-a-Dr. Adelson makes the claim that the outcomes were "so much better" than PRP that stem cell treatments "instantly became 100% of my practice," bragging about how he traveled to various Central and South American stem cell clinics. One man he mentioned was Carlos Cecilio Bratt, MD, who, it turns out, runs a stem cell clinic in Venezuela, and runs what sounds like an assembly line doing stem cell treatments. (One wonders why he hasn't published his results.) He also went to the infamous Stem Cell Institute in Panama City. He also went to Ecuador. Finally, he found MDs and DOs willing to teach him how to use a C-arm and do fluoroscopy. Naturally, Adelson finished his story by bragging about how much Chris claims his pain has improved and how good his results are. Did he mention any clinical trials? No, of course not. He does have an unrandomized, highly dubious clinical "trial," though. Unfortunately, what he doesn't have is any mention of whether he had institutional review board (IRB) approval to do that retrospective chart review and to publish it. Worse, he doesn't have anything resembling real informed consent:

Patients presenting to Docere Clinics in Park City, Utah, between July 15, 2014, and November 15, 2014, who were deemed candidates for autologous stem cell therapy, were asked to choose between being treated with BMAC [bone marrow aspirate concentrate] or SVF/ PRP [stromal vascular fraction suspended in platelet rich plasm]. e conversation can be summarized as follows: “I can do a bone marrow aspiration and treat you with BMAC, with which I have ve years of experience and am aware of data supporting its use, or I can do a lipoaspiration and a blood draw and treat you with SVF suspended in PRP, which has the potential to provide us with a far greater yield of stem cells and, theoretically, a superior outcome. However I have little experience with it and there are very few data supporting its use.” Patients then self-selected into the BMAC or the SVF/PRP group.

Then, he changed the protocol:

During this period and during preliminary follow-up with patients, I began to notice a trend that many SVF/ PRP patients reported higher satisfaction than those in the BMAC group, but the remainder were experiencing no improvement at all. Beginning November 16, 2014, I be- gan o ering patients SVF prepared as described above but suspended in BMAC rather than PRP, hypothesizing that the combination could o er the consistency of BMAC with the augmented outcomes of SVF.

This is half-assed, "make it up as you go along" clinical research at its most dubious. Adelson then looked at his outcomes using a retrospective survey. Basically, everyone appears to have done roughly the same. Given that there wasn't a hint of a whiff of a statistical analysis or power calculation, that's basically that can be said. As for the lack of IRB involvement, Adelson appears to be taking advantage of the fact that the IRB requirement, strictly speaking, only applies to human subjects research funded by the federal government, carried out at an institution (e.g., a university) that receives federal funding, or when a clinical trial is being done as the basis to seek FDA approval. True, some states have their own laws requiring that any research inside their borders have IRB approval according to the Common Rule, but I don't know if Utah is one of them.

Not surprisingly, Adelson seems utterly oblivious to what we already know about invasive surgical procedures: There can be a significant placebo effect any time you inject anything into the spine or discs. I like to use the example of vertebroplasty for lumbar spine fractures due to osteoporosis. It's been shown convincingly in at least a couple of good randomized, placebo-controlled trials to be no better than placebo. The usage of vertebroplasty has even declined as a result, albeit not nearly as much as it should have. (Yes, doctors sometimes share something in common with not-a-doctors; the unwillingness to give up treatments that science has shown to be ineffective.) Without a good RCT, it's impossible to tell if Not-a-Dr. Adelson is getting the results he gets due to placebo effects or not. Yet he just cruises along, using an unproven therapy. Worse, who knows what Adelson is actually injecting? He's described his technique for isolating stem cells, but one thing I see lacking is any characterization of the cells to demonstrate that they are what he claims they are. I also see a lack of followup images to demonstrate that the concoctions injected into the discs have had any effect at all biologically in rehydrating and renewing them. Basically, Adelson's clinical "evidence" is a joke, and a bad one at that. Yet, Docere Clinics continue to offer the treatment, and even offer a 10% discount per patient to current patients who refer new patients. Capitalism!

But how can this be legal? Apparently, in Utah, it is. Britt Hermes contacted the Utah Division of Occupational and Professional Licensing and received this reply:

Naturopath Harry Adelson who harvests and injects stem cells (using fluoroscopy!) got the approval of Utah authorities.

This is bullshit. pic.twitter.com/c6DaYVZHJe

— Britt Marie Hermes (@NaturoDiaries) August 31, 2017

Yes, in Utah, naturopathic quacks can basically do anything, science be damned. Or so it would seem. Worse, Not-a-Dr. Adelson is not alone. There are quite a few naturopaths out there offering prolotherapy and "stem cell" therapies. Be afraid. Be very, very afraid.

oracknows Fri, 09/01/2017 - 01:00

Stem cell tourism: A problem right here in the good ol' USA

oracknows — Mon, 11 Jul 2016 01:03:49 +0000

Stem cell tourism: A problem right here in the good ol' USA

Last week, I wrote about a man named Jim Gass, a former chief legal counsel for Sylvania, who had suffered a debilitating stroke in 2009 that left him without the use of his left arm, and weak left leg. He could still walk with a cane, but was understandably desperate to try anything to be able to walk unaided and function more normally in life. Unfortunately (at least given what ultimately happened), Mr. Gass was both driven enough, credulous enough, and wealthy enough to spend $300,000 pursuing stem cell tourism in China, Mexico, and Argentina over the course of four years. The result is that he now has a tumor growing in his spinal column, as reported in The New England Journal of Medicine (NEJM) and The New York Times (NYT). Genetic analysis has demonstrated that the cells in this tumor mass did not come from Jim Gass, and the mass has left him paralyzed from the neck down, except for his right arm, incontinent, and with severe chronic back pain. Worse, although radiation temporarily stopped the tumor from growing, apparently it's growing again, and no one seems to know how to stop it. Given that the traits that make stem cells so desirable as a regenerative treatment, their plasticity and immortality (ability to divide indefinitely), are shared with cancer, scientists doing legitimate stem cell research have always feared such a complication and have therefore tried to take precautions to stop just this sort of thing from happening in clinical trials. Clearly, "stem cell tourist" clinics, which intentionally operate in countries where the regulatory environment is—shall we say?—less than rigorous are nowhere near as cautious.

At the time I wrote that article, I emphasized primarily clinics outside of the US, where shady operators locate in order to be able to operate largely unhindered by local governments. You'd think that such a thing couldn't possibly be going on in the US. You'd be wrong. About a week and a half ago, Paul Knoepfler, a stem cell scientist who maintains a blog about stem cells, teamed up with Leigh Turner to publish a paper in Cell Stem Cell estimating the number of stem cell clinics in the US. The number they came up with astonished me.

Stem cell clinics: A large and growing industry

In their article, "Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry," Turner and Knoepfler explain:

Businesses marketing putative stem cell interventions have proliferated across the U.S. This commercial activity generates a host of serious ethical, scientific, legal, regulatory, and policy concerns. Perhaps the most obvious regulatory question is whether businesses advertising nonhomologous autologous, allogeneic, "induced pluripotent," or xenogeneic "stem cell therapies" are exposing their clients to noncompliant cell-based interventions. Such practices also prompt ethical concerns about the safety and efficacy of marketed interventions, accuracy in advertising, the quality of informed consent, and the exposure of vulnerable individuals to unjustifiable risks.

Prior analyses of companies engaged in direct-to-consumer marketing of stem cell interventions have not explicitly focused on attempting to comprehensively locate and examine U.S. businesses (Lau et al., 2008, Ogbogu et al., 2013, Regenberg et al., 2009), although recent scholarship has identified some U.S. businesses engaged in such activity (Connolly et al., 2014). While such companies have attracted some scrutiny from researchers and journalists, these businesses have not yet been examined in a comprehensive manner (Perrone, 2015, Turner, 2015a). This gap in scholarship has contributed to misunderstandings that need to be corrected.

For example, health researchers, policy-makers, patient advocacy groups, and reporters often use the phrase "stem cell tourism" when addressing the subject of unapproved cell-based interventions and even in 2016 assume that U.S. citizens must travel to such destinations as China, India, Mexico, and the Caribbean if they wish to access businesses promoting stem cell procedures for a wide range of clinical indications. While travel from the U.S. to international "stem cell clinics" continues, the rhetoric of "stem cell tourism" often fails to acknowledge the hundreds of U.S. businesses engaged in direct-to-consumer advertising of stem cell interventions.

Of course, I did exactly this in my previous post, not really acknowledging this industry in the US. True, I did mention the San Diego-based company Stemedica, but I mentioned that company mainly because its business model appears to involve doing actual FDA-monitored clinical trials of its stem cell products in the US but referring any patients contacting the company who are ineligible for its US clinical trials to one of its foreign partners, particularly its affiliate right across border in Tijuana, Novastem. It was, for example, Novastem through which Gordie Howe was treated for his stroke a year and a half ago. Patients referred to Stemedica's partners, of course, pay full price for the stem cell injections, usually around $30,000 a pop.

But what about US-based businesses? Turner and Knoepfler used key words and phrases such as "stem cell treatment" and "stem cell therapy" to preliminarily identify putative stem cell businesses and then evaluated the text on the websites of these businesses to refine their analysis. As a result, they identified 351 businesses offering stem cell therapies at 570 clinics, which they listed on this map:

Stem cell clinics in the US.

They also helpfully include a link to an Excel spreadsheet listing all 570 sites, noting:

Many stem cell companies employ multiple physicians and advertise interventions available at numerous clinics. Although such businesses are widely distributed all over the county, we found that clinics tend to cluster in particular states. For example, we found 113 clinics in California, 104 in Florida, 71 in Texas, 37 in Colorado, 36 in Arizona, and 21 in New York. "Hotspot" cities including Beverly Hills (18), New York (14), San Antonio (13), Los Angeles (12), Austin (11), Scottsdale (11), and Phoenix (10) are designated with stars on the map. Some metropolitan areas, including Southern California around Los Angeles and San Diego, the South Florida region surrounding Miami, the greater Denver area, and the Dallas-Fort Worth metro region, have a relatively high number of clinics even if not all such facilities are technically in one city (Figure S1). While our analyses here do not explain why these businesses cluster in particular areas, we plan to investigate this question further. Possible factors include a relationship between number of clinics and population density, regional variations in use of "alternative" medical interventions, aging population demographics, and regulatory orientation of state medical boards and consumer protection agencies.

I'm sure population density has something to do with so many clinics in California, although one would expect more in New York and Texas if it were just population density. I also suspect that the prevalence and popularity of alternative medicine practitioners has something to do with it, since, oddly enough, I frequently see ads for stem cell clinics and articles praising stem cell therapies on websites oriented towards alternative medicine. Given how often stem cells are advertised as "anti-aging" treatments (something mentioned by Turner and Knoepfler) and the popularity of plastic surgery in California, it wouldn't surprise me if there is a correlation there as well. These are definitely things that I hope Turner and Knoepfler will look at in future investigations.

So what are these clinics selling stem cells to treat? What are the claims they make? Unfortunately, the claims of US clinics are not much, if at all, different from the claims made by many stem cell tourist clinics in other countries. Claims are made that specific diseases can be treated that are just specific enough to attract customers but vague enough not to promise too much.

Claims, claims, claims, and more claims

It has to be noted that there is not just one kind of stem cell. As I described last time, they range from embryonic stem cells that require human embryos to isolate, to adult stem cells, to cells induced to be stem cells by the introduction of genes responsible for maintaining the "stem cell" state. As I'll discuss later, this matters when it comes to asking just what the heck the FDA is or isn't doing about this proliferation of stem cell businesses.

Turner and Knoepfler note that most of the businesses that they identified market autologous stem cell-based interventions; i.e., stem cells isolated from the patient and then reinfused. Most isolated these stem cells (or claimed to isolate them, given that it's not always clear how such clinics verify that what they have isolated are indeed autologous stem cells) from adipose tissue (fat) or from the bone marrow. Be that as it may, 61% of the clinics examined market autologous adipose-derived stem cell-based interventions; 48% what they describe as autologous stem cells obtained from bone marrow; and 4% stem cells reportedly isolated from peripheral blood. Not surprisingly, lots of clinics offer stem cells isolated from more than one source. Some offer "mixed" stem cells from both bone marrow and adipose tissue as "combination stem cell therapy."

About one in five clinics advertised allogeneic stem cell treatments; i.e., stem cells from another person or source. The usual sources of these "stem cells" are advertised as amniotic material/fluid (17%), placenta (3.4%), and umbilical cords (0.6%). It's noted in the report the precise source for these products was not clear in all cases, in particular for amniotic stem cells. Indeed, one wonders (at least I do) what the source of amniotic fluid is from which these clinics claim to isolate stem cells. Do they have a deal with a local obstetrical clinic or hospital to provide amniotic fluid or membranes? Do they buy placentas and amniotic membranes from a hospital? Where do these clinics get the raw material (i.e., the human tissue and fluids) to generate these stem cells from? Inquiring minds want to know!

Turner and Knoepfler also noted one business that offers what it claims to be induced pluripotent stem cells. (Remember, these are cells genetically manipulated to revert to being stem cells.) I went back to the spreadsheet and found which company offered this, Regenerative Medical Group. RMG claims to provide "induced pluri-potent stem cells from your own cells via an affiliated laboratory," but what I found more interesting were the diseases and conditions it claims to treat with stem cells. Not surprisingly, as was the case for most of the clinics listed, many of the indications were orthopedic, to regenerate cartilage and repair injury. However, RMG also claims to be able to treat kidney diseases, macular degeneration, Parkinson's disease, and, yes, autism. Under a tagline of An autism therapy that WORKS, there's even a video on the website that makes claims that can only be described as grandiose and not supported by science featuring Bryn J. Henderson, DO, JD, FACPE, CIME, the executive director of RMG:

In the video, Dr. Henderson claims that RMG has helped "dozens" of children with autism using stem cells. He claims that the stem cells circulate through the body, cross the blood-brain barrier and "make new cells" that change the course and prognosis of the patient with autism. He even claims that most of the time, the change is major. How does he know? He brags about the thank you cards he's gotten from parents. I mean, seriously. This is utterly pathetic. Even antivaccine quacks like Mark and David Geier or Andrew Wakefield can do better at providing "evidence". Note that that is not a compliment, given how poor their attempts at studies invariably are. Dr. Henderson, however, presents no science, no clinical trials, no preclinical trials, no nothing other than testimonials, although he does use a lot of science-y-sounding terms. Hell, I've seen homeopaths who provide more evidence and a more convincing presentation. At least they will cite actual patients rather than thank you notes from patients' families. (Oh, and Dr. Henderson, don't bother taking your video down; I've downloaded it.)

RMG's fact sheet on autism is no better. Citing no evidence, not even case reports, the sheet claims that stem cell infusions for autism can improve:

Social interaction
Sensory problems
Seizures
Mental health issues
Mental impairment
Digestive issues
Sleep disturbances
Aggression

What evidence is presented? Again, none. This might as well be a chelation therapy clinic. The treatment, however, takes three days, and the patient doesn't have to come back to an RMG clinic at all, although, the fact sheet hastens to add, they can undergo repeat treatments if necessary. In other words, stem cells appear to have been added to the armamentarium of "autism biomed" quackery.

I could go on, but to me stem cells for autism is so obviously dubious at best and bogus at worst that, given my interest in vaccines and the antivaccine movement's mistaken belief that vaccines cause autism, I hope you'll forgive me if I zeroed right in on autism. Indeed, nine of the clinics listed in the spreadsheet claim to be able to use stem cells of one kind or another to treat autism.

But, wait, there's more. In addition to RMG:

Another business markets access to what it describes as "embryonic stem cell" interventions. In addition, we identified two clinics that marketed "bovine amniotic cells," a xenogeneic product, for use in humans. Approximately 3% of businesses marketed stem cell interventions without mentioning a particular type of stem cells.

Perusing the list of clinics, I found it hard not to come to the conclusion that there isn't a single disease or condition that someone, somewhere, isn't claiming can be helped with stem cells of one kind or another. Diabetes, heart disease, degenerative diseases, Parkinson's disease, Alzheimer's disease, spinal cord injuries, stroke, aging, and even cancer show up on the list of conditions that these 570 clinics claim to be able to treat with stem cells, as Turner and Knoepfler note:

U.S. businesses promoting stem cell interventions claim to treat a wide range of diseases and injuries, as well as advertising stem cells for cosmetic applications, "anti-aging," and other purposes (Figure 2B). Some clinics occupy relatively specialized marketplace niches. For example, many cosmetic surgery clinics advertise such procedures as "stem cell facelifts" and "stem cell breast augmentation" as well as sexual enhancement procedures. Orthopedic and sports medicine clinics often promote stem cell interventions for joints and soft tissue injuries. Other clinics take a much broader approach and list stem cell interventions for 30 or more diseases and injuries. Such businesses commonly market treatments for neurological disorders and other degenerative conditions, spinal cord injuries, immunological conditions, cardiac diseases, pulmonary disorders, ophthalmological diseases and injuries, and urological diseases as well as cosmetic indications. Many of these marketing claims raise significant ethical issues given the lack of peer-reviewed evidence that advertised stem cell interventions are safe and efficacious for the treatment of particular diseases. Such promotional claims also generate regulatory concerns due to apparent noncompliance with federal regulations.

Unfortunately, these US businesses are less unlike the stem cell tourist clinics that I've written about before than I would like.

Where's the FDA?

I thought about perusing the list of clinics in more detail and picking out the most egregious examples other than RMG, but that can wait for a potential future post. (It is, after all, a holiday weekend, and we'll be having visitors.) So instead I'll move on to conclude with the question that many of you are probably wondering after seeing an example such as treating autism with stem cells: What the heck is the FDA doing?

This isn't as simple as it sounds. For one thing, as noted in Turner and Knoepfler's supplemental methods section:

However, it should be noted that according to 21 CFR 1271.3 (d) (4), minimally manipulated bone marrow for homologous use does not require pre-marketing approval by the FDA. 21 CFR 1271.15 (b) states that facilities removing cells or tissues from an individual and implanting those cells or tissues in the same individual during the same surgical procedure likewise do not require premarketing approval. In addition, federal regulations contain detailed criteria specifying when autologous or allogeneic cells can be used without first obtaining FDA premarketing approval. These criteria are identified in 21 CFR 1271.10. We mention these important sections of 21 CFR 1271 for a reason. Our goal was to identify businesses that engage in direct-to-consumer marketing of stem cell interventions and fit within our inclusion criteria. Judgments about regulatory compliance or noncompliance had no bearing on whether specific businesses were included in our database. Federal regulations governing marketing, manufacture, administration, and registration of cell-based interventions are complex, products are classified into different risk- based regulatory tiers, and we in no way wish to claim or imply that inclusion of particular businesses in Supplemental Table 1 means that they are noncompliant with federal regulations. Such determinations, as well as other assessments of regulatory compliance, must be made by legally authorized regulatory agencies after rigorous evaluation processes.

This is, of course, the reason why so many of these businesses offer—or claim to offer—bone marrow or adipose stem cells. If they don't manipulate the cells too much, they can skirt FDA regulations, although the FDA is moving to crack down on unproven stem cell treatments and have started to issue warning letters. It's a complex issue, but it's hard not to look at the number of clinics and the breadth of health claims documented by Turner and Knoepfler and not come to the conclusion that there is a serious problem here. It's also clear that big money and political interests are hindering the FDA. For example:

Some proponents of deregulation argue that current federal regulations governing the advertising, processing, and administration of autologous stem cells are too onerous and have resulted in few approved stem cell therapies reaching the American marketplace (Chirba and Garfield, 2011, McAllister et al., 2012). The REGROW Act is an example of the current push from some political quarters and even from some individual stem cell researchers for lowering safety and efficacy standards for adult stem cell-based interventions. However, we found that hundreds of U.S. businesses are already promoting stem cell interventions for an extraordinary range of clinical indications. Advocates of deregulation will perhaps be pleased by our findings that many putative stem cell interventions are currently available for sale in the U.S. In contrast, proponents of a marketplace in which cell-based therapies have traditionally been tested for safety and efficacy and subject to pre-marketing review by the FDA will likely be concerned by how many U.S. businesses are currently marketing stem cell interventions. We are particularly concerned that we found many advertising claims related to ALS, Alzheimer's disease, Parkinson's disease, and many other conditions for which there is no established scientific consensus that proven safe and efficacious stem cell treatments now exist.

The REGROW Act sounds a lot like the 21st Century Cures Act, ideologically-driven "solutions" that mistakenly argue that the way to let loose a torrent of cures for every disease imaginable is to "unleash" the power of the market through deregulation. In the case of the 21st Century Cures Act, its proponents propose to give the NIH a bit more money in return for weakening the FDA. It's basically a solution to a nonexistent problem. The REGROW Act is cut from the same cloth, as it would allow provisional approval of stem cell therapies without phase III trials and establishing a conditional approval paradigm. Together with "right to try" laws, the REGROW Act and the 21st Century Cures Act are of a piece with a libertarian, free market-driven agenda to hamper government regulatory agencies. Fortunately, the the REGROW Act v.2.0 appears to be going nowhere fast. Meanwhile these stem cell clinics are scrambling to deny that they are doing anything unethical, illegal, or dangerous.

Perusing some of the websites, I couldn't help but notice how dubious stem cell therapies seem to have found a comfortable home in alternative medicine clinics. Perhaps the most blatant example I found was the Purety Family Medical Clinic, which advertises itself as "holistic medicine specialists for women, men, and pediatrics as well as prolotherapy, IV, ozone, chelation, HRT and FMT." Right alongside stem cell injections for "badly injured or degenerated tissue," Purety also offers chelation therapy for "heavy metal detoxification," high dose vitamin C drips, ozone therapy for cancer, naturopathy, fecal transplants for a variety of illnesses, and, yes, homeopathy, The One Quackery to Rule Them All.

Unfortunately, given how potentially promising stem cell therapies are, right now they are tainted by association with quackery like that described above. Basically, stem cells are being sold as being every bit as magical as alternative medicine like homeopathy. However, as PZ Myers points out:

Stem cells are not magic. They are plastic cells that are pluripotent — they can differentiate into a variety of different tissues. But they need instructions and signals in order to develop in a constructive way, and the hard part is reconstructing environmental cues to shape their actions. They're like Lego building blocks — you can build model spaceships or submarines or houses with them, and they have a lot of creative potential, but it's not enough to just throw the Lego blocks into a bag and shake them really hard.

That's what these stem cell clinics are doing, injecting stem cells and hoping they do their thing without knowing how the body induces them to do their thing, all while charging patients large sums of money for the privilege of being in what is in essence a poorly designed, poorly regulated clinical trial.

I don't know about you, but if I were a legitimate advocate of stem cell therapies, I'd be very disturbed at how easily stem cell therapies are currently "integrated" with pure quackery like chelation therapy and homeopathy. Being so easily associated with clinics like Purety is not a good way to make stem cell treatments respectable, but it is a good way to make a lot of money if you aren't that concerned with medical evidence or ethics—at least until the next Jim Gass hits the news.

oracknows Sun, 07/10/2016 - 21:03