"a single intravenous infusion of autologous umbilical cord blood" and autism

'Could stem cells offer hope for autism?' went one media headline referencing the very preliminary "phase I, open-label trial" published by Geraldine Dawson and colleagues [1] (open-access) detailing the experiences of a single intravenous infusion of autologous umbilical cord blood in 25 children with "a confirmed diagnosis of ASD [autism spectrum disorder]."

Well, the results were promising in respect of important issues such as safety in light of the tenet 'first do no harm': "Assessment of adverse events across the 12-month period indicated that the treatment was safe and well tolerated" and some potentially interesting effects were noted when it came to behaviour "across a wide range of outcome measures in this study." But much like another quite innovative study with a similar research design published quite recently (see here) one needs to be a little cautious about the limitations of this current study. Not least that: "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." I might add that any study mentioning the words 'stem cells and autism' in the same sentence is going to be subject to significant scrutiny (see here for example).

Although the Dawson paper is open-access, here are a few choice details:

• "All participants had to have an available autologous umbilical cord blood unit banked at a family or public cord blood bank."  This was a study using the participants own stored cord blood - blood 'left over' from the umbilical cord and/or placenta at birth - which was initially screened to make sure it was both viable and safe: "negative maternal infectious disease markers tested on the maternal donor or cord blood product (minimally including hepatitis B, hepatitis C, human immunodeficiency virus [HIV], human T-lymphotrophic virus [HTLV], and syphilis)." Cord blood contains stem cells; cells that have significant [mighty] morphing capabilities in terms of turning into different cell types. In amongst the various peer-reviewed research (and research hype) surrounding stem cells, their use with autism in mind has been slowly creeping into the public consciousness (see here for example) with appropriate caveats.
• Participants were given one infusion of their cord blood samples. They were fairly closely monitored over the study duration to ensure that any adverse effects (AEs) were catalogued. Researchers reported: "A total of 92 AEs were reported in 23 participants... with a median of three events per participant. All events were graded as Mild (71 events) or Moderate (21 events)." Further: "Twelve events (13%) were considered related to the infusion, with the most common being allergic reaction, manifested by urticartia and or/cough occurring on the day of infusion (5 events in 4 participants; all Mild; 2 requiring an additional dose of IV Benadryl). The most common unrelated AEs were agitation, skin changes, and typical childhood infections, reported between 2 days and 1 year post-infusion."
• Alongside looking for AEs, authors also reported some changes to the various behavioural schedules included for study. Looking at scores at baseline (pre-infusion) and then at 6 and 12 months, a pattern started to emerge based on group results. So: "Most of the observed behavioral changes occurred during the first 6 months and were sustained between 6 and 12 months post-infusion." The direction of the behavioural change were all positive (i.e. behavioural measures indicated improvement) and were spread out across both parent-reported and clinician-reported schedules. Interestingly too, eye gaze measurements for some 21 participants who were scanned also showed changes: "a 20% increase in odds of gazing at the actress’ eyes over time." Researchers also noted that: "children's nonverbal IQ was correlated with change for the majority of outcomes measures, with higher nonverbal IQ being associated with greater improvements in behavior." Such a finding might also tie into some other research looking at a group termed 'optimal outcome' (see here).

There is a scheme of research required to follow this preliminary study, of that there is no doubt. We don't for example, know exactly how any behavioural changes were tied into the infusion (or not) because among other things, no other physiological measurements were made over the course of the Dawson study pointing to possible mechanisms. This is not entirely unexpected given the preliminary nature of the study. I will also stress again that these results were based on participants' own stored cord blood samples not other donor samples just in case any incorrect generalisation of results is made. As an aside, I was quite interested to see the use of IV (intravenous) Benadryl in relation to some of those AEs. Benadryl is an antihistamine used to manage allergy symptoms. I've talked before on this blog about how treating allergy issues in relation to some individual cases of autism might have some interesting effects on the presentation of autistic symptoms too (see here). I wonder...

I am assuming that there will be more to talk about in this area of autism research as a consequence of a concluding sentence made by the authors: "we have also included the clinician-rated CGI and additional measures as secondary endpoints in our next study, a phase II, double-blind randomized clinical trial designed to formally evaluate the efficacy of umbilical cord blood infusion in improving core symptoms of ASD." Accepting that there is still some PR to be done with regards to the issue of cord blood and stem cell use in relation to autism [2] (that also includes work related to modelling conditions like autism too [3]), I'll be interested to see whether the current Dawson results survive more rigorous scientific study...

To close, skin problems in Hollywood villains. No really, someone has actually studied this... 

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[1] Dawson G. et al. Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial. Stem Cells Translational Medicine. 2017. April 5.

[2] Sharpe K. et al. In the Know and in the News: How Science and the Media Communicate About Stem Cells, Autism and Cerebral Palsy. Stem Cell Rev. 2016 Feb;12(1):1-7.

[3] Wen Z. Modeling neurodevelopmental and psychiatric diseases with human iPSCs. J Neurosci Res. 2017 May;95(5):1097-1109.

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Geraldine Dawson, Jessica M. Sun, Katherine S. Davlantis, Michael Murias,, Lauren Franz, Jesse Troy, Ryan Simmons, Maura Sabatos-DeVito, Rebecca Durham, & Joanne Kurtzberg (2017). Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial. Stem Cells Translational Medicine : 10.1002/sctm.16-0474