Sunday, 29 March 2015

Sera from children with autism inducing autistic features in rats?

"The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty."

That was one of the findings reported in the paper by Syed Faraz Kazim and colleagues [1] (open-access) who, among other things, injected intracerebroventricularly sera collected from children with autism into newborn rats and examined behavioural effects compared with injections of sera from asymptomatic controls. Actually, that was only one part of the research from Kazim et al but it does invite some further interesting questions...

In brief, and bearing in mind the paper is open-access, a few details:

  • A caveat first: "Based on studies described in this manuscript, the authors submitted a patent application to the United States Patent and Trademark Office on 12/11/2014, entitled: “Treatment of Autism Spectrum Disorders with Ciliary Neurotrophic Factor Peptide Mimetic”; application number US62/083,570; Inventors: Khalid Iqbal and Inge Grundke-Iqbal." The authors report a potential competing interest and good on them for doing so.
  • As noted, there were several aspects to this research focused to a large extent around neurotrophins including something called ciliary neurotrophic factor (CNTF) or rather "a CNTF small peptide mimetic, P6" which might have the ability to increase levels of BDNF (brain derived neurotrophic factor ), a compound that has cropped up before on this blog (see here).
  • So: sera from children with autism were initially added to "mouse primary cultured cortical neurons grown for 72 hours in medium" and resulted in "gross morphological changes". Pretreatment of said mouse neurons with P6 - "which corresponds to amino acid residues 146–156 of human CNTF" - seemed to have an effect that: "resulted in a significant reduction in cell death in cultured neurons treated with sera from autistic children." Another detail derived from this experiment: "Primary cortical neurons grown in the presence of autistic sera showed higher levels of oxidative stress." Interesting in light of other research in this area with autism in mind (see here)...
  • Next: what was it in the sera from autistic children which seemed to be having effects on mouse neurons which weren't seen in control sera? Well it's possible that: "the presence of neurotrophic abnormalities in the sera from autistic children that could have contributed to altered development of neurons and increase in cell death and oxidative stress found." By neurotrophic abnormalities, the authors meant issues with "mature CNTF and BDNF" among other things.
  • Next were the results from those studies where rat pups were injected with autism or control sera "with or without P6". More quotes: "alterations in the levels of neurotrophic factors in the sera from autistic individuals could contribute to neurobehavioral phenotype of autism in rats". By that the authors reported some potential differences in rat behaviour focused on things like grooming behaviour (repetitive behaviour) and ultrasonic calls (akin to social communication). P6 potentially rescuing functions was also reported for some of the tests.
  • Conclusion: with the caveats of much more investigation required and that rats are rats and not humans (see here) "this study provides evidence regarding the neurotrophic abnormalities in autism and the potential role they play in the pathophysiology" of the condition. Further: "Ameliorating the neurotrophic imbalance during early stages of brain development can serve as a potential therapeutic approach for autism. P6 represents a new class of neurotrophic peptide mimetics that has potential therapeutic value for ASD and related conditions."

I'm rather interested in this work and the potential for at least some cases of autism as and when replicative work is undertaken. I note in other patents from this group (see here) the idea that peptides with a neurotrophic link might have some application to "neural pathologies where BDNF levels are dysregulated" is one that has been embraced.

The authors, the late Inge Grundke-Iqbal & Khalid Iqbal, have a pretty impressive peer-reviewed track record based to a large extent on their work on neurodegeneration and "abnormally hyperphosphorylated tau" as the main component of the tangles in Alzheimer's disease. Indeed, these findings have particular relevance recently (see here). Applying their, and their research groups, expertise to autism is most definitely an asset, albeit with the requirement for quite a bit more research in this area.

To close: The Stone Roses - She Bangs the Drums.

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 [1] Kazim SF. et al. Sera from Children with Autism Induce Autistic Features Which Can Be Rescued with a CNTF Small Peptide Mimetic in Rats. PLoS ONE. 2015; 10(3): e0118627.

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ResearchBlogging.org Kazim, S., Cardenas-Aguayo, M., Arif, M., Blanchard, J., Fayyaz, F., Grundke-Iqbal, I., & Iqbal, K. (2015). Sera from Children with Autism Induce Autistic Features Which Can Be Rescued with a CNTF Small Peptide Mimetic in Rats PLOS ONE, 10 (3) DOI: 10.1371/journal.pone.0118627