If you are a parent of a young child with autism (especially level 2 or 3, requiring significant support), the promise of a cure or even an effective treatment is irresistible. This is exactly why there needs to be science-based regulatory standards – to protect vulnerable patients and their loved-ones. RFK Jr., however, wants to weaken these protections – even removing from the FDA website common-sense warnings for parents who are likely to be exploited (the HHS claims the removal was a routine cleanup of their website, a claim that does not pass the smell test).
We have also been covering dubious stem cell clinics here for two decades – the hype surrounding stem cells is perfect for predatory clinics. Stem cell treatments sound like cutting edge science. There is a lot of legitimate research and advances going on, and some therapies are in late stage clinical trials. Treatments often involve injections or infusions, with all the trappings of modern advanced medicine. And such treatments can cost tens of thousands of dollars. It’s a potential cash cow.
Unproven therapies also benefit from what I consider the weaknesses of “evidence based” medicine. EBM itself has some virtues, but it does not go far enough and relies upon a flawed approach to evidence (hence the need for science-based medicine). In practice this makes it vulnerable to exploitation, and what we see is that almost every dubious treatment calls itself “evidence based”, even when the evidence clearly shows it is ineffective.
What, then, is the science-based assessment of stem cell therapies for autism? First let’s address the plausibility – what are these treatments and how are they supposed to work? Right now the most common stem cell treatment offered for autism is intravenous infusions of cord blood. Sometimes stem cells from the cord blood can be cultured and purified. What do these stem cells do?
It is unclear if there is any significant migration of these stem cells into the brain. If any cells do get into the brain, it has not been established that they do anything there, or that what they do addresses any component of the underlying causes of autism. In the periphery they cannot directly affect brain function, but the speculation is they might reduce autoimmunity, or support mitochondrial function or angiogenesis (increasing blood flow), or perhaps have an anti-oxidant effect.
These speculations are all extremely familiar – they are among the most common hand-wavy explanations for how many dubious treatments are supposed to work. In my opinion, they are essentially worthless, because you can say them about almost anything. They have become almost the equivalent of saying “it’s magic”. Seriously – from a scientific perspective, the justification for IV infusions of stem cells to treat autism is as solid as giving someone a magical elixir in the hopes that it will somehow do something.
I don’t think these putative mechanisms are even enough to justify clinical trials, but we have had some clinical trials anyway. Regular readers here likely suspect what’s coming – a 2022 systematic review and metaanalysis found that:
“The results of this meta-analysis suggested that stem cell therapy for children with autism might be safe and effective. However, the evidence was compromised by the limitations in current study size, lacking standardized injection routes and doses of stem cells, as well as shortages in diagnostic tools and long period follow-up studies. Hence, it calls for more studies to systematically confirm the efficacy and safety of stem cell therapy for children with autism spectrum disorders.”
This is so common it’s a cliche – essentially the studies are all crap, in this case the results are essentially uninterpretable, so we need more studies (do we, really?). Being charitable, what this means is that stem cells for autism should not be offered outside of a regulated clinical trial, patients should not be charged for the treatment, and no clinic should market the treatment with any claims of effectiveness.
But there’s more, because there was further research, and a high quality one at that. Duke Health conducted the best study to date on this treatment, a Phase II study with 180 subjects, placebo controlled and double blind. They used a primary outcome and many secondary outcomes and reasonable follow up. What did the study show – dead negative. Every single outcome measure showed no difference between treatment and control, not even close. No p-values even flirted with significance. It’s as negative a study as you can imagine.
Phase II studies are often used to determine if it is worth proceeding to Phase III studies, the kind needed to get FDA approval. Such a negative study should be the death of this treatment, but the Duke researchers somehow found the results “encouraging”. What? How do they justify that? They conducted a post-hoc analysis and found that if you limited the analysis to just children without intellectual disability there was a trend toward benefit (not even statistical significance). Finding a trend in a post-hoc subgroup analysis is a classic maneuver for trying to rescue something positive from a negative study. It’s essentially nonsense. It would be amazing if you couldn’t find a subgroup with a trend.
It’s understandable that researchers are invested in their treatment working. We would all love to have an effective biological treatment option for ASD. So some motivated reasoning is expected. But there may be another layer here as well. According to MSN:
“More recently, Duke’s partnership with Cryo-Cell International, a company that banks cord cells and licensed Duke’s intellectual property to pursue autism infusion clinics, has collapsed – a signal that even commercial interest in the science has waned.”
If they were also pinning their hopes on a cash cow stem cell clinic, their motivated reasoning becomes more clear.
The best summary of the current situation is that:
- Stem cells for autism do not have a clear or established mechanism of action
- The treatment is expensive and invasive with demonstrable risks, and therefore caution is appropriate
- Existing clinical evidence is a combination of low-quality studies and one high-quality study that is completely negative – most consistent with the conclusion that stem cell infusions are ineffective as a treatment for autism.
- Parents should remain extremely cautious before pursuing such treatments, especially since there are many predatory stem cell clinics out there waiting to take their money. I personally would not recommend the treatment – those health care dollars are better spent on established interventions.
Given all this, I do not think that further clinical research is warranted. If someone believes there is still potential here, then what is required is to do further basic science research to establish a potential mechanism, a way of identifying subjects that might respond, or a method of treatment with a plausible chance of working better than cord blood. In short, clinical research should stop unless or until further basic science research provides a new justification for it.
Further – regulatory agencies like the FDA should crack down on dubious stem cell clinics offering cord blood or similar treatments for autism. They have cracked down in the past, with good results, but when they pause their crackdown, stem cell treatments for autism explode. There is simply too much money to be made here from desperate parents.
Meanwhile, the opposite appears to be happening. RFK feels he has personally benefited from stem cell treatments for his spasmodic dysphonia, and he apparently thinks this is enough justification to make it easier for Americans to get experimental, speculative, and even dubious stem cell treatments without having to travel abroad. Evidence be damned.
