"Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism" safe but...

On a recent visit to the local aquarium with some of my brood, I listened to an interesting talk given by one of the staff. It concerned starfish and, among other things, how these creatures possess the fantastic ability to grow new limbs as and when one or more are 'given' to predators. The mechanism behind such fabulous regenerative power is down to stem cells I was told; those marvels of biological engineering that have the potential to "develop into many different cell types in the body during early life and growth." From what I understand, most, if not all animals have stem cells, although us human folk aren't quite Curt Connors just yet...

Anyhow, stem cells as well as allowing some animals to regrow limbs, have been touted as being potentially *useful* for all manner of other conditions/diseases/ailments (see here). You probably won't be surprised to hear that autism has been mentioned with stem cells in mind (see here for example), with various potential modes of action being discussed. Some of the peer-reviewed research talking about various types of stem cell use in the context of some autism has been quite *hopeful* in terms of observed effects (see here and see here) but not all...

The findings reported by Michael Chez and colleagues [1] (open-access available here) probably fall into that 'but not all' category. Reporting results based on a clinical trial listing (see here), authors concluded that: "autologous umbilical cord infusions are safe for children with ASD [autism spectrum disorder]" but "no statistically significant differences for any endpoints" were detected in their "randomized, blinded, placebo-controlled, crossover trial." I'm not entirely sure therefore as to how at least one press release on the Chez study was able to arrive at some of the text that they did (see here)...

OK, a few descriptions might be useful. Autologous basically means 'obtained from the same individual'. Indeed this was one of the inclusion criteria for the study: "Participants were required to have AUCB [autologous umbilical cord blood] cryopreserved at Cord Blood Registry (CBR, South San Francisco, CA) processed on the AutoXpress (AXP) Platform (Cesca Therapeutics, Rancho Cordova, CA)." That means that stem cell rich blood taken from the umbilical cord that united infant with their placenta had to be available for this study use. The "randomized, blinded, placebo-controlled, crossover trial" bit basically means that this study followed a gold-standard scientific methodology; participants were randomly allocated to receive a cord blood infusion or a placebo, none of the investigators who administered the various tests knew who was receiving which (cord blood or placebo), and at some point in the study, participants switched from cord blood to placebo or vice-versa continuing with the not-knowing status. As for those 'various tests', the primary outcome was scores on the "Expressive One Word Picture Vocabulary Test, 4th edition (EOWPVT-4) and Receptive One Word Picture Vocabulary Test, 4th edition (ROWPVT-4)" alongside some other secondary outcomes looking at behaviour "at baseline 12, and 24 weeks after infusion of each product." Safety of the product was also a key part of this study.

Results: bearing in mind the loss of one participant (to the study results, not anything else!), there are a few noteworthy findings. First, it looks like over the course of the study period at least, this was a fairly safe intervention. Out of a total of 86 adverse events reported, only 3 were eventually thought to be 'probably' related to the autologous umbilical cord blood infusion. Importantly: "No adverse events required treatment" so there is a potential tick for the tenet 'first, do no harm' at least in the short-term. When however it came to looking at those language and behaviour outcomes, the authors note that: "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 authors do talk about "trends in improvement on the Socialization Subscale of the Vineland" but a trend is not the same as a statistically significant result...

The authors opine as to the possible reasons for the lack of statistically significant changes following the use of the cord blood infusion. Dose is mentioned as one possibility, and specifically: "participants varied widely in percentage and number of CD34+ cells in samples infused." Although no expert on CD34+ cells, from what I gather the numbers of these cells present in cord blood samples provides some potential important information on the 'quality' of the infusion as a function of their connection to hematopoietic progenitor cells. The authors also talk about the 'reticence' of parents of participants to "use the entire banked sample on an investigational treatment" given the finite material available.

So, where next for stem cells 'for autism'? Well, given the data showing such an intervention to be safe at least in the short-term, this research area is still ripe for further study alongside chatter about modelling autism via stem cells [2] and beyond [3]. I know there are varied opinions out there about the 'usefulness', long-term safety and acceptability of this class of intervention [4], but like any other area of the autism research landscape, issues such as potential best and non-responders need to be considered before baby and bathwater are thrown out completely...

To close, that (recent) feeling when, at the birthday party of one of your brood, a song by Loded Diper is introduced as the song of the day for the birthday child. Cue the curious looks from other mums and dads and the embarrassed smiles from yours truly...

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[1] Chez M. et al. 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. Stem Cells Transl Med. 2018 Feb 6.

[2] Ilieva M. et al. Psychiatry in a Dish: Stem Cells and Brain Organoids Modeling Autism Spectrum Disorders. Biol Psychiatry. 2017 Nov 16. pii: S0006-3223(17)32197-2.

[3] Donegan JJ. et al. Embryonic stem cell transplants as a therapeutic strategy in a rodent model of autism. Neuropsychopharmacology. 2018. Feb 7.

[4] Simberlund J. et al. Mesenchymal stem cells in autism spectrum and neurodevelopmental disorders: pitfalls and potential promises. World J Biol Psychiatry. 2015 Jul 31:1-8.

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