Patient gets cancer growing on spine from dubious stem cell treatment

A brief report in the NEJM today highlights the risks facing patients who get stem cell treatment from dubious clinics as one such patient recently developed a large spinal tumor.

Dr. Aaron L. Berkowitz and colleagues describe how this patient who received a mixture of several stem cell types from an overseas clinic was later diagnosed with a very unusual neoplastic growth on his spine.

stem cell tourism tumor

NEJM Figure 1a/b, showing massive spinal tumor (long, brighter region)

The data point to the tumor arising from the stem cell treatment as it was genetically distinct from the patient.

Oddly the cancer defied classification as a particular tumor type. This may in part be due to the fact that he was given a mix of embryonic, fetal neural, and mesenchymal stem cells. It’s unclear which cell type(s) might have led to the tumor. Notably he apparently didn’t get any immunosuppression, which raises the question of his own immune response to the transplants.

This patient received at least three transplants at different locations across the globe outside the U.S. While risks of stem cell offerings are higher in certain countries, there are many stem cell clinics here in the U.S. that sell stem cells without FDA approval and with little if any data to back them up.

The NY Times just published an article on this case and identified the patient as Jim Gass as well as providing more details including the start of the chain of events:

“I began doing research on the internet,” Mr. Gass said. He was particularly struck by the tale of the former football star and professional golfer John Brodie who had a stroke, received stem cell therapy in Russia and returned to playing golf again.

So Mr. Gass contacted a company, Stemedica, that had been involved with the clinic, and learned about a program in Kazakhstan. When Mr. Gass balked at going there, the Russian clinic referred him to a clinic in Mexico. That was the start of his odyssey.”

The impact of sports celebrities getting unapproved stem cell treatments and the press about such situations can be far and wide on the public.

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Mini-bios on some top finalists for Stem Cell Person of the Year

Heather_MainBy Heather Main

I was a little ashamed of myself that I didn’t know who half of the finalists were in Paul Knoepfler’s Stem Cell Person of the Year Award. I decided to look into it and find out what (or who) I have missed…..Interestingly, 3 of the 7 listed here are not scientists but instead are patients and/or patient advocates, showing the major impact these groups have on progression of our field. I have listed my write-ups of the finalists here alphabetically.

Bill Moss – FSHD sufferer, FSHD global foundation founder and chairman

Bill was diagnosed with FSHD (the most common form of muscular dystrophy) at 28 years old. The youngest child of a gardener, Bill became a masterful businessman and spent 23 years as a senior executive and Executive Director of a pre-eminent Australian investment bank before leaving at 52 years of age to pursue philanthropic initiatives. He has self-funded programs for industry development in Australian aboriginal communities, advocated for disability rights and established the FSHD Global Research Foundation. This foundation funded derivation of the first FSHD affected hESC and successful highthroughput modeling of the disease through development of an efficient protocol to differentiated them to skeletal muscle. 

Jeanne Loring – Academic researcher

Personally I think PluriTest (the bioinformatic test for assessing pluripotent status) alone earns Jeanne a spot in this ‘hall of fame’. Her lab also leads fields including the ‘Frozen Zoo’ (iPSCs from the endangered species), translational projects in arthritis, Alzheimer disease, Parkinson’s disease, autism, and addiction as well as creating collections of iPSC lines for disease modeling and ethnically diverse toxicity testing. Jeanne is also recognized for her public work in ethics, legal issues, clinical use, cell generation and clinical use, the legal implications of patents and stem cell tourism. In December she will be awarded the 2015 World Stem Cell Summit ‘Stem Cell Action Award for advocacy’.

Judy Roberson – Huntington’s Disease patient advocate

Judy is a registered nurse, who now works as a full time volunteer patient advocate for Huntington’s disease. This includes supporting the UC Davis Huntington’s Disease Clinic, the UC Davis Institute for Regenerative Cures, and CIRM (California’s Stem Cell Agency), including legislative advocacy. She was appointed as the first voting patient representative to the FDA Huntington’s Disease Advisory Committee and is past president of the northern California chapter of the Huntington’s Disease Society of America. Judy advocates for the role patient advocates play in driving stem cell sciences towards making the goals a reality.

Michele de Luca and Graziella Pellegrini – academic researchers/clinicians

Professor De Luca, and his principal collaborator Graziella Pellegrini, have worked together over 20 years, towards the use of human epidermal stem cell cultures for life saving burns treatments as well as treatment of repigmentation and piebaldism. The team has also established human limbal stem cell culture for sight restoring corneal regeneration. Michele De Luca is coordinating the first (successful) gene therapy clinical trial for junctional epidermolysis bullosa and studies the stem cell behaviours of epithelial stem cells. Professor Graziella Pellegrini is based at the Centre for Regenerative Medicine “Stefano Ferrari” at the University of Modena and Reggio Emilia and one of the principal scientists on the corneal repair system Holoclar ®.  Together they have achieved Europe’s first approved advanced therapy medicinal product (ATMP) to be integrated into health services for patients across Europe in the future. 

Robert Lanza – ‘child science star’, CSO of Ocata Therapeutics

Reading about Robert Lanza is like reading about a rock star. In TIME magazine’s 2014 100 most influential, in FORTUNE magazine and even suggested to be played by Ben Affleck if his work leads to restoring eyesight to millions. Son of a professional gambler and growing up in Boston, Massachusetts, the weirdest find is that at the age of 14 (1969), he partially induced melanin synthesis in chicken to change the colour of its feathers for a science fair project. While it is hard to find the details of this first study, at the age of 19, with the assistance of Stephen Kuffler and Joshua Sanes at Harvard Medical School, Robert published a complete change in pigmentation in Nature using nucleoprotein from the Harco chicken and a standard cross between the Barred Plymouth Rock hen and the Rhode Island Red rooster. Since this early fascination of genetics, Robert developed methods for deriving hESC lines from single blastomeres in an attempt to avert the ethical discussions of the destruction of human embryos and is now running clinical trials for macular degeneration with hESC derived retinal cells.  Robert is currently Chief Scientific Officer at Ocata Therapeutics (formerly Advanced Cell Technology).

Shoukhrat Mitalipov – academic researcher

Shoukhrat was the first to derive hESC through somatic cell nuclear transfer, publishing in Nature 2013. He is also the ‘father’ of 3-parent IVF where by ‘spindle transfer’ the genetic material of a donor oocyte is swapped out for the DNA of a mother who carries a mitochondrial disorder. This creates a new egg with ‘normal mitochondria’ and nuclear genetic information from the mother, which is then fertilised with the sperm of the father. The technique is successful in rhesus macaques but has not yet been tested in humans. Shoukhrat’s company Mitogenome Therapeutics appears to be pursuing 3-parent IVF in China, because it is not currently allowed by the FDA in the US.

Ted Harada – ALS sufferer and unproven stem cell treatment recipient

Another patient advocate, Ted has received two doses of fetal neural cells in his spinal cord from Emory University in Atlanta as an experimental treatment to slow progression of his ALS. While Ted showed improvement in limb movement, strength and dexterity from the first transplantation his abilities have slowly been regressing, leading to this second treatment. Ted is a strong advocate for “Right To Try” that patients’ choice to receive experimental treatments should be respected and will speed up innovation.  He challenges the idea that patients who are out of options may need to settle for ‘silver standards’ with novel FDA approved treatments taking 10 – 15 years and sometimes nearly a billion dollars. He feels that these patients do not have that time to wait. Refreshingly, he is not a fan of stem cell tourism and the Right-To-Try movement stipulates the treatment has to have completed an FDA phase I portion of a trial and been approved for phase II.

Stem Cell Tourism and Patient Education

By Zubin Master, PhD

What is the role of public education and stem cell tourism? What type of education is available to patients, caregivers and the public? Can public education actually change people’s minds such that they won’t undergo an unproven stem cell-based intervention (SCBI)? These are the questions I will discuss here. But first, let’s just give a brief description of stem cell tourism and outline some of the proposals discussed to stop this industry.

Stem Cell SymbolThe “Stem Cell Tourism” Industry and Ways to Curtail the Market

Briefly, “stem cell tourism” is a term used to describe an Internet-based, direct-to-consumer advertised industry where patients receive unproven SCBIs for a range of diseases and injuries. Many clinics offering unproven SCBIs are in countries with lax regulations and enforcement. However, these clinics are also increasingly popping up in highly regulated countries like the U.S., U.K. and Australia. The term “stem cell tourism” is misleading because patients may not necessarily need to travel a great distance to receive such interventions, and focuses on patient behaviors instead of others involved in this market including regulatory agencies and the providers offering them. Moreover, there are some real risks to stem cell tourism. Beyond patients being financially exploited, there are several reports of tumors, lesions, tremors, other problems, and even deaths of individuals receiving unproven SCBIs. And there seems to be a stem cell “treatment” for just about every disease and injury, no matter how severe or benign if the patient can pay anywhere from $8,000-$30,000. Clinics advertise for serious conditions such as heart disease, stroke, MS, Parkinson’s disease, ALS, and spinal cord injury among many others. You might have also heard of major NFL stars receiving SCBIs for sports injuries, movie stars receiving anti-aging stem cell treatments, and even a U.S. Governor receiving stem cells for chronic back pain. The fact that celebrities and public figures are receiving untested SCBIs is likely to make it seem that they are safe and effective and only bolsters the market. Yet there are very few bonafide stem cell treatments out there. While more clinical trials using stem cells are underway (1), it will become increasingly difficult for patients to discern between a legitimate clinical study and a fraudulent intervention. And because of all the hype, ethical issues, and misconduct scandals having to do with stem cell research, having patients become injured due to an unproven SCBI is not only bad itself of course, but also can seriously stifle the stem cell field.

Several strategies to curtail this market have been proposed. Many have turned to increasing regulations, which have been met with limited success. But using legal mechanisms alone to regulate this international market may only partially address the problem because clinics have been known to move to a more permissive environment and rebrand themselves continuing business without a hiccup. I have previously discussed how scientists on the ground can share lines and reagents responsibly such that providers will be unable to obtain the necessary materials to start-up a dubious clinic (2). One bioethicist has begun a letter writing campaign to the U.S. Food and Drug Administration alerting the regulatory agency to questionable practices happening in our backyard (3). And several others have discussed how professional regulation by medical licensing bodies can take punitive measures towards physicians who engage in stem cell tourism practices (4). Last but not least, another major approach to quell the stem cell tourism market is to educate patients, caregivers and the public about stem cell research, the clinical translation process, and the dangers of unproven SCBIs. Several major organizations have invested seriously in public education on unproven SCBIs including the International Society for Stem Cell Research’s (ISSCR’s) A Closer Look website (5), Stem Cell Australia’s The Australian Stem Cell Handbook (6), and the U.K. MS Society’s Stem Cell Therapies in MS handbook (7) among others. Along with collaborator Professor Timothy Caulfield at the University of Alberta, we have invested in designing and disseminating a patient handbook as well (8). Yet despite these notable efforts, overall there seems to be relatively little publically available comprehensive information on stem cell therapies and tourism.

Public Education and Stem Cell Tourism

We recently completed a study published in Cell Stem Cell evaluating 50 scientific organizations and 125 patient advocacy groups to assess the nature and quality of online information available on stem cell therapies and tourism (9). To provide a comparison, we looked at educational content on the science of stem cells, ethical and policy issues, and information about stem cell treatments and tourism. While 51% of scientific organizations and 21% of patient advocacy groups had information on stem cell science, both sets of organizations had equally low levels of information on unproven SCBIs ranging from 12% to 16%. These results show that while a few groups have made serious efforts to educate patients and the public, overall, there is little information out there (9).

Several have argued that education may not alter patient demand for unproven SCBIs because this approach depends on a rational actor model that assumes individuals will behave rationally and do what is optimal, based on the factual information presented (10). It is likely that patients become less risk averse and are willing to take their chances. The term “What have I got to lose?” is a common response by patients (11). Yet this view fails to adequately consider the value of public education on unproven SCBIs. First, education alone can never be thought to sufficiently achieve major public health goals in the absence of other interventions, and second, education should aim to provide more than simple functional literacy (e.g., knowledge on stem cell research and unproven SCBIs). It should aim to promote communicative/interactive literacy to improve an individual’s capacity to act independently on knowledge, increase self-confidence, and permit greater autonomy and personal empowerment (12, 13). For example, we know that some patients who have undergone unproven SCBIs have regretted their decisions (14) and so, may be public education might help some reconsider options. Education may also be helpful to counter some misinformation e.g., provider claims that SCBI are risk free if they are from their own body. And it may also help those seeking registered stem cell clinical trials recognize dodgy clinics advertising unproven interventions as “experimental treatments.” We must recognize that the question of whether educational campaigns on stem cell therapies and unproven SCBIs are effective remains empirically unassessed.

Many earlier health literacy campaigns on anti-smoking or college binge drinking have relied simplistically on the transmission of information and were of limited success because they did not necessarily promote healthy behaviors. However, more recently, strategies to improve public health messages have increased in theoretical sophistication and we know that message framing can help shape individual perceptions and motivate healthy behaviors (15). So perhaps education campaigns on stem cell therapies and unproven SCBIs can begin to incorporate message framing and other methods to more effectively promote healthy behaviors. More research is needed to better understand the effectiveness of current patient education on SCBIs and to improve our understanding of patient perceptions of risk and benefits of receiving unproven SCBIs so that we may better design more effective educational material.

Guest Post was written by Dr. Zubin Master, Assistant Professor at the Alden March Bioethics Institute, Albany Medical College and Research Associate at the University of Alberta’s Health Law Institute.

 

Links:

  1. http://www.futuremedicine.com/doi/abs/10.2217/rme.13.80
  2. http://embor.embopress.org/content/12/10/992.short
  3. http://www.nature.com/nm/journal/v20/n8/full/nm0814-796.html
  4. http://www.cell.com/stem-cell-reports/abstract/S2213-6711(14)00202-1
  5. www.closerlookatstemcells.org
  6. http://www.stemcellsaustralia.edu.au/AboutUs/Document-Library/Patient-Information.aspx
  7. http://www.mssociety.org.uk/ms-resources/stem-cell-therapies-and-ms-booklet
  8. http://bit.ly/scnpatientbooklet
  9. http://www.cell.com/cell-stem-cell/abstract/S1934-5909(14)00347-6
  10. http://onlinelibrary.wiley.com/doi/10.1111/1467-9566.12092/abstract
  11. http://www.hli.ualberta.ca/HealthLawJournals/~/media/hli/Publications/HLR/20-1-01_Rachul.pdf
  12. http://onlinelibrary.wiley.com/doi/10.1111/jlme.12017/abstract
  13. http://heapro.oxfordjournals.org/content/15/3/259.abstract?sid=a17026ab-7d9b-45a1-8940-0595be496f78
  14. http://www.couriermail.com.au/news/queensland/stem-cell-tourists-warned/story-e6freoof-1111117850053?nk=15a2309a141ae2a6d45231a0d4d2d994
  15. http://psycnet.apa.org/journals/bul/121/1/3/

Joanne Kurtzberg interview, Part 2: non-compliant stem cell clinics and the future of the stem cell field

I recently conducted an interview with Dr. Joanne Kurtzberg of Duke. You can see Part 1 of the interview here.

Today in Part 2, I asked Dr. Kurtzberg some broader questions about the stem cell field.

1. How concerned are you about non-compliant stem cell interventions here in the US as well as stem cell tourism? Perhaps because of my blog, I get contacted by parents of pediatric patients lately at least once a week about possible stem cell treatments for CP, autism, and other diseases. They generally are not asking about clinical trials, but rather expensive, dubious treatments abroad. What can we do about this situation?

I share your concern. I think the biggest risks associated with these therapies are infection, tumors, and immune mediated reactions, particularly when cells are delivered directly into the brain or spinal fluid.   The financial risks are high too.    Desperate families are not likely to respond to someone saying the treatment is not promising.   As an alternative, I take the approach of educating parents who approach me with similar questions about the questions they should ask about these therapies.  These questions include:

  • 1.  What kind of cells are being used in this therapy?
  • 2.  Where do the cells come from?
  • 3.  How are they tested for the risks of transmitting infectious and genetic diseases?  Specifically are they tested for HIV and hepatitis?
  • 4.  How are the cells prepared/manufactured?
  • 5.  How many patients have been treated with these cells?
  • 6.  How have these patients done?  What kind of follow-up is practiced/required?
  • 7.  Are there any toxicity/adverse reactions associated with the therapy?

2. On the positive side, what excites you the most about the stem cell field today?

I think the stem cell field has enormous potential particularly in the emerging fields of cellular therapies and regenerative medicine.  I think that development of this field will take 10-20 years and that it will take this long to see stem cells used in routine medical care.  I think it will be necessary to develop third party, ‘off the shelf’ products to fully realize the potential of cellular therapies.


3. Where do you think the field will be in 5 years? 10 years? 

In 5 years, I think we will be conducting early phase trials in some disease at the proof of concept stage.  I also think we’ll see major advances in immunotherapies, e.g. tumor and antiviral vaccines, cells to enhance immune reconstitution.   In 10 years I think we’ll have evidence from these trials to justify further development of specific cell therapies for specific diseases.  My best guess is that we’ll first see cells used to treat patients with stroke, ischemic heart disease, newborn and fetal brain injury and traumatic brain injury.

Philippines Investigating 3 Politician Deaths Allegedly From Stem Cells in Germany

The Philippine Medical Association (PMA) is reportedly (article from ABS-CBN News) investigating the recent deaths of 3 prominent politicians due to stem cell therapies via stem cell tourism in Germany at an as yet unidentified clinic.

The names of the politicians are unknown, but strangely enough today there’s another separate article on stem cells from the Philippine Daily Inquirer that mentions 3 politicians who have received stem cell treatments:

A number of politicians have been reported to have used stem cell therapy, including former President Joseph Estrada, Sen. Juan Ponce Enrile and former Sen. Ernesto Maceda.

Of course these men may not be the politicians referred to in the ABS-CBN piece. Maceda was quoted:

“I am now convinced that my stem cell therapy is effective and that’s the reason why I’ve been able to keep up with the rigorous campaign schedule,” he said. “I feel 20 years younger.”

In the past the German stem cell clinic X-cell was notorious for being linked to a baby’s death.

PMA president Dr. Leo Olarte commented on the more recent case:

“They were given stem cells from sheep, rabbits and animals. They died after one year, they had late hypersensitivity reaction,” he said.

It sounds like a very horrible situation. More information is needed to get the bottom of this.

The ABS-CBN Foundation, presumably the outfit responsible for ABS-CBN News that reported the 3 politician deaths, is an advocacy group of some kind in the Philippines that works with Olarte ( see him with Gina Lopez, Managing Director of ABS-CBN in the pic below).

Olarte stem cells

Stem cells are generating a lot of buzz in the Philippines and apparently stem cell interventions of various kinds are becoming more common including a supposed aphrodisiac stem cell potion called Soup. No. 7. Thus, efforts to reign in dangerous stem cell interventions there are very important. At the same time some in the Philippines such as Olarte want to promote stem cell tourism as well it seems. It’s a fine line to walk

For example, in commenting to ABS-CBN News in the same article as about the German deaths, Olarte seems to be playing up the state of stem cell interventions in that country more generally:

Olarte said the country already has experts, who are members of the Philippine Society for Stem Cell Medicine (PSSCM), competent to perform the treatment in the Philippines.

“We have more or less 400 specialists,” he said, even noting that the stem cell treatment in the country is much cheaper by 50% than what is being sold abroad.

I’m not so convinced that even these supposedly okay stem cell “treatments” promoted by Olarte are proven safe or effective either even if they are cheaper.

The deaths of the three politicians in Germany are disturbing news and highlight the care that must be taken in regulating stem cell interventions to keep patients safe.