Saturday, 11 October 2014

Efficacy of foetal stem cell transplantation in autism...

The recent news that researchers might be one step closer to 'curing' type 1 diabetes following the publication of the paper by Pagliuca and colleagues [1] brought back into focus how stem cell therapy might hold some promise for all manner of conditions. The idea that researchers could generate "hundreds of millions of glucose-responsive β cells from hPSC [human pluripotent stem cellsin vitro" still faces a few challenges, including overcoming the immune assault central to the autoimmune condition that is type 1 diabetes. I have but one comment to make about the immune system and autoimmunity in this context: worm pills (see here)...

The question of whether an advance has been similarly made following the publication of the paper by Jeff Bradstreet and colleagues [2] (open-access available here) is perhaps open to some discussion with their observations that: "Statistically significant differences (p<0.05) were shown on ATEC/ABC scores for the domains of speech, sociability, sensory and overall health, as well as reductions in the total scores when compared to pre-treatment values" based on the use of foetal stem cells (FSCs) "in treating children diagnosed with ASDs [autism spectrum disorders]". Further details about the study can also be found in the latter slides of the presentation shown here.

Stem cell therapy in the context of autism is still a scientific hot potato. I've covered previous, very preliminary, forays into this research area before on this blog (see here). It is with the same cautions and caveats that I discuss the latest paper from Bradstreet et al.

So:

  • This was a study of some 45 children diagnosed with an autism spectrum disorder (ASD) (mean age = 6-7 years). Diagnosis was confirmed by some of the gold-standard assessment instruments including ADOS and ADI. There were quite a few exclusion criteria applied to study entrants such that those with epilepsy, or "a neurological or co-morbid psychiatric disorder" were not examined. Learning disability without autism was also "considered exclusion criteria" as was a diagnosis of Asperger syndrome.
  • The study was based in Kiev in the Ukraine where "stem cells harvested from 5-9 weeks old human fetuses following voluntarily – elective pregnancy terminations (legally available in the Ukraine)" were used. I don't doubt that there may be some who have strong views about this practice as per commentary from other authors (see here). Hematopoietic stem cells (HSCs) after harvesting were tested for various bacterial, fungal and viral infections as were the women who previously carried.
  • Long quote coming up... "Stem cell transplantation of suspensions containing cryopreserved fetal stem cells were preceded by pre-medication of the subject via intravenous slow infusion of diphenylhydramine (Darnitsa, Ukraine) 10 mg and prednisone (Darnitsa, Ukraine) 15 mg on Day 1 and diphenhydramine (Darnitsa, Ukraine) 10 mg on Day 2". At this point, I'll draw your attention to some other work previously discussed on this blog on a possible role for corticosteroid therapy for some types of autism (see here) which included the use of prednisolone, the active metabolite of prednisone. After which the stem cells were administered...
  • Results: "Early post-transplantation effects were reported in 78% of children: 26% of these children became calmer; eye contact was improved in 9%, while 29% had better appetite and 23% had an improved affect". Importantly, the authors report that no adverse effects were initially noted and "No transmittable diseases were noted during the 12 month follow-up". They also make mention of how initial effects may well have been [partly] as a consequence of the corticosteroid and other medication initially administered.
  • Scores on the ATEC and ABC bore out the positive group changes noted between baseline (before stem cell therapy) and at 6 and 12 month follow-up which were also accompanied by various immunological changes "indicative of improved cell-mediated immunity in children".

OK. Despite these results the authors themselves are still cautious about their findings and stress: "future research studies are urgently needed and larger randomized -placebo controlled trials are needed to further characterize potential FSC-associated improvements in ASDs". This was a straight forward observational trial (before and after) which lacked control groups and in particular a placebo-controlled element so one has to be slightly hesitant about the strength of any findings. For those however who might be pulling on this study because of the use of something like the ATEC to measure autistic presentation, I'll draw your attention to some work suggesting that this instrument might be rather useful for monitoring intervention options for autism (see here).

As previously described, feelings run deep about the use or not of stem cells when it comes to autism not least because of the lack of data on long-term safety (and efficacy) in this context, the source 'material' for stem cells and the lack of information on just what might be going on in biological terms consequent to the behavioural results described. Examining this research from a cold, dispassionate, scientific point of view, I have to say that I'm becoming rather interested in what might be potentially going on during this and other studies [3] if not just as a function of other work by the late Paul Patterson and colleagues overlapping with this area [4] (discussed in a previous post). 

That being said, I'd like to see a lot more research done in this area before this kind of intervention enters anything like mainstream autism practice...


----------

[1] Pagliuca FW. et al. Generation of Functional Human Pancreatic β Cells In Vitro. Cell. 2014 Oct 9;159(2):428-439.

[2] Bradstreet JJ. et al. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. Cell Transplant. 2014 Oct 9.

[3] Lv YT. et al. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. J Transl Med. 2013 Aug 27;11:196.

[4] Hsiao EY. et al. Modeling an autism risk factor in mice leads to permanent immune dysregulation. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12776-81.

----------

ResearchBlogging.org Bradstreet JJ, Sych N, Antonucci N, Klunnik M, Ivankova O, Matyashchuk I, Demchuk M, & Siniscalco D (2014). Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. Cell transplantation PMID: 25302490