Do three blinded US Stem Cell clinic patients with major or complete vision loss constitute a significant adverse outcome?
I would say so and a new paper details how this happened apparently at a particular publically-traded South Florida stem cell clinic business.
You can see the damaged retinas of one such patient below in an image from a new NEJM paper reporting the severe adverse outcomes. The red areas are hemorrhaging with other substantial damage to the retina as well.
How did this all happen?
Last year the story began to break of multiple patients alleging they had been blinded by different businesses in South Florida. Dr. Thomas Albini presented on some information on this at the FDA meeting last fall, but things weren’t entirely clear. Back then there were also indications of lawsuits by patients related to alleged vision loss due to experimental stem cell offerings against various parties involved.
Now we have more details on some of the cases in this new NEJM article (Kuriyan, et al.) in which the authors attribute these patients’ experiences to a withdrawn “trial”, NCT02024269, which lists Bioheart (now known as US Stem Cell, Inc.) as the sponsor. I put “trial” in quotes because it was withdrawn and also because as best as I can tell this wasn’t a traditional FDA-approved trial of the kind normally based on pre-clinical data and an IND. US Stem Cell, Inc. is a publicly-traded company ($USRM) and its stock has been all over the place this year. I’m not aware of US Stem Cell having FDA approval for what it is doing.
The NEJM article oddly does not mention Bioheart or US Stem Cell, Inc. by name as the place where the patients were given the stem cells, but the authors do clearly link them together and other information further supports this connection.
For example, US Stem Cell, Inc. leader Kristin Comella acknowledged last year in an NPR interview that two of their patients had retinal detachment following interventions received from the company. From NPR:
“Comella acknowledges that two of her clinic’s patients suffered detached retinas after getting stem cells injected into their eyes. As a result, the clinic has stopped treating eye conditions.”
You can read my 2015 interview with Comella here. I have reached out to her more recently to ask for her perspectives on the situation with these patients, but gotten no reply.
The NEJM article goes through the cases of the three blinded stem cell clinic patients who had received adipose stem cell injections into their eyes:
“We report three cases of vision loss after patients with AMD received bilateral intravitreal injections of autologous adipose tissue-derived stem cells at a stem-cell clinic, which was the study site for the fourth trial described above (NCT02024269). After treatment, in June 2015, the patients were referred to two university-based ophthalmology practices.”
There are so many questions here.
Why would someone think that fat stem cells could be used safely and effectively in eyes? To me as a stem cell biologist that doesn’t make sense.
Why would an IRB approve this kind of risky approach?
Why did they inject into both eyes at once?
And a biggie: if preclinical testing had been done and rodents had been given equivalent transplants, would some of the animals have gone blind? If so, could that have prevented this tragedy?
Since US Stem Cell, through a subsidiary called US Stem Cell Training, sells some kind of stem cell training to others to do stem cell interventions, is that spreading risks to patients even further? Notably on the US Stem Cell Training website none of the personnel listed as doing the stem cell clinical training are MDs. Why is that?
Is this just the tip of the iceberg for negative stem cell clinic outcomes given that there are around 600 such clinics in the US today largely operating generally without FDA approvals, lacking preclinical data to support what they are doing, and experimenting on thousands of patients for profit?
Where was the FDA in all of this and are they doing anything about it now?
In the same issue of NEJM there’s an opinion piece by top stem cell researcher and Harvard Med School Dean George Q. Daley comparing this unfortunate situation to the very different stem cell clinical research done in a 2nd paper (also published in the same issue and about which I will blog in coming days if I have time) that he sees by contrast as having been done in a responsible way.
South Florida seems to be a risky hotbed of stem cell clinics and beyond US Stem Cell, another non-FDA approved vision stem cell study there called the “SCOTS trial” has been controversial as well with a number of patients alleging they were blinded.
The clinicaltrials.gov website remains a great, but also very problematic resource. Many patients seem to view anything listed on there as a legitimate, NIH-approved full-blown clinical trial and some clinics encourage that view, but that’s clearly not the case. I interviewed the leader of clinicaltrials.gov in 2014 and problems were already apparent to me back then from that discussion. Clinicaltrials.gov needs to provide patients with much more information (e.g. IND status, fee as inclusion criteria, etc.) and consider excluding certain listings. While it is quite possible that it lacks the budget, the flexibility, and/or the authority to make such changes quickly, a lot is at stake. They need to make changes asap.
I hope that the NEJM paper on the 3 patients will raise awareness and spark meaningful actions to protect stem cell clinic patients moving forward.
Looks like US Stem Cell Inc is now being promoted in a penny stock pump and dump promotion http://streetregister.com/2017/04/06/after-recent-developments-trading-in-us-stem-cell-inc-otcmktsusrm-increased-momentum/
Paul,
Thank you for continuing to give us the latest on stem cell research and results, both good and bad, regarding this. My husband sent me the NEJM article, not knowing I had read your blog’s citation. I have been researching stem cells since losing most of my sight in my left eye. My retina detached while I was in a foreign country and after having surgery, I returned to California to be faced with 8 more surgeries, since the 1st one caused secondary glaucoma. I went through what Kubler-Ross describes as stages of grief and was initially ready to go to China if I found anything that worked. I got a big “Don’t do it!” from my Glaucoma guy.
Being legally blind in one eye and having a cataract in the other, meant that I could some day face surgery to get that cataract removed. Any surgery is risky.
Re: the SCOTS study: I, too, reached out to Dr. Steven Levy, asking for data. I did not get a reply. I found clinical trials.gov, thinking it was legitimate regarding using the scientific method in their studies. My Retina guy told me that anyone (?!) can post their trial on that site and that I should never have to pay to participate in a research study or trial.
I have read your other blogs and still hold out hope that there will be more cures for all kinds of ailments. Dr. Takahashi’s work looks promising. I am with the group that thinks, come on, hurry up already! My lack of depth perception, peripheral vision and having a constant blur on my left has been a challenge for my brain to adapt to, yet I feel lucky to still have 20/50 vision with my right eye.
Keep on keepin’ on! I look forward to the science of stem cell research and do not want to believe my specialists when they say, “Maybe in 20 years” they’ll have a cure for repairing my optic nerve and retina.
None of this would have happened in the first place if the federal government hadn’t defunded and demonized embryonic stem cell research ever since its existence even began
@admin can you email me the list of all of the clinics that you mention in your paper? The link on your blog doesn’t work? IM curious on the differences of them.. Thanks in advance!
This isn’t about science, and it isn’t even really about a stem cell clinic or a stem cell company. It’s about politics, and it’s about religion.
None of this would have happened in the first place if the federal government hadn’t defunded and demonized embryonic stem cell research ever since its existence even began. And as soon as Obama lifted the ban, people from the religious right immediately started the Shirley vs. Sibelius garbage to keep up the ban. We would have a safe, legal cure for the most common cause of blindness, macular degeneration (at the very least.) Ocata would have been able to do their work and continue the studies instead of having to go out of business. The patents would never have been sold to Astellas. This all happened because of politics and because of the (so-called) Christian right. If religion stayed out of politics, these people would have had a real cure instead of being desperate enough to seek out illegal stem cell clinics. Mike Pence has fought against stem cell research in the past, so does anyone honestly think that the ban on funding ISN’T going to come back??
Science is the wrong place for any religion.
Adverse events, including death, can occur in clinical research; and they often do more than anyone likes. Highlighting and sensationalizing one study or even several studies with bad outcomes should not be used to vilify an entire field of emerging experimental medicine.
Most current experimental therapies in BOTH private clinics AND preciously revered (in this blog) FDA-approved clinical trials are non-homologous in format. This common treatment approach reflects a generally overly urgent discipline that just uses the cells that are most readily sourced, whether the treatment basis makes sense or not. That being said, the heterologous stem cell healing magic hypothesis has not been disproved or discredited yet. There are in fact recently published sound clinical trials that provide evidence of beneficial non-homologous cell effects in some conditions. Not cures, but preliminary results supportive of non-homologous healing effects. Seemingly more rational stem cell therapies require that natural, tissue homologous stem cells are produced for treatments; but at the moment this requirement remains one of the singular challenges in stem cell biomedicine.
But getting back to the discussion at hand, I agree that more oversight is needed on what is going on in unregulated private stem cell clinics and under-regulated sponsored stem cell experimental trials. Here the ideals of FDA-approved clinical trials certainly do apply. Fully informed consent, documentation of adverse events, and stoppage of treatments that lead to unacceptable adverse events, followed by investigation of the basis for the encountered adverse responses and effects.
In well designed human research studies, we don’t learn only for the neutral and good outcomes. We can learn from the bad outcomes, too. A bad outcome is the risk that every patient takes, even when receiving an approved treatment in standard medical practice. This is why signing treatment consent forms is a routine of current medical practice (with malpractice suits as an important ancillary factor). However, this risk is often greater in the experimental setting. Pre-clinical animal studies can reduce it somewhat; but adverse events in animals are not highly predictive for people. Hence, patient studies with dose escalation and careful monitoring often occur with treatments that have left a wake of dead rodents.
In science and medicine, it is crucial that we make policy decisions based on comprehensive data, and not jump to rash conclusions based on a few selective sensationalized accounts. When we do the latter, we confound the actual state of affairs, compromising our ability to achieve the highest quality science and the best quality of care for the suffering among us.
James at Asymmetrex
I was not able to access the paper written by Daley as it is by subscription only. Based on your knowledge and exposure, why can’t you write something for us consumers that will help us avoid such tragedies with our own problems and treatments. With Trumpism, the NIH and FDA standards–wanting as they are already–will only decline further, maybe by a lot, as with most other federal agencies. That is the avowed aim in this administration.
Tell us, by name, who we can trust, which places have honesty and integrity and care more for safety & efficacy than for money and self-aggrandizement. Is there really such a place in the US? Going abroad is even riskier.
kk
Thanks, Jeanne! I’m writing something up on that paper.
Good article. Couldn’t agree more with you about clinicaltrials.gov. Since all legitimate clinical research trials are listed there, viewers often mistakingly perceive everything listed as legitimate and following acceptable research guidelines with oversight from a university, hospital, etc. There are many observational studies listed on the site as well and studies offered by for-profit clinics, requiring payment for participation, but not measuring success with quantitative measures. Self-reported data from questionnaires is not an acceptable measure of the effectiveness for stem cell treatment if it is the only measure. Getting these questionable studies posted on the clinicaltrials.gov website legitimizes them and increases their credibility. Like many others, as a PPMS sufferer, I constantly look for anything that could help stop or slow the progression and have seriously considered stem cell treatment because there is nothing else available so what have I got to lose, but so far, Ive been able to come back to reality and make data driven decisions. No one wants to believe more than me, but I don’t see the positive data and in fact see a lot of negative data. Unfortunately, the ancillary, self-reported success is compelling and that is why they make the profits that they do.
The other paper, from Masayo Takahashi in Japan, describes how a clinical trial for macular degeneration should be done. It’s valuable to read that article to compare it with the paper reporting the appalling results of unregulated cell treatment for the same disease.
Absolutely agree, having gone through the process of succesfully submitting two INDs and a CTA in Europe for AMD and Stargardts Macular Dystrophy for an embryonic stem cell RPE clinical trial, it is very important that investigators and patients understand what the necessary steps are to assure a reasonable level of safety to the patient.
These opportunistic clinics not only prey upon the desperate but also create a more difficult path to evaluate potentially beneficial therapies and may even create additional hurdles to having products approved.
I hope that there will be significant repercussions on these pseudo clinics before more people are seriously injured or worse.