But what exactly is the ICMS about, how did it burst so suddenly onto the stem cell scene, who are its leaders, and what motivates them to promote expensive, wild-eyed stem cell schemes without independent oversight or evidence of safety and efficacy? The tale is long and very, very twisted, so I'm afraid I'm going to need to ask a bit more of your time than usual to explain why I think the ICMS is not all that, and much more than, it seems.
Let's go back to the roots. If you ever find yourself in Salem, Oregon, try heading south of city center to a downscale neighborhood near the municipal airport and Stone Quarry Lake. Drive a few hundred meters down 22nd St, to where the sidewalk ends just east of McGrath’s Fish House and Prestige Auto Repair, and you will find the global headquarters of the ICMS: a post office box at 2667 22nd St SE, Salem, OR 97302. If you need directions, the ICMS graciously provides them on its Facebook page, although I generally prefer Google Maps to Bing, if only for the pictures...
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The bleeding edge of stem cell therapy... |
The Salem P.O. box is a convenient place for ICMS executive director, Salem-based David Audley, to pick up the mail, and just one hour by car from Oregon Health Sciences University in Portland, where former ICMS president, Michael D. Freeman (2009-2012), teaches forensic epidemiology. Freeman, originally a chiropractor, is himself no stranger to Salem - the ICMS mailbox is less than 10 miles from the clinic where, in 1991, he and four other chiropractors (including Freeman's father) were accused by the state of fraud and racketeering for using a doohickey known as a Toftness Device (but as the court documents note, also referred to as a "radionics detector" or "Freeman device"). The online Museum of Quackery points out that these *ahem* diagnostic tools were rigged together from PVC tubes and couplings. The defendants asserted that the device they used in their practices was, however, substantially different from the TFD, as it included "rubbing plates" and anyway, had been approved by the Oregon Board of Chiropractic Examiners - so there! In any case, the case was dropped even though the chiropractors did not deny using these devices, giving Freeman a defendant's-seat view of the amazing healing power of wriggly legal maneuvers. More recently, he seems to be putting this knowledge to frequent use as an expert witness in various cases, including testifying for the defense in the Casey Anthony trial, and giving a non-self-reflective lecture on "Exposing, defusing and debunking junk science" in Los Angeles this January.
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| Hat tip, Eugene Register-Guard. |
I don't know what led Freeman out of chiropractic and into the arms of epidemiology, expert testimony, and his longtime partnership with Chris Centeno, owner of Regenerative Sciences (of Regenexx™ and USA v Regenerative Sciences fame), but PubMed shows their first co-authored publication to be from 2004 ("Waddell's signs revisited?"). This co-authored comment in Spine (sorry, paywall) and their next six papers have nothing to do with stem cells, but rather various forms of spinal injury, with a focus on whiplash. For the past few years I thought this was anomalous, and not particularly worth commenting on.
At this point in the story, I have to give credit to an anonymous friend of the blog who pointed out that the Spinal Injury Foundation itself evolved from a different website, Whiplash 101, a resource used to, among other things, direct patients to apply for a one-hour consultation with Centeno for $350. Centeno also founded an (also now-defunct) online Journal of Whiplash and Related Disorders, for which he and Freeman, unsurprisingly, served as co-editors-in-chief.
Centeno and Freeman's Spinal Injury Foundation ramped up its marketing game even as they were careening off toward the stem cell fringe, running awareness days and other fundraisers including, in 2007, the novel concept of rewarding anyone who donated $1495 to this whiplash organization with a chance to drive a Lamborghini, Ferrari, Bentley, or other speedmobile around a race track in the Rockies. The promotional page for the event included the cautionary text: "If you can't find a car you like, consider psychiatric help or high-dose antidepressants."
But then last month I stumbled across some real expert testimony, by orthopedic surgeon George Muschler, in the FDA vs Regenerative Sciences case (via a link in this story on HuffPo). At 107 pages (48 pf which are Muschler's CV, and several of which have been redacted), this is not for the short of time. But for anyone interested in seeing what an actual scientifically-minded M.D. makes of the published claims in support of Centeno's Regenexx™ stem cell product, it is definitely worth a read. My one-word summary would be: scathing. For the curious, I have excerpted a few choice passages below:
Based on these observations, while I have no reason to question the motive of Dr. Centeno et al. to provide service to patients, I am concerned at this point that continued progress along the direction that has currently been established may be degenerating into an undisciplined and unfocused and even groping and wishful fishing expedition. The process that has been established does not appear to be subject to adequate oversight at the level of the IRB. From the personal level, this has the risk of exposing hopeful patients to a broad range of unnecessary and unproductive clinical therapy attempts under the banner of a “research investigation” that is, in fact, incapable, by design, of detecting the very treatment effect that RS purportedly hopes to demonstrate. On the medical level, I am concerned that the studies, as proposed, are being conducted using a culture expanded cell product that has not yet been adequately characterized. Furthermore, product specifications for quality assessment have not been defined, specific release criteria are not articulated, and the product has not been subjected to a rigorous assessment of safety that satisfies contemporary practice standards. [Muschler declaration, p. 31]and..
According to the paper [referring to (Centeno CJ et al., Safety and ComplicationsReporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells usingAutologous Platelet Lysate Technique, Current Stem Cell Research & Therapy, 2010;5:81-93)], four of the six authors (Centeno, Schultz, Cheever, and Robinson) have equity ownership in RS. Centeno 2010 article at 81. Another author (Marasco) has equity ownership in NeoStem, a company to which RS has reportedly licensed the Regenexx procedure in Asia. http://www.regenexx.com/2009/05/regenexx-in-china/ (November 22, 2010). Thus, all but one of the authors in this report have direct financial conflicts. Of particular note, Dr. Centeno and Dr. Schultz served as the only two reviewers charged with screening follow- up MRI scans for evidence of abnormal growth or tumor formation. Centeno 2010 article at 82. They also served as the only two adjudicators of patient complaints. Id. at 83. [Muschler declaration, p. 38]and furthermore...
Although bearing more on the ethical context of these studies than their scientific context, the IRB overview of these studies warrants brief discussion. The IRB that took responsibility for review, approval, and oversight of the studies authored by Dr. Centeno is identified as the Spinal Injury Foundation IRB. In the case of the Centeno 2010 article, the paper states that treatment of the “Group 1” patients was approved by the Spinal Injury Foundation IRB. Centeno 2010 article at 81. No mention is made of any IRB approval of treatment of the Group 2 patients discussed in that study.
The TL;DR summary: Centeno and Freeman were leaders of a separate, now-defunct organization (Spinal Injury Foundation) prior to becoming the first and second president of the ICMS, and said organization was tasked with, among other things, providing the institutional review of a body of research behind Centeno's Regenexx™ product line that one expert noted as being at risk of "degenerating into an undisciplined and unfocused and even groping and wishful fishing expedition." Freeman responded to the FDA's expert declarations here, and Regenerative Sciences posted a chronology here.From records provided to me, it appears that Dr. Centeno has an unusually close relationship to the Spinal Injury Foundation IRB: Dr. Centeno was the registered agent and Medical Director of the Spinal Injury Foundation. See 2009 EIR Attachments 6-7 (Kreuzer Dec. Exhibits 19-20). It should be noted that Dr. Centeno apparently recused himself from voting on the IRB’s approval of the studies. It is not clear if he was also excluded from the review and discussion of these protocols and/or if the voting records of IRB members were secret, so as to minimize potentially biased influence of a professionally and financially conflicted member. It should also be noted that John Schultz, M.D., and Michael Freeman, Ph.D., who are listed as co- authors on some of Dr. Centeno’s publications regarding the RS cultured cell product, were also members of the SIF Board of Directors.It is of potential significance that, according to the current (November 22, 2010) Spinal Injury Foundation website (http://www.spinalinjuryfoundation.org/), the Spinal Injury Foundation is now operating under a different name, International Cellular Medicine Society, which is located in Oregon. Among the nine points in the ICMS mission statement is the goal: “To establish that when A-ASCs are minimally culture expanded, are not biologic drugs but rather human tissue.” http://www.cellmedicinesociety.org/physicians/join (accessed November 22, 2010). Dr. Centeno also serves in a leadership role in ICMS, specifically as the Medical Director. http://www.cellmedicinesociety.org/home/boards-and-councils/board-of-directors (accessed November 22, 2010). [Muschler declaration, p. 40]
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| Freeman and Centeno: the early years |
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| http://web.archive.org/web/20050210122622/http://whiplash101.com/ |
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| Snap your neck for whiplash! It was in around 2005 that Centeno showed visible symptoms of the stem cell itch (his first n=1 stem cell paper was published the following year). We know this because 2005 was the year he sold the Colorado professional corporation known as "Christopher J. Centeno, M.D., P.C." to Florida-based company PainCare Holdings for $3,250,000 in cash and 1,132,931 PainCare shares valued at $3,750,000. What Centeno (the person) specifically did not sell, however, was intellectual property surrounding a certain stem cell process he had cooked up while running the Spinal Injury Foundation, and Whiplash 101, and his busy clinic, and the whiplash journal, without (as far as the literature reveals) any previous published indication of interest, ability, or experience in stem cell research and development. Another stem cell miracle! Stem Cell Intellectual Property . (i) Any and all activities and work product of Sellers regarding regenerating damaged or degenerated tissue, including, but not limited to, the development and sale of a turnkey solution for the isolation, processing and expansion of autologous stem cells for such regenerating damaged or degenerated tissue and the pursuit of any and all business opportunities available as a result of such activities; (ii) any and all work and work product of Sellers related to the isolation, processing and expansion of autologous stem cells; and (iii) any and all work and work product of Sellers related to the isolation, “processing” (as hereinafter defined), expansion and “storage” (as hereinafter defined) of autologous stem cells and/or storage of stem cells, Mensenchymal stem cells, chrondrocytes, or other unnamed progenitor cells, including but not limited to the development of short and long term stem cell storage plans. “Storage” means the freezing or otherwise storing stem cells in a suspended activity state for later use. “Processing” means includes but not limited to manipulation, expansion, isolation, purification, and/or differentiation of autologous stem cells or any stem cell line. [from PainCare - CJC Asset Purchase Agreement] The PainCare deal turned rancid after that company was accused of overstating its revenues, and became subject to multiple class action suits. Centeno was able to regain his eponymous assets for a small fraction of the original selling price. Not long after this settlement, Centeno and Freeman were cobbling together the first version of the ICMS, known as the American Stem Cell Therapy Association (ASCTA) at www.stemcelldocs.org. This group, whose founding members included Freeman, Centeno, and Centeno's partner John Schultz, as well as, o-ho!, Centeno's fellow University of South Florida alum Zannos G. Grekos (someone readers of this blog should certainly recognize), espoused the same basic set of values that characterizes the ICMS, including an emphasis on the de-regulation of autologous stem cell products, and a strange insistence that dark forces stand in the way of stem cell progress (with enthusiastic support from the bleachers at Stem Cell Pioneers, and its own, now apparently static, patient info portal, safestemcells.org).  Over the years, the ICMS has embraced a galaxy of stem cell proprietors, the likes of Korea's own Booger-cloning Ra Jeong Chan [wayback], and Jorge Tuma [wayback] and Augusto Brazzini [wayback] of Peru on various councils, although you won't find much trace of them on the current version of the site. But even after making the transition to an "international" society, the group has maintained some oddly America-centric positions, including the oath it requires prospective board and council members to take prior to entering service (secret decoder ring not included):
Note that this vow makes no mention of the substantively similar provisions for the regulation of human cell and tissue products in the EU, UK, Canada, and other countries, which seems strange for a group that labels itself "international." Whatever the case, the ICMS' general strategy seems to me to have consisted from Day One of: 1) the promotion of treatments based on human cells that have not been subjected to rigorous scientific study or independent oversight; 2) the encouragement of healthcare providers to challenge and indeed violate existing laws established for the protection of patients; and 3) the invocation of baseless conspiracy theories and legal attacks when such practices are criticized and prosecuted (which I call the "tout, flout, and pout" model). In a remarkably short time, the ICMS whipped itself into the semblance of a credible organization, complete with various guidelines for budding stem cell entrepreneurs, an Offshore Clinics Report (which if nothing else serves as an excellent scorecard for what clinics have signed up with ICMS), another patient portal (Stem Cell Watch), a newsletter, a Treatment Registry for which patients were charged $350 to store their own treatment information, which at 750 registered patients and counting means at least another $262,500 for this NPO (and as I noted in an earlier post, the inclusion of RNL Bio in the ICMS Treatment Registry at $50 per patient on the provider side would potentially have cost that company $400,000+), and a Clinic Accreditation Program for clinics willing to pay the society for a fig leaf to plaster on their website (more on this below). Without apparent irony, the organization also recently announced a deal with an insurance company to provide malpractice insurance for their members (many of whom have built businesses around putative stem cell injections supported by guesswork, anecdote, slapdash research, and "expert" hand waving). This, in my view, may prove to be one of the most valuable member service ICMS has introduced to date, and I'm sure it will see plenty of use....  Short of "stem cell" cred? We've got you covered. The accreditation program, however, is their marketing master stroke, as it lends a veneer of authenticity and a web-friendly banner to otherwise incredible stem cell-flavored medical claims made by enrollees. The first outfit accredited by the ICMS is the Regenerative Medicine Institute of Tijuana, Mexico. The ICMS process, which was originally announced as taking a rigorous 18 months, took less than a year (the RMI application for accreditation was announced on March 15, 2011, and the ICMS approval announced on February 24, 2012). In the more recent release, ICMS executive director and marketing whiz David Audley praised the clinic, saying, "The safety profile has been excellent. We have tracked patients over at least two follow ups and a minimum of six months and not seen a single cell-related adverse event." This is remarkable, as only four months earlier the ICMS announced an investigation of the death of a patient treated at the same clinic, and then just two weeks later announced the expected finding that its paying customer was not to blame, based on what appears to be only partial evidence (e.g., no autopsy), interviews, and testimony. No mention is made of the identities of the three physicians who conducted the investigation on the ICMS' behalf, or of the ethicality of subjecting a a frail ('"the patient was told by his family physician that he was very weak and that another infection would most likely be fatal") 74-year-old man with lung disease to an uncontrolled, for-profit medical experiment in Mexico. The RMI, which is operated by the Angeles Health International medical tourism network and connected to the website www.stemcellmx.com, is itself worthy of another long and detailed post, particularly given its close relationships with Bioheart and Stemedica, two US-based companies with registered clinical trials (here, here), and its extraordinarily long and diverse list of ungrounded treatment claims. By this, I mean Parkinson's disease, and Alzheimer's disease, and traumatic brain injury. And stroke and cerebral palsy and multiple sclerosis. And heart failure! And don't forget macular degeneration and glaucoma and diabetic retinopathy. And diabetes and kidney failure to boot! The ICMS has accepted other applications as well. Take World Stem Cells, LLC, for instance. Located in Cancun, Mexico, this clinic flies the ICMS badge of shame right on the top page of its website, and applied for accreditation last May, which if the RMI experience is any indicator, means the results of the "18-month" review are already overdue. I don't feel like typing the long list of World Stem Cells' treatment claims in its entirety, so please feel free to click away below.  Ever the businessman, Chris Centeno has been keeping busy after being replaced by Freeman as head of the ICMS, and unceremoniously dumping his previous NPOs and the whiplash journal he launched. In 2010, he tried unsuccessfully to sue the FDA (revealing in the process that by June of that year his company, Regenerative Sciences, had already performed 43 unapproved treatments earning $236,500 and banked 242 patients' cells at $5,000 - $8,000 a pop; i.e., $1.2 to 1.9 million in revenue), and is now locked in a legal fight over an injunction the FDA sought against his company Regenexx. He has licensed his cultured cell product (Regenexx-C) to partners in Argentina and China, and set up a stem cell treatment subsidiary in the Cayman Islands. He is also a planning committee member and speaker for this year's one-day ICMS-sponsored session in Hollywood, FL, held in conjunction with the annual meeting of the Age Management Medicine Group, alongside other such alt-med luminaries as Jeffry S. Life (alternative medicine is, anyway, familiar turf for Centeno).  Yes, that Jeffry S. Life. So forgive me for my skepticism. Having watched the crass casuistry, hucksterism and vampire squid ethology that have characterized the organization so far, I can't help but think the real meaning of "ICMS" is International Cellular Marketing Service. It is too soon to say whether things will change under their new leadership, and best of luck to Dr. Rodriguez and the latest generation of ICMS leaders in setting the group on a course to science-based medicine. But given the proven profit potential of many other companies selling variations on the stem cell miracle cure, and the growing demand for weaselly workarounds to independent pre-marketing safety and efficacy requirements of the sort the ICMS has specialized in to date, I wouldn't bet my life on it. And neither, my valued reader, should you. |
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