√ Why I Am Still Very Skeptical About Stem Cells For Autism

When patient families reach out to me, one of the most common questions is whether stem cells for autism offer real hope.

The short answer at this time remains “no”. Of course, it’s not as simple as just “no” because there isn’t enough data to be sure, but there is reason for major skepticism about the use of stem cells for autism.

I’ve covered this topic a number of times over the years because patients and families want to know and because it is so often hyped. Sure, there are real clinical trials now and then with FDA approval to test stem cells in autistic patients, and in theory some may ultimately prove to be safe and effective. However, of those recently and currently being tested as well as other “therapies” already being sold at dubious clinics, I doubt any will make it to the finish line as making a real difference.

Why am I so skeptical still? Many reasons.

• There is no compelling, preclinical evidence that I know of that stem cells can help autism and that they would be definitely safe in kids.


• The most common route of administration, IV into the blood stream, doesn’t make much sense to me. Do a meaningful number of cells even get into the brain that way?


• If cells don’t get into the brain, they do something systemically that helps the autistic brain? Some folks believe that there is a definite autoimmune component to autism and that flooding the bloodstream with stem cells might reduce autoimmunity, but there’s little hard evidence for either of these ideas.


• If yes they do get into the brain, what do the cells that get into the brain do that is helpful and where do they do it inside the brain? Which brings me to the next question.


• What causes autism spectrum disorder? The field doesn’t really know so how can you treat it if you don’t understand it?


• Under that umbrella “spectrum” term there are many manifestations and probably many causes so stem cells are unlikely to be an autism panacea.


• Is there any evidence that once autism manifests that it is reversible?

And the list of concerns and questions goes on and on…

According to clinical trials.gov, there are now 13 studies across the globe and 4 registered stem cells for autism trials in the US (see map above). The one here in California at Sutter has ended and no data are posted or published that I know of at this point. The one listing in Arizona and two in Virginia as well as one of the two in Florida (really apparently four that are just one study together) are also completed. They were kind of different in that they was based on the idea that hyperbaric therapy would help boost stem cells in kids with autism. No data posted. The other one in Florida, with Ageless Regenerative Institute as sponsor, was withdrawn. There the notion was to use fat stem cells to treat autism. I have no idea how fat stem cells could by any stretch of the imagination help autism. Unfortunately quite a few stem cell clinics sell stem cells of autism, which is deeply concerning. It is experimenting on kids for profit with little chance of success.

My clinicaltrials.gov search did not find the specific stem cells for autism trial most in the news of late, the one at Duke by stem cell scholar Joanne Kurtzberg, because “stem cells” are not mentioned in the listing, just umbilical cord blood. Update: They’ve published their findings here, which supports safety but we can’t be sure about efficacy in this open-label, uncontrolled study (HT: commenter Matt). I’ve posted about Dr. Kurtzberg’s trial and did an interview with her (see pieces here) in the past. To specifically read my older two-part interview with Kurtzberg see here and here.

More broadly there are 24 research articles in PubMed with both “stem cells” and “autism” in the title. Some of this is very interesting research, but it is concerning to see that in this PubMed search as of today at least, the very first result on PubMed is a “trial” in India of infusing autistic children with apparently undifferentiated human embryonic stem cells, which in my opinion is extremely dangerous.

Overall, it’s just not adding up to me that this is a fruitful line of clinical research at this point. I hope I’m wrong. Some may say to me, “What’s the harm in trying?” and I’d say that there are risks of various kinds to the children including health-wise (although these may be relatively lower with cord blood products) and in raising parents’ hopes with little to back it up.

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√ Cord Blood For Cerebral Palsy: Mostly Discouraging New Trial Data

Cropped Flickr image labeled for reuse of cord blood unit

Some notable newly published Phase II data from the Duke cord blood for cerebral palsy trial unfortunately doesn’t give much reason for optimism that this approach is going to have a substantial positive effect for these kids.

The double-blinded, placebo-controlled study did not find a meaningful benefit overall from infusions of autologous cord blood (ACB) for children with cerebral palsy. It didn’t meet its primary endpoint. The study was published in Stem Cells Translational Medicine and was entitled, “Effect of Autologous Cord Blood Infusion on Motor Function and Brain Connectivity in Young Children with Cerebral Palsy: A Randomized, Placebo-Controlled Trial.”

This finding is discouraging overall. I can’t say I’m too surprised as to me at least there is no obvious mechanism by which this would work. Yes, investigational therapies based on non-obvious hypothesized mechanisms can rarely give surprisingly good outcomes anyway, but with the publication of the new data in this case that future possibility seems pretty remote at this point.

Figure 2A, Sun, et al. Stem Cells Translational Medicine

Some hold onto a bit of hope from specific aspects of the new study data because the higher dose (>=20 million ACB/kg) produced some moderate significantly different (better) outcomes than either lower dose or placebo. I feel mostly skeptical about that. I’m no expert on ACB or on cerebral palsy, but I’m looking at the data as a stem cell scientist just based on common sense.

I also found it discouraging that for some key measures the lower dose of ACB may have made patients slightly worse off than placebo, although I’m not sure that change downward was meaningful (see Figure 2A at right, potential low-dose worsening more evident in panels 2B-D). I don’t see significant safety issues based on that and overall this kind of therapy when provided by a proper clinical trial appears safe. Longer term follow up is needed as well.

The authors, including senior author Joanne Kurtzberg and first-author Jessica Sun, focused on the hopeful dosing effect, but more data would be needed to make clear meaning of that. The phase II trial had some limitations too pointed out by the authors that may have impacted the findings including patient family socioeconomic factors and in turn patients receive other kinds of therapies concurrently.

Overall, there just isn’t much evidence to date that stem cells or related cellular therapies can benefit specific pediatric brain conditions examined so far such as cerebral palsy and autism (see recent post on autism including regarding another ACB Duke trial).

I find the mostly discouraging data to be frustrating as pediatric regenerative medicine is an area of research interest for me more broadly and was hoping for better news. There is still reason for hope in general. Cord blood won’t solve everything, but it remains a very promising, powerful resource. We just need to learn where and how it can be best used beyond current indications. Along the way there are going to be both successes and not so great outcomes too, which is a natural progression with clinical science even if it can be discouraging at times.

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√ Deconstructing Infomercial-Like Joe Rogan Stem Cell Video With Mel Gibson

What do you get when celebrity podcaster Joe Rogan talks about stem cells? There can be big impact one way or another.

Patients can be strongly influenced by what they see on social media and YouTube videos pack a strong punch so maybe once every few years I look on YouTube to see what’s up there for stem cells as I did in 2015. Now, in July 2018 the top video I see for such a search is one in which Joe Rogan chats with Mel Gibson and stem cell provider Neil Riordan. You can see the video below.

Remarkably, this video has about 1.8 million views and thousands of comments. Those may be records for a stem cell-related video.

I watched most of this video over a period of a few weeks as I had a few minutes to spare here and there. For the average person who doesn’t know a whole lot about stem cells or biomedical science, I can see how it’d be convincing. But at its heart it seems to me as a stem cell biologist that the video functions as a stem cell infomercial for Riordan and his institute.

What’s the deal here?

Riordan is a PhD who is the leader of the Stem Cell Institute in Panama, which has marketed a variety of stem cell offerings over the years. Now his focus appears to be on umbilical cord stem cells, which it seems his institution amplifies in culture prior to use.

There is promise to these cells more generally, but they aren’t going to be a panacea. Even in very narrow areas of carefully controlled clinical study, results have been generally mixed at best. For instance, rigorous trial work at Duke studying somewhat similar cells has so far been frustratingly underwhelming as to efficacy.

Also, keep in mind these are allogeneic cells that don’t stick around much in the body, which Riordan acknowledges. How they would be helpful across the aging body or in autistic kids or in other patients is unclear. Big, long-lasting benefits seem almost impossible even from a common sense perspective.

So what’s this video like?

In it Rogan is very upbeat about stem cells and doesn’t probe much as an interviewer. He also mentions his own perceived positive experiences with stem cells. To me he seems too cheery about stem cells, and I’m a big fan of stem cells.

Gibson talks about how he believes stem cells from Riordan were transformative for his elderly father. When Gibson talks about his dad, it is powerful, but that doesn’t mean this stuff really works. Gibson has also himself gotten stem cells.

Riordan makes a number of medical claims about what his institution can achieve with stem cells for a whole rainbow of conditions. It is mentioned that there are published papers on this specific stuff, but from what I’ve seen there isn’t much scientific rigor there in my opinion. Mostly we hear very big, unsupported claims about outsized positive outcomes for almost any medical problem. Does it sound too good to be true? I’m highly skeptical of the safe and effective use of these cells at this time in aging and especially in autism. Injecting laboratory-cultured stem cells into kids also invokes more bioethical considerations and there could be unique long-term risks that we do not understand.

Overall, to me this video again feels like an informercial that has likely greatly benefited Riordan.

I wonder if Joe Rogan would have an academic stem cell scientist on his show? Would he be much tougher on them? Even so, it may be worth it to provide more balance and facts regarding stem cells to a wider community.

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√ Stem Cells For Autism: Time To Hit Pause In 2018?

Stem cells for autism?

After watching this area for many years, I’m not sure there’s any “there there”.

There are logical reasons to think that certain stem cells might help many specific diseases, but in my view autism isn’t likely to be one of them. I hope I’m wrong, but today at least in 2018, it’s not looking promising.

To be clear, I’m not talking about indirectly using stem cells for non-clinical trial research to provide conceptual and translational insights into autism spectrum disorder, which makes very good sense (e.g. see this paper studying autism using IPS cells and a figure from it, which showed changes in neural cell properties using IPS cells derived from autistic patients as compared to controls), but rather my concern is over transplanting stem cells into autistic patients with some expectation of benefit.

Marchetto, et al. figure panel

There is no concrete, common sense connection between autism and any stem cell treatment that I can think of, but others have speculated on possible roles that infusions of stem cells could have in being helpful. Yes, something doesn’t necessarily have to make sense to work in science or medicine, but common sense sure is the best place to start an experiment.

Conversely, the lack of a solid, logical foundation is always going to be worrisome, especially when experimenting with children as the research subjects.

Since I last did a piece on autism in 2017, a couple new studies have come out but they don’t give much reason for enthusiasm on the idea of stem cells for autism. Why am I still so skeptical? I can’t articulate it much better than this list of concerns and open questions I had last year:

• “There is no compelling, preclinical evidence that I know of that stem cells can help autism and that they would be definitely safe in kids.


• The most common route of administration, IV into the blood stream, doesn’t make much sense to me. Do a meaningful number of cells even get into the brain that way?


• If cells don’t get into the brain, they do something systemically that helps the autistic brain? Some folks believe that there is a definite autoimmune component to autism and that flooding the bloodstream with stem cells might reduce autoimmunity, but there’s little hard evidence for either of these ideas.


• If yes they do get into the brain, what do the cells that get into the brain do that is helpful and where do they do it inside the brain? Which brings me to the next question.


• What causes autism spectrum disorder? The field doesn’t really know so how can you treat it if you don’t understand it?


• Under that umbrella “spectrum” term there are many manifestations and probably many causes so stem cells are unlikely to be an autism panacea.


• Is there any evidence that once autism manifests that it is reversible?”

I don’t really see any new data to challenge these points or answers the questions now versus a year ago.

A central issue worth reiterating is that the causes of autism aren’t well understood so why throw stem cells at it? There are so many proposed causes of autism (and forms of autism) including some listed here at Autism Speaks and many more ideas that can easily be found on the web, but the fact is that even the top experts don’t know definite etiologies. Without better understanding of the causes of various forms of autism, things like stem cell transplants are really shots in the dark at best.

In terms of cell types, the most common focus in this area is on using umbilical cord blood or umbilical cord stem cells to try to help the symptoms of autistic children, but certain for-profits will inject just about any kind of stem cells to “treat” autism for cash.

Of course, some excellent scientists are doing real clinical trials with good intentions and again a couple new papers have reported study results. Most recently, a study in part based here in Sacramento that I covered at its start 6 years ago, reported no statistically significant positive effects from stem cells in autistic kids. This pioneering study was just recently published in Stem Cells Translational Medicine and was entitled, “Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism.” As a randomized, placebo-controlled, blinded study, it had a much more rigorous design than other studies that by contrast lacked controls and blinding. From the paper:

“There were also no statistically significant differences between scores on the two primary or secondary endpoints after infusion with AUCB versus infusion of placebo.”

The other study that comes to mind is the Duke, open-label, uncontrolled trial by Joanne Kurtzberg and Geraldine Dawson using umbilical cord blood published last year and now with a secondary follow up paper recently this year. The trial does not have the design (again not blinded, no controls, etc.) nor power to make clear conclusions about efficacy. Therefore, I’m concerned when I see it portrayed as indicating that umbilical cord blood helped the kids who were participants. For instance, this quote in a newspaper piece raises questions:

“And we found that about 70 percent of the children improved getting their own cord blood,” said Kurtzberg.”

This statements sounds very definitive, but are there solid data there to back up such a claim? The authors themselves wrote in their paper something that instead sounds much more neutral:

“As an uncontrolled open‐label study, it is not possible to determine whether the observed behavioral changes were due to the treatment or reflect the natural course of development during the preschool period.”

Maybe they have rigorous data that is unpublished to back up the 70% claim? 

For background you can see some of my past posts on the Duke work and other posts that at least mention it here. More specifically you can see that I was pretty skeptical 4 years ago as this study was launched and again I don’t feel any more encouraged today.

At that time, Arnold Kriegstein, Director of UCSF’s Broad Center of Regenerative Medicine and Stem Cell Research, was highly skeptical too and this quote from him hit on specific issues related to the seemingly weak rationale for this and other similar studies that still resonates today:

“These are not cells that can treat a laundry list of diseases,” he says. Because the stem cells are similar to those that normally give rise to blood cells, he says, it is unlikely that they can repair or replace neurons in the brain. Also, because autism results from errors during development, it is unlikely that the stem cells can reverse those effects.”

Another concern about the whole notion of stem cells for autism is that it indirectly helps to fuel aspects of the unproven stem cell clinic industry both here in the U.S. and in other countries, such as Panama. For-profit clinics selling stem cells for autism do a great job marketing in many ways and sometimes play off of the discussion of results from studies at universities portrayed as encouraging in the media.

While the university/medical center studies mentioned in this post have generally reported a good safety profile for umbilical cord blood for autistic patients, there are always going to be some risks. Certainly some of the stem cell clinics increase the risks with their practices including sometimes not using proper lab technique and also growing the cells in culture prior to transplantation. Furthermore, the fact is that although stem cells used in the two actual clinical trials mentioned here had solid safety profiles so far, longer term we just don’t know if there could be unanticipated risks for these kids.

More trial work specifically on stem cell infusions or similar types of transplants for autism will surely continue, but given all of this, it’s reasonable to ask, “should it?” I realize patients and families are looking for hope (I get many emails from parents), but is this a direction still worth pursuing with limited resources and energy or is it time to hit the pause button?

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