Fact-checking stem cell therapy for autism: still a risky idea

The other day I gave a talk in part about stem cell hype and mentioned as an example how the idea of already doing stem cell therapy for autism seems so misguided to me now.  On the whole, in my view there are major downsides and risks for autistic kids whose parents are already having them get injected or infused with stem cell-related products.

The goal of today’s post is to explain the concrete reasons why I believe that those promoting cord blood or stem cells for autism are so off-base.  I’m going to write more in the future about stem cells for CP. There are many parallels. I have a video version of this post on YouTube that I’ve included below so please check that out and subscribe to our stem cell channel.

Families should give serious consideration to such concerns before making decisions. Note that I have no conflicts of interest in writing about stem cells or cord blood for autism. My criticisms of those injecting the kids in this area are mainly based on concern for the kids and families involved. I also believe the activities of those experimenting on the kids are generally bad for the stem cell research field.

What’s in this article

Iffy injections by clinics & Duke | Tough questions | Idea of stem cell therapy for autism is flawed | Immune system? | Possible risks | Conflicts of Interest | Looking Ahead | References 

Quick Article Summary and Claim Review. Cord blood and stem cells are an unproven approach to autism and other pediatric neurological conditions. Proponents claim that umbilical cord blood or stem cells can help autistic children and are safe. In my view there are no strong data to support this claim of benefit for autism. The most rigorous study to date by Duke suggests no clear benefit. Other clinical trial data were also negative. As to safety, there are risks too, although cord cells are generally relatively safer than other kinds of cells. The procedures are also expensive. You should consult your child’s pediatrician or pediatric neurologist.

Iffy injections by clinics & Duke

After all these years writing here on The Niche including about unproven stem cell clinics, the most concerning thing for me remains injection of children with unproven stuff like stem cells.

It has crystallized for me in the past half-dozen or so years that one of the main reasons I keep blogging is specifically to try to protect children. Being a professor is such a busy job for me that even spending 3% of my time on outreach like this is a major decision, but I believe it’s worth it. There has been real positive impact I can see over the years even as things have gotten a lot more complicated.

What’s changed over the time that I’ve been writing about autism is that now in addition to sketchy clinics there are also university teams, namely the autism group at Duke University led by Joanne Kurtzberg, operating in this space. It’s very troubling.

To be clear, I’m not talking about indirectly using stem cells for lab research to provide conceptual and translational insights into autism spectrum disorder, which makes very good sense. For example, see this paper studying autism using IPS cells, which showed changes in neural cell properties. They used IPS cells derived from autistic patients as compared to controls.

Rather my concern is over transplanting cord blood or stem cells into autistic patients with some expectation of benefit. Duke and clinics sometimes even require big payments from families.

The data just do not support continuing to do this now. I suppose future data like from Duke’s relatively new cord blood stem cell clinical trial could surprise in a good way with great results. While it’s hypothetically possible, I think that’s a huge long shot and probably not worth the risks and downsides to the children and their families.

Tough open questions that proponents cannot answer

I’ve asked myself and people with autism research expertise some key questions over the years. No one seems to be able to answer these satisfactorily. Without good answers and with discouraging clinical trial data so far, it seems to me to be questionable to be doing more clinical trials. It’s especially questionable to be injecting hundreds or thousands of autistic kids with an unproven product off-study via compassionate use. And to require payment for this.

Here are some examples of these questions with my attempts to either answer them or provide context.

• The most common route of administration of cord cells for autism, IV injection into the bloodstream, doesn’t make much sense to me. Do a meaningful number of cells even get into the brain that way? So far, there aren’t clear data on this, but probably the answer is no. In the early days, the fans of cord cells for autism claimed the cells did get into the brain. Now they aren’t talking about this much or at all.
• If cells don’t get into the brain in meaningful numbers, then you think that they do something systemically that helps the autistic brain? Where’s the good evidence? As best as I can tell as a biomedical researcher, there isn’t any. It’s all just a long-shot idea.
• If instead the IV infused cord cells do get into the brain in large numbers, what do the cells that get there do that is helpful and where exactly do they do it inside the brain? It’s impossible to say. Again, there are no good data. 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? The attempt at an answer of proponents seems to be just oversimplification to focus on hypothetical autoimmune issues (more below). That doesn’t sound like the basis for rigorous clinical science. I’ve written more on possible causes of autism below.
• Is there any evidence that once autism manifests that it is reversible?” Arnold Kriegstein, who happens to be on our Medical Advisory Board here on The Niche was the first one I saw who posed this logical question. The answer is unclear. Some kids do show an improvement in symptoms as they get older, but for unknown reasons.

Core idea of stem cell therapy for autism may be flawed

Overall, there is no concrete, common-sense connection between autism and any stem cell treatment that I can think of. However, others have speculated on possible roles that infusions of stem cells could have in maybe being helpful. To me these don’t make much sense.

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, especially a clinical trial. I’d hope that a good idea based on clear encouraging data is the basis for injection of vast numbers of children. And if your data as you’re going along tend to refute your idea, you stop, right? What if millions of dollars depend on your keeping on going?

Those who promote the idea of cord blood and/or stem cells for autism have coalesced around one main hypothesis.

They argue that stem cells given IV may have an immune effect systemically that helps autism. This idea is very unlikely to be correct based on the data that are out there.

It’s not impossible, but there’s just minimal evidence for this.

Why the immune system?

Also, autism is really “autism spectrum disorders” a group of related conditions with diverse combinations of causes. What this means is that at most a speculated key immune system role in some cases of autism spectrum disorders is at most only present in some kids. In turn, this tells us that injecting a diverse autistic patient population isn’t likely to help most of them.

Only some autistic kids have demonstrable immune system issues and these may be unrelated to their autism. Furthermore, it’s also not even clear that cord blood stem cells could help with immune issues specific to autism, if such issues actually exist in a meaningful way. Cord cells in some contexts may have the ability to reduce immune system hyperactivity, but not necessarily in autistic kids. Even in this one narrow area of medical science related to cord blood cells and immune activity in autism, the data are not convincing.

Duke has claimed that its recent clinical trial (showing no overall benefit of cord blood for autism), actually might have shown a benefit for a subset of kids with less intellectual disability than the others. Even if they are right, does it make sense to pursue autism treatment for the subset of kids who have the least bad cognitive symptoms?

Possible risks including from forced sedation

While infusions of cord cells seem generally fairly safe, there are still risks. Long-term safety study data of this approach specifically in children with neurological disorders are rare.

I also recently learned that it’s not unusual for autistic children going to clinics or even for clinical trials to be sedated in order to make them comply with getting stem cell infusions. This brings its own risks and ethical questions.

A physician reached out some months back about an autistic patient whose family was considering going to a sketchy clinic for some kind of cellular infusion. The boy got the infusion and ended up doing worse afterwards.

The worsening may have been due to the travel involved, the ordeal of the needles/injection(s), having to deal with strange people, etc. Or it could have been the infusion. It’s impossible to tell in such cases.

Conflicts of interest of proponents of stem cell therapy for autism

There are good citizen researchers doing studies of cord cells or specifically stem cells for autism. Some of this work includes clinical trials. However, the top two proponents of stem cells for autism, for-profit stem cell clinics and Duke,  both have financial conflicts of interest that raise serious questions.

Of course, stem cell clinics selling the idea of stem cells for autism have an inherent conflict as their business model’s main goal is profit. The most well-known such clinic is the Stem Cell Institute in Panama.

You might be more surprised though that Duke also has conflicts here. Duke has an autism-related deal with the publicly-traded firm Cryo-Cell worth tens of millions of dollars. If cord blood for autism (or CP or other neurological disorders in kids) does not work out, then both Duke and Cryo-Cell are probably going to lose a ton of money. That possibility has no impact on how Duke makes decisions about this work?

I also have concerns over what I see as reverberations between Duke’s team and the Stem Cell Institute.

Looking ahead on stem cells for autism

As we look to the future, sadly I expect both stem cell clinics and the Duke team to continue. No matter what the data say.  That is unless someone like the FDA steps in or the money runs out.

I’m not a physician and I don’t give medical advice. But when parents of autistic children reach out to me about stem cells, I reply. I try to caution them to ask a lot of questions. Expect common sense answers.  Ask about data. If payment is required, ask why. Experimental therapies should not require payment of fees. Maybe ask some of the questions I listed above nearer to the top of this post too. If the answers are shaky or don’t make sense, more caution is in order.

References

1. Boosted by celebrity endorsements and a controversial research program, clinics are peddling stem cell autism treatments questioned by experts, Tom Porter, Business Insider, January 2021.
2. Experts question rationale for stem cell trial for autism, Hannah Furfaro, Spectrum, July 25, 2019.
3. Should You Bank Your Baby’s Cord Blood?, Dana Najjar, New York Times, December 18, 2020.
4. Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder. Sun JM, Dawson G, Franz L, Howard J, McLaughlin C, Kistler B, Waters-Pick B, Meadows N, Troy J, Kurtzberg J. Stem Cells Transl Med. 2020 Oct;9(10):1137-1146. doi: 10.1002/sctm.19-0434.
5. Stem cells and autism search, PubMed, February 2021.

6. Crowdfunding, stem cell interventions and autism spectrum disorder: comparing campaigns related to an international “stem cell clinic” and US academic medical center, Jeremy Snyder and Leigh Turner, Cytology, March 2021.