One of the bigger stem cell stories in the past week was that hockey legend Gordie Howe had received a stem cell ‘treatment” that had “miraculous” positive effects after having a few strokes over the last couple months. (update: see more on celebrities rolling the dice on unproven stem cells here).
I am highly skeptical of this holiday miracle stem cell story and very disappointed in the media for essentially swallowing the PR (most often verbatim) without giving it more thought. How about doing investigative reporting or asking good, probing questions?
I like hockey. I went to many games when I used to live in Seattle as a fan of the Seattle Breakers. I have great respect for Mr. Howe, I’m glad he’s feeling better, and wish him the best. I have a bad feeling about this stem cell miracle story though.
So what’s the scoop here?
Howe received stem cells via a company called Stemedica along with a Mexican firm called Novastem. Let’s take a close look at the statement reportedly released by the Howe family about this stem cell intervention to identify some very puzzling and concerning elements that are red flags (emphasis mine):
“Following the press coverage of our father’s deteriorating medical condition, the Howe Family was contacted in late November by Dr. Maynard Howe (CEO) and Dave McGuigan (VP) of Stemedica Cell Technologies. McGuigan knew our family as a result of his previous employment with the Detroit Red Wings. Stemedica is a biotechnology company that manufactures allogeneic adult stem cells in its U.S. government licensed, cGMP facility in San Diego, California. Although no relation, Dr. Howe and his brothers Drs. David and Roger are hockey players and big Gordie Howe fans, having grown up in Minnesota. They wished to help our father by generously facilitating Dad’s participation in a stem cell clinical trial at Novastem, a licensed distributor of Stemedica’s products in Mexico.
Novastem (www.novastem.mx) is currently conducting federally licensed and Institutional Review Board approved clinical trials for several medical conditions, including stroke, using Stemedica’s stem cell products. At the time we were contacted, Mr. Hockey had been rapidly declining and was essentially bedridden with little ability to communicate or to eat on his own.
After reviewing the information on Stemedica and Novastem, our family decided to give our father this opportunity. On December 8, Mr. Hockey underwent a two-day, non-surgical treatment at Novastem’s medical facility. The treatment included neural stem cells injected into the spinal canal on Day 1 and mesenchymal stem cells by intravenous infusion on Day 2. His response was truly miraculous. At the end of Day 1 he was walking with minimal effort for the first time since his stroke. By Day 2 he was conversing comfortably with family and staff at the clinic.
On the third day, he walked to his seat on the plane under his own power. By Day 5 he was walking unaided and taking part in helping out with daily household chores. When tested, his ability to name items has gone from less than 25 percent before the procedure to 85 percent today. His physical therapists have been astonished. Although his short-term memory, strength, endurance and coordination have plenty of room for improvement, we are hopeful that he will continue to improve in the months to come.
As a family, we are thrilled that Dad’s quality of life has greatly improved, and his progress has exceeded our greatest expectations. Once again, we cannot emphasize how much you have fueled Mr. Hockey’s recovery and we thank everyone for their continued prayers and support.”
Let’s walk briefly through the highlighted parts one-by-one and think about the questions that they raise. Note that I’ve contacted Stemedica with some of these questions and have posted their replies here.
1. The Howe family was contacted by Stemedica. Did Stemedica reach out as a public relations effort?
2. The statement describing Stemedica is a red flag for a number of reasons. It includes very technical terminology not widely understood outside the stem cell biotech and regulatory field. Was it written by Stemedica or Novastem or others linked to these stem cell for-profits? Stemedica now says they did not write it.
3. Stemedica generously facilitated Howe’s clinical trial participation. This also is concerning. Did Stemedica and Novastem provide free ‘treatment’ to Mr. Howe, hoping for some positive, essentially free publicity?
4. The weblink to Novastem. Why would a statement by Howe’s family include a weblink to Novastem? Did the company ask the Howe family to do that in their statement as a way to get more customers?
5. Federally licensed clinical trials? This vague statement could be misinterpreted to mean that the trials are licensed by the FDA here in the US. Again, to my knowledge, this is not the case. Are they perhaps referring to licensed by the Mexican government?
6. “Truly miraculous” response. We’ve learned in the stem cell field to view statements about “miracles” related to stem cell “treatments” to be big red flags. As much as we might wish for miracles, there are few real medical miracles.
7. Tested improvement. Who tested Mr. Howe’s function? Family? Physicians? How was it measured objectively?
Sadly, this “family” statement has a feeling potentially of being like an ad for Stemedica and Novastem.
The bottom line is that I view this story of the stem cell ‘miracle’ for Mr. Howe as a troubling, complicated tale. It’s frustrating that the media did not do a better job of investigating it rather than just parroting what they were told. Again, I wish Mr. Howe and his family all the best, but it’s a reasonable question to ask if they’ve been used for publicity here. The end result of this kind of situation can be more patients getting unproven, potentially risky stem cell “treatments”.
It’s disappointing about all the secrecy around it as well — a good open testing and reporting regimen would provide more information for others, allow feedback to them and most importantly help remove doubts.
Would be nice to know — maybe this isn’t a miracle — but what if it helps 50% of patients live pretty full lives for an additional two years? What if it was a third of patients? And you could positively tie it back to the treatment, and others could independently say, “yep”.
I think a lot of the companies either a) don’t have faith in the treatments (snake oil) so they want to continue raking in $20K before being discredited; or b) are worried others might start using something similar (ie, greed). As for them, be the leader in a field and the money will come.
(got here from the Detroit Free Press article from today)
Cheers!
and another article
http://prohockeytalk.nbcsports.com/2015/01/11/howe-seeing-further-gains-following-stem-cell-treatment/?utm_content=buffer670e5&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer
a new article about this theme:
http://www.freep.com/story/sports/nhl/red-wings/2015/01/11/gordie-howe-dementia-detroit-red-wings/21596573/
It ist difficult to get information about Rafael Nadals treatment, if anybody has more information, please let us know.
I think his case could be very interesting, because the stem-cell-application seems to be successful (see above).
Take a look at his first match on the 2. of January.
Didn’t somebody else write about the Nadals case and point out that doctors probably didn’t use the type of stem cell treatment for him that most people thought they did? (No, really… I’m actually asking! 😉 I’m sure I read this somewhere, but where– and who wrote it– I don’t remember. It might have been here, maybe in a comment, but it might have also been somewhere else.)
Yes, that´s right, but what do you think about Rafael Nadals treatment? I think without curing his bones and cartilage, he won`t be able to play professional tennis again like he is doing right now.
Has he perhaps chosen a new stem-cell-therapy, which is really working?
Add me to the list of skeptics.
I have a request for those who believe that strokes and degenerative diseases can be reversed by injections of fetal nerve cells into the spinal cord and/or mesenchymal stem cells into the bloodstream.
Stem cell scientists know a lot about how stem cells act in the body. The fate of injected stem cells taken from another individual is rejection by the recipient’s immune system. It’s difficult to imagine how the activation of rejection response could help degenerative disease or stroke. But please offer an explanation if you have one.
Even if a person’s own stem cells, such as those from fat, are used, even if they survived in the bloodstream, they aren’t capable of becoming any cell type other than fat, cartilage, or bone.
So tell us, how does it work?
What do you think about PRP-therapy? it is already proven, that this kind of stem cell therapy could repair cartilage defects.
And what do you think about the therapy of Rafael Nadal
https://www.ipscell.com/2014/11/tennis-star-nadal-to-get-dubious-stem-cell-treatment/
Rafael Nadal has received a stem cell therapy, and now he started to play tennis again. Maybe this could be a small but the best evidence, that this therapy is working.
I think he has not been able to play tournament tennis again, without repaired cartilage.
Of course, I don´t know exactly, but I would like to know more about this.
I am skeptic about new and of course expensive therapies, too, but I think it is not unpossible to find working regenerative stem- cell-therapies, and I hope one day anyone will find the key to this medical future.
Please keep in mind, ACT with Robert Lanza has already shown, that it is possible to do successful medical applications at the eyes with stem cell treatments.
But… and it’s a big, big but… Lanza has TWO published papers in the Lancet supporting those stem cell-based treatments. The biggest reason for me to be skeptical about the Gordie Howe story is that there is absolutely no published research from what I can tell. Publication in a major medical journal has to be the gold standard. While it never guarantees anything either, it absolutely has to be where we find the basis for the science.
This review article cites 13 published clinical studies, of which 9 were with MSCs (see Table 1). Functional benefits, if any, appear relatively minor, at least thus far.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212679/
Thank you for your information. I thought/hoped the stem cell miracle would be true, but now I don´t belive it anymore.
But I think the healing of Rafael Nadal could be different. He had to stop tennis for several month, at least he tried a new stem-cell-application.
And now he returned to the center court and is going to play his first match on the 2. of January in Dubai. Because of his injuries it sound to me like a miracle.
I think this is could be a small evidence, that his stem-cell-application is working.
“who heals is right” ?
There are not many details known about his treatment, so it is not used to advertise for someone.
What do you think about Rafael Nadals stem-cell-treatment?
https://www.ipscell.com/2014/11/tennis-star-nadal-to-get-dubious-stem-cell-treatment/
can optic nerve neuropathy be helped?
I am also a skeptic of what is being done in these clinics. But at least with BM-MSCs, ASCs, etc., I can say as someone who works with MSCs that I think that the idea is not that they engraft and differentiate for cell replacement (it is highly unlikely that mesenchymal stem cells differentiate to neural lineages) but rather that they secrete molecules that help to ameliorate the lesion environment (e.g., through effects on immunomodulation, gap junctions, growth factors) and possibly recruit/activate endogenous stem cells, and then die relatively quickly. This has been shown fairly extensively in animal models. NSCs have also been shown to mediate effects through factor secretion. Of course, for neurological injury, it then means that such therapies are most likely to be effective in the acute, subacute, and initial secondary injury phases where inflammation is still rampant and the lesion environment can still be modulated to affect outcome. It is unclear how much such approaches could be expected to have benefit in the chronic phase of injury. Regarding graft viability, though, it should be noted that some approaches are being taken to prevent rejection (e.g., cell encapsulation). I am skeptical, though, of how bloodstream injections of stem cells would be effective or would deliver sufficient numbers of cells to the lesion site to actually have an effect.
Shinsakan: Thank you for your insights. I don’t work with MSCs, but from what I’ve read in the literature, they seem to sometimes have modest anti-inflammatory effects and some MSCs and NPCs seem able to be attracted to areas of inflammation.
BUT, there is tremendous variation among the cell preparations – some have effects and others don’t. Some are inert, and some are harmful.
If I were working on MSCs or NPCs, I would focus on identifying the characteristics that might make them useful. Homing behavior could be used for targeted delivery of drugs to areas of inflammation. Identification of exactly what factors they produce could lead to new therapeutic drugs. Some scientists – not enough – are already investigating these ideas.
But randomly injecting cells into people without analysis of the cells, without rationale, and without follow up does not give us any new knowledge.
Wouldn’t it be great if all those unlicensed clinics would agree to send the cells they use to a lab for analysis? And report follow up studies on their clients? If so, the money spent by desperate people would not be completely wasted.
Dr. Loring,
I totally agree with you.
When I was working with MSCs, we observed better than modest anti-inflammatory effects, but we were implanting them directly into the lesion site (in a rat model) and also engrafted into a biomaterial scaffold designed to enhance their capabilities while increasing viability after transplantation. We were also interested in isolating particularly useful subpopulations and evaluating specific factors and mechanisms involved in the effects, and other members of the lab were investigating the mechanisms of homing behavior to more effectively utilize it.
Nonscientific work on MSCs and random transplantation of an inconsistent product as you mentioned reduces the credibility of those doing legitimate work in the field.
I hope, too, they will answer these questions, soon. It sounds like a breakthrough, which could give hope to so many people. But why don`t they explain the details of this medical application ?
I wish I could simply take all of this at face value, but as of right now, I think that people are justified in withholding too much enthusiasm. Emotional, subjective reports from relatives are not enough (yes, even when those relatives are themselves medical doctors.) That interview was full of emotional-language red flags such as this one:
Below is the complete text of Murray Howe’s Thursday email defending his father’s stem cell treatment:
“I’ve read with great interest the blogs from a handful of skeptics in the stem cell research community. I fully understand their skepticism and questions raised. I am well-positioned to respond. If I did not witness my father’s astonishing response, I would not have believed it myself.”
“I watched as he rattled off the names of objects as the speech therapist tested him after the treatment. The therapist’s words were: “This is amazing!” His astonishing recovery was witnessed by a physiatrist M.D., a nurse, and the objective measurements of a physical therapist, occupational therapist, and a speech therapist. In addition, my brothers, sister, and I witnessed it with our own eyes. I’ve got the videos to prove it as well. But if you cannot accept the reports from that many witnesses, you might not believe the video footage. I understand.
”
It goes on and on in this vein. The major question this raises for me is: if the evidence is so unequivocal, then why does his son find it necessary to take such a defensive tone? (The San Diego paper itself refers to what he’s doing as “defending” the treatment.) Why refer to the statements of people who are raising reasonable questions as “blogs from a handful of skeptics in the stem cell research community”? Anyone who’s ever spent any amount of time on pretty much any net forum knows very well indeed that “I read with great interest” is code language for “I’m going to completely dismiss everything you wrote or said, but I’m going to sound restrained in my response.” (I’ve actually been writing about the “read with great interest” phenomenon for years in the context of online social communication.) Why rattle off the list of all the professionals who treated Howe when we don’t have official, on the record statements from any of these people? Why take such a sarcastic tone in addressing the “you” he’s talking about or to (couldn’t exactly figure that one out)?
It’s very possible that the “miraculous cure” may turn out to be true. Howe’s son may just be one of those people who doesn’t realize how he’s coming off; it really may not have dawned on him that his statements would sound so much more rational and helpful if all of the emotional, defensive, sarcastic-sounding content was taken out. But there are just so many red flags. Where are the published studies supporting this treatment? Who approved it in the first place? If it’s so great, then why haven’t there been any U.S. studies? And why don’t we have official statements from all of the medical professionals that are mentioned? Again… I hope this turns out to be the real thing, but there are just too many questions right now.
A follow up article supports the case that Gordie Howe has improved markedly – http://www.utsandiego.com/news/2014/dec/25/gordie-howe-stem-cell-stemedica-novastem-hockey/4/?#article-copy
Just take a look at this article about a sucessful similar medical application:
http://www.dailymail.co.uk/health/article-2719973/Hope-stroke-victims-pioneering-stem-cell-treatment-enables-patients-talk-again.html
Hopefully this therapy is going to be a breakthrough. .
It’s worth looking at this blog post about Stemedica again: http://sctmonitor.blogspot.mx/2012/05/stemedica-thrives-on-neglect.html
Paul (and Kevin at CIRM): let us know if you hear from Stemedica’s lawyers- the company’s very sensitive to criticism (for some reason!)
There’s a nice look at the players and “clinical trial” aspect of this in this at sciencebasedmedicine.org. Needless to say, he’s fairly cynical. He also pings back to this article, btw.
http://www.sciencebasedmedicine.org/stem-cells-versus-gordie-howes-stroke/
Interesting, although he seems to lack an understanding of adult stem cell biology; unlike ESCs, the point is not to get them to differentiate to replace lost cells; the point is for them to secrete factors and exert physical effects that modulate the lesion environment.
Its very possible that allogeneic MSC’s could help, but I think Gordie’s treatment was outside the window of meaningful intervention. Meaning, he got the treatment so long after he had the stroke that it was too late for them to make a difference. Had he gotten the treatment within 24-36 hours after the ischemic event, I would have an easier time believing these reports.
One company doing a very legit study similar to the scenario I described is a company named Athersys. I believe they have P2 results from that study coming out pretty soon. I strongly believe they will be positive.
I think it is not impossible, that a cell therapy will work even later. Of course a fast therapy would be better, but maybe it is going to work later, too.
Hi Paul, Did you try and reach out to the Stemedica and seek answers to your questions? Additional questions, what was the source of these cells? Were the cells autologous or allogeneic? Where they expanded?
Thanks for the comment, Ray. Yes, I did email Stemedica with questions yesterday. I just now got a response now after my post went up and I’m thinking it through. I will post it later.
I’m not sure about the cell type, potential manipulations, etc. Good questions.
What is interesting is that they claim they used neural stem cells along the MSCs. Not the typical SVF clinic operating in the U.S.
Here is a link that may provide detail on teh procedure done on Gordie Howe…
http://www.stemedica.com/info/allogeneic-adult-stem-cells/patents/2014-10-01-Stemedica-Secures-US-Patent-to-Use-Multiple-Stem-Cell-Lines-Simultaneously-to-Treat-Ischemic-Stroke.asp
Interesting. From the patent, it looks like NSCs from the forebrain of an 8-10 week-old fetus together with adult BMSCs, where both cell types are exposed to reduced oxygen tension before transplantation.
Hi Paul, with each new story on Gordie Howe, at some point you need to acknowledge that he has gotten better. after his treatment. That’s not to say that this is a double blinded, placebo controlled study but, based on the continuing flow of information from the family, HE IS BETTER and that is great news.
Hi Ray,
Well, media reports suggest he’s doing better. It’s probably accurate and I hope he is. I wish him the best.
Let’s assume he is doing a lot better that doesn’t mean this is due to his stem cell transplant.To be sure about that we need rigorous, impartial research. For example, he was terribly dehydrated at one point and got rehydration that made him feel better even before his transplant of stem cells. Thanks for your comment. Paul
I agree with you that one patient does not prove anything. On the other hand, we must also acknowledge that this therapy might have significantly helped Mr. Howe even if we don’t know which set of stem cells provided the most help. Soon, we will have Phase II, double blinded, placebo controlled stroke data from Athersys using their allogeneic therapy called Multi-Stem: http://www.athersys.com/releasedetail.cfm?ReleaseID=888959 One of the primary MOAs is mitigating the spleen’s over inflammatory reaction to the infarct within the first couple of days following a stroke. As a result, it has little to do with Gordie’s treatment. However, unlike the single case of Mr. Howe, success would put the entire regmed movement on the front page as the ramifications would be immense.