Friday, 23 May 2014

GcMAF and autism continued

"GcMAF treatment was able to normalize the observed differences in the dysregulated gene expression of the endocannabinoid system of the autism group". That is the potentially very important finding from Dario Siniscalco and colleagues* (open-access here) continuing the increasing scientific interest in all-things GcMAF (Gc Macrophage Activating Factor) with autism in mind.
Watson and the shark @ Wikipedia 

A quick recap first: I've talked GcMAF and autism on this blog before (see here and see here) and how activating the 'big eaters' (macrophages) of the immune system might be important for some autism and a variety of other conditions too. The collected literature on GcMAF and autism is small... very small... at the moment comprising one paper by Bradstreet and colleagues [2]. So it is indeed a welcome sight to see some more science being done on this area (with the promise of more to come).

The recent paper by Siniscalco et al is open-access but a few pointers might be useful:

  • Blood samples were provided by a small group of participants diagnosed with autism (n=22) and age- and sex-matched asymptomatic controls (n=20). Blood monocyte-derived macrophages (BMDMs) were derived from said samples and dosed with GcMAF.
  • At the same time, building on previous work by the authors [3] suggesting involvement of the cannabinoid system (EC) in some cases of autism, authors sought to examine whether the therapeutic effects of GcMAF previously highlighted in autism, might have something to do with the regulation of genes involved with the cannabinoid system. To look at this question, they extracted RNA from the BMDMs to look at the effect of GcMAF on the "transciptional regulation of EC genes". Those genes included CB2R, FAAH, NAPE-PLD and GAPDH.
  • The results: quite a few of them but they included: "GcMAF treatment was able to significantly increase gene expressions both NAPE-PLD... and FAAH" in BMDMs from participants with autism. This contrasted with no observed changes in gene expression of any of the EC genes in the control samples.
  • Perhaps a little unusually given the meaning of the name GcMAF as a 'macrophage activating factor', "GcMAF was able to trigger overall macrophage deactivation in autistic samples". Based on looking at something called Ki67 involved in cell proliferation, authors reported "a decrease of 23% in GcMAF treated monocyte derived macrophages from autistic children as compared to untreated macrophage cells". This reduction was also noted in the control samples too.

I don't mind telling you that I kinda reached the limits of my very rudimentary knowledge of GcMAF and autism with this paper. I do find that the possibility of involvement of the cannabinoid system to cases of autism to be something really rather interesting as per other results in this area [3] and related research including that potentially impacting on comorbidity such as epilepsy. Linking GcMAF to that system potentially opens up some interesting research avenues.

The fact also that GcMAF seemed to have a deactivating effect on macrophages is also a point of interest. I hope I'm not mis-interpreting the findings or anything but I do wonder if this would reinforce the fact that other biological effects may need further analysis when it comes to GcMAF and autism. It's also interesting that nagalase activity was not discussed in the Siniscalco paper so perhaps further inspection of those EC genes and their expression with nagalase in mind should be indicated in future work too.

And if you want the authors take on this work, look no further...

Here's a little song for everyone out there.... so said Kiss. And the rest is rock history.


[1] Siniscalco D. et al. The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages. J Neuroinflammation. 2014 Apr 17;11(1):78.

[2] Bradstreet JJ. et al. Initial observations of elevated alpha-N-acetylgalactosaminidase activity associated with autism and observed reductions from GC protein—macrophage activating factor injections. Autism Insights. 2012. 4: 31-38.

[3] Kerr DM. et al. Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behav Brain Res. 2013 Jul 15;249:124-32.

---------- Siniscalco D, Bradstreet JJ, Cirillo A, & Antonucci N (2014). The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages. Journal of neuroinflammation, 11 (1) PMID: 24739187