The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages
Authors: James Jeffrey Bradstreet
Nicola Antonucci
Dario Siniscalco
Alessandra Cirillo
Journal: Journal of Neuroinflammation (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Immune system dysregulation; autism; endocannabinoid system; cannabinoid receptor type 2 (CB2R); Gc protein-derived Macrophage Activating Factor (GcMAF)
Affiliations: Department of Experimental Medicine, Second University of Naples, via S, Maria di Costantinopoli, 16 - 80138 Naples, Italy. .

Abstract:  Background: Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder. The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls. Methods: To achieve these goals, we used biomolecular, biochemical and immunocytochemical methods. Results: GcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children. Conclusions: This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism. 

Retracted: No

PubPeer comments:
  We thank David Noakes and Immuno Biotech - St. Peter Port, Guernsey, for providing GcMAF. David Noakes was subsequently convicted and imprisoned in the UK for producing a substance that he claimed was GcMAF, under conditions that had not been certified as suitable for human medicines, and marketing it with medicinal claims. He was then extradited to France to face further charges related to his GcMAF business. Here the authors boast of administering Noakes illegal nostrum to children. Author Bradstreet subsequently shot himself after the FBI approached him with questions about his involvement in the GcMAF racket. In retrospect, do the surviving authors accept that they were accomplices in Noakes criminal activities? , 
 - 17. **Yamamoto N**, Naraparaju VR. Immunotherapy of BALB c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor. Cancer Res. 1997;57(11):2187u20132192. - 18. **Yamamoto N**, Naraparaju VR, Moore M, Brent LH. Deglycosylation of serum vitamin D3-binding protein by alpha-N-acetylgalactosaminidase detected in the plasma of patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1997;82(3):290u2013298. doi: 10.1006 clin.1996.4320. - 41. **Yamamoto N**, Willett NP, Lindsay DD. Participation of serum proteins in the inflammation-primed activation of macrophages. Inflammation. 1994;18(3):311u2013322. doi: 10.1007 BF01534272. - 43. **Yamamoto N**, Suyama H, Yamamoto N. Immunotherapy for prostate cancer with Gcprotein-derived Macrophage-Activating Factor. GcMAF TranslOncol. 2008;1(2):65u201372. - 44. Kanda S, Mochizuki Y, Miyata Y, Kanetake H, **Yamamoto N**. Effects of vitamin D (3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis. J Natl Cancer Inst. 2002;94(17):1311u20131319. doi: 10.1093 jnci 94.17.1311. These are a lot of citations for an author who lost three GcMAF clinical studies to retraction, on account of the absence of records to show that patients had provided informed consent, or indeed existed at all. , 
  16. Bradstreet JJ, Vogelaar E, Thyer L. Initial observations of elevated alpha-N-acetylgalactosaminidase activity associated with autism and observed reductions from Gcprotein-Macrophage Activating Factor injections. Autism Insights. 2012;4:31u201338. Do the surviving authors still regard this paper as dispositive?  [I do not think it is unreasonable to describe Autism Insights as a vanity journal] . After accepting a few more papers (including the present topic), the publisher lost interest or the funding stopped and it disappeared, leaving only the incomplete archive at CLOCKSS.  Turning to the present paper, the third author is currently in French custody awaiting trial on charges of manufacturing and distributing and making false medicinal claims for an unlicensed and indeed discredited product, the  GC Proteinu2014Macrophage Activating Factor Injections of the title. The first author is dead, having committed suicide when the FBI started asking questions about GcMAF and fraudulent practices. The second author was found guilty of medical fraud, i.e. billing health insurers for unrequested and meaningless blood tests, though I understand that his fine was reduced on appeal. , 
 #1 You should carefully read the article before writing. We did not treat childrens. We studied the effect of the molecule in laboratory on in vitro cellular system. We did not have any relationship with Noakes. Your sentence is offensive for us, and the entire your comments are not scientific ones. We are wondering if this blog is scientific or gossip one. ,