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What's Holding-Up GcMAF Clinical Trials?
Oct 9, 2012

I've been hearing rumors of an NIH sponsored study of GcMAF in HIV+ patients for many years. Given the below research, can you explain the hold-up? Thank you.

http://www.aidsmap.com/US-research-shows-importance-of-healthy-vitamin-D-levels-for-patients-with-HIV/page/1811989/

The glyco-protein GcMAF (for Group specific component - Macrophage Activating Factor) a.k.a. Dbp-MAF (for Vitamin D binding protein - Macrophage Activating Factor) transports Vitamin D into macrophage cells, making them hundreds of times more active/effective.

But, GcMAF is destroyed by the enzyme alpha-N-acetylgalactosaminidase (Nagalase for short), which is complexed into HIV's gp160 molecules. Nagalase is released from HIV virions as they degrade.

Dr. Nobuto Yamamoto has been studying GcMAF in human disease for about two decades, and has shown that restoring the level of GcMAF in HIV+ patients to that of the general population allowed 39 young, healthy, recently HIV-infected Japanese patients to clear their HIV infections.

A copy of his 2009 paper on the curing of the first 15 patients is available from the publisher for free:

http://onlinelibrary.wiley.com/doi/10.1002/jmv.21376/abstract

Only a short abstract is available, from the 2009 FOCIS Conference, on the second group of 24 patients.

http://www.actions-traitements.org/spip.php?article2905

Only Russia Today dared to bring news of this EARLY treatment cure to light during the 2010 International AIDS Conference:

"Stimulation of immune system heals HIV in weeks" http://www.youtube.com/watch?v=n4eMkdYhaZE

+++++

Nagalase destroys GcMAF, which shuts-down the macrophage cell line, which is considered (one of many) long-lived reservoirs of HIV:

http://www.jleukbio.org/content/80/5/1127.full.pdf

This is "double-jepordy" as macrophage cells are necessary to clear viral infections from ALL reservoirs!

And it has been known for nearly 15 years that viral susceptibility of the macrophage cell line depends on its state of activation:

http://jvi.asm.org/cgi/reprint/71/11/8864.pdf

More on macrophages and their susceptibility to viral infections:

http://www.jstor.org/pss/30105540

"The group-specific component (Gc) system was first described by Hirschfeld (1959), who explained the three patterns seen on immunoelectrophoresis on the basis of two alleles Gc' and Gc2." The United States Public Health Service (USPHS) also supported this early paper on the Group-specific component (Gc) system.

It is suspicious that the USPHS has been supporting research on Group-specific component (Gc) system for nearly five decades, and would have been aware that GcMAF was a cure for early HIV infections nearly ELEVEN YEARS AGO, given its grant to Dr. Nobuto Yamamoro (grant # AI-32140), but does not appear to be working with the NIH/NIAID/DIADS to get a clinical study of GcMAF in early HIV infections started.

Importance of Macrophages in HIV/AIDS Pathogenesis: http://www.ncbi.nlm.nih.gov/pubmed/12103427

Nature Journal article on GcMAF: http://www.nature.com/icb/journal/v76/n3/abs/icb199833a.html

GOOGLE "Therapeutic potential of vitamin D-binding protein" & "Peter T. Gomme and Joseph Bertolini", for their paper at the ScienceDirect.com web site for basic information on GcMAF.

How GcMAF Works - The Video: http://video.google.com/videoplay?docid=2715490034719855134#

June Myung Kim and Sang Moon Han call for a study of GcMAF in HIV-infected individuals in their recent Future Medicine paper:

http://www.futuremedicine.com/doi/abs/10.2217/imt.10.91

Effects of antiretroviral therapy on Vitamin-D deficiency: http://www.ncbi.nlm.nih.gov/pubmed/18928396

Nevirapine does NOT appear to have an effect on Vitamin-D deficiency: http://www.ncbi.nlm.nih.gov/pubmed/19618997

Does Vitamin-D activate HIV? http://www.ncbi.nlm.nih.gov/pubmed/17556530

High frequency of Vitamin-D deficiency in ambulatory HIV patients: http://www.ncbi.nlm.nih.gov/pubmed/19108690

Vitamin-D levels and Immune Reconstitution Inflammatory Syndrome: http://www.ncbi.nlm.nih.gov/pubmed/19383117

Vitamin D status in adolescents and young adults with HIV infection: http://www.ncbi.nlm.nih.gov/pubmed/16685057

A potential role for vitamin D on HIV infection(2006)? http://www.ncbi.nlm.nih.gov/pubmed/16770943 http://www.ncbi.nlm.nih.gov/pubmed/16386106

Now contrast the above with the following three articles...

Efavirenz suppresses Vitamin-D activity: http://www.ncbi.nlm.nih.gov/pubmed/19286836 http://www.ncbi.nlm.nih.gov/pubmed/16954738

Effects of antiretroviral therapy on Vitamin-D deficiency: http://www.ncbi.nlm.nih.gov/pubmed/18928396

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More links:

Dr. Michael Fannon co-authored the below paper which demonstrated the ability of GcMAF to directly kill prostate cancer cells in vitro:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0013428

Dr. Michael Fannon was recently awarded a $363K grant to study GcMAF treatment in a clinical study of prostate cancer patients.

http://healthvv.com/2011/02/02/childrens-hospital-boston-awarded-about-500000-for-prostate-cancer-homework/

----+----|----+----|----+----|----+----|----+----|----+----|----+----|----+----| Microbes Infect. 2005 Apr;7(4):674-81. Epub 2005 Mar 22

Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus.

Yamamoto N, Urade M.

SourceDivision of Molecular Biology and Virology, Socrates Institute for Therapeutic Immunology, 1040 66th Avenue, Philadelphia, PA 19126-3305, USA. uradem@hyo-med.ac.jp

http://www.ncbi.nlm.nih.gov/pubmed/15848273

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The vitamin D axis in the lung: a key role for vitamin D-binding protein http://thorax.bmj.com/content/65/5/456.abstract

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Analysis of the genetic variants of the human Gc system (VDBP) by isoelectric focusing in immobilized pH gradients Prof. Dr. Hartwig Cleve1,*, Walburgis Patutschnick1, Wilhelm Postel2, Johann Weser2, Angelika Grg2 ELECTROPHORESIS Volume 3, Issue 6, pages 342345, February 1982 DOI: 10.1002/elps.1150030609 Copyright © 1982 Verlag Chemie, GmbH

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Yoshihiro Uto, Eiji Nakata, Akina Shibata, Tasuku Akira Tsuji, Hutoshi Susumu Yamamoto and Hitoshi Hori: Design of small molecular GcMAF: GalNAc-lysine derivatives as macrophage activate agents., 130, Annual Meeting of the Pharmaceutical Society of Japan, Mar. 2010

Yoshihiro Uto, Eiji Nakata, and Hitoshi Hori : Design of small molecular GcMAF: GalNAc-lysine derivatives as macrophage activate agents., 130, Mar. 2010.

Yoshihiro Uto, Eiji Nakata, Hideko Nagasawa and Hitoshi Hori: macrophage-activating factor GcMAF sites that mimic the carbohydrate structure of the dendrimer molecular design GalNAc-Thr, 128th Annual Meeting of Pharmaceutical Society of Japan, Mar. 2008.

Hideyuki Sasaki, Hideko Nagasawa, Masayo Kiyokawa, Yoshihiro Uto and Hitoshi Hori: GcMAF precursor activity of human serum Gc study on correlation between the type of treatment for Bio Research Annual Meeting 7th, Dec. 2003.

Department Oyama Yuuzi Scripture beauty Nakagawa, Hitoshi Hori and Tadashi Tadashi Nanba: GcMAF of human monocytes Fc is augmenting significantly the ability to form rosette-mediated receptor-producing ability of superoxide has little effect, Biotherapy, Vol.16, No.1, pp.79--85, 2002.

Saharuddin Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori: Preparation of Gc Protein-derived Macrophage Activating Factor (GcMAF) and, the Fifth Committee on Bio-Treatment, Dec. 2001.

Mohamad Saharuddin, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori: J 774.1 murine cell lines for study GcMAF ability to activate macrophages, the 60th Japanese Cancer Association, Sep. 2001.

S.B. Mohamad, Hitoshi Hori, Hideko Nagasawa, Kenji Usui and Yoshihiro Uto : Characterization of human Gc protein-derived macrophage activation factor (GcMAF) and its functional role in macrophage tumoricidal activity, 29th ISOTT (International Society on Oxygen Transport to Tissue) annual meeting, Philadelphia, PA, USA, Aug. 2001.

Saharuddin Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori: GcMAF and the activation of macrophages in cancer cells derived from HepG2 a-NaGalase effect of cancer therapy sensitizing Research 7th, May 2001.

Saharuddin Mohamad, Hukunaga Akira exhibition, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori: Stimulation of macrophage activity by GcMAF and influence of tumor derived alpha-NaGalase in GcMAF-directed macrophage activation, sensitization Symposium on Cancer Therapy Third International, Feb. 2001.

S.B. Mohamad, Hideko Nagasawa, Yoshihiro Uto and Hitoshi Hori : Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation, ISOTT2000 (International Society on Oxygen Transport to Tissue), Nijmegen, Netherlands, Aug. 2000.

Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation, Comparative Biochemistry and Physiology, Vol.132, No.1, pp.1--8, 2002.

Preparation of Gc Protein-derived macrophage Activation Factor (GcMAF) and its Structural Characterization and Biological Activities., Anticancer Research, Vol.22, No.6C, pp.4297--4300, 2002.

Characterization of Human Gc Protein-derived Macrophage Activation Factor (GcMAF) and Its Functional Role in Macrophage Tumorcidal Activity, Advances in Experimental Medicine and Biology, Vol.510, pp.77--82, 2003.

Gc Protein-derived Macrophage Activating Factor (GcMAF): Isoelectric Forcusing Pattern and Tumoricidal Activity, Anticancer Research, Vol.23, No.6, pp.4451--4458, 2003.

Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity, Anticancer Research, Vol.25, No.6A, pp.3689--3695, 2005.

Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells (1993) http://www.jimmunol.org/cgi/content/abstract/151/5/2794

Protein chemical characterization of Gc globulin (vitamin D-binding protein) isoforms; Gc-1f, Gc-1s and Gc-2 Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics Volume 1774, Issue 4, April 2007, Pages 481-492 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B73DJ-4N1T1TG-2&_user=10&_coverDate=04%2F30%2F2007&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1483307365&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=17705d947ac64ac118f7fe0b759eea48&searchtype=a

General Info on Viruses: http://www.nlv.ch/Virologytutorials/Replication.htm http://en.wikipedia.org/wiki/Retrovirus

Deglycosylation status appears to not correlate with many cancer patients http://www.proteinscience.org/details/journalArticle/354539/Glycosylation_status_of_vitamin_D_binding_protein_in_cancer_patients.html

Original (Very First) Notice: http://www.catie.ca/catienews.nsf/c1213b02193fa85a85256f10006e9f7e/59637160717da4f785257520005c5bac!OpenDocument http://www.eatg.org/eatg/Global-HIV-News/Basic-Science/Cell-stimulant-touted-as-yet-another-cure-proceed-with-caution

PubMed Search of all papers including the word "GcMAF" in the title: http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=link&LinkName=pubmed_pubmed&from_uid=19031451 http://www.medkb.com/Uwe/Forum.aspx/nutrition/10094/Overcoming-the-Nagalase-Have-we-got-the-universal-HIV-and-cancer

Here's a study of GcMAF, a.k.a. Dbp-MAF, a.k.a. Gc Globulin sponsored by Creighton University (though not a treatment study for HIV infections):

http://clinicaltrials.gov/ct2/show/NCT00650780?term=Gc+Globulin&rank=1

Though, this study raises questions: http://www.proteinscience.org/details/journalArticle/354539/Glycosylation_status_of_vitamin_D_binding_protein_in_cancer_patients.html

http://liamscheff.com/daily/2010/05/19/an-onoff-switch-for-retroviruses-can-it-be-that-simple/

http://www.associatedcontent.com/article/1472171/cure_for_aids.html

http://pubs.acs.org/doi/abs/10.1021/pr8002936

http://ar.iiarjournals.org/content/24/5C/3361.abstract

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Neutrophil priming by cytokines and vitamin D binding protein (Gc-globulin): impact on C5a-mediated chemotaxis, degranulation and respiratory burst.

http://www.ncbi.nlm.nih.gov/pubmed/10698343

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Early article by Dr. Nobuto Yamamoto: http://www.jimmunol.org/cgi/content/abstract/157/4/1744

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Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF (2008) http://www.ncbi.nlm.nih.gov/pubmed/18058096

All the people working with GcMAF: http://www.biomedexperts.com/Concept.bme/22799/Vitamin_D-Binding_Protein

Many Links to papers on the Vitamin-D and the immune systems: http://www.vitamindcouncil.org/science/research/vitamin-d-in-innate-and-adaptive-immunity.shtml

Many Links to papers on the Vitamin-D and HIV and AIDS: http://www.vitamindcouncil.org/science/research/vitamin-d-and-hiv-and-aids.shtml

Type "GcMAF" into this search engine to find patents: http://www.wipo.int/tools/en/gsearch.html

More patent notices: http://www.faqs.org/patents/app/20090041793 http://www.rexresearch.com/yamamoto/yamamoto.htm

Here's an abstract on a study of the Glycosylation status of GcMAF in Cancer patients: http://www.ncbi.nlm.nih.gov/pubmed/19642159

Many Vitamin-D/GcMAF links here: http://www.vitamindcouncil.org/science/research/vitamin-d-and-breast-cancer.shtml

Agenda of 2007 Immunology Meeting mentions GcMAF curing HIV infection: http://www.monduzzi.com/proceedings/moreinfo/20070821.htm

2005 American Association for Cancer Research (AACR) Meeting Abstract: http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/1423-c

Treatment options for osteoporosis and osteopenia in HIV Disease: http://www.ncbi.nlm.nih.gov/pubmed/18413693

Vitamin D status in adolescents and young adults with HIV infection: http://www.ncbi.nlm.nih.gov/pubmed/16685057

Vitamin-D in prostate cancer: http://www.ncbi.nlm.nih.gov/pubmed/16886665

A potential role for vitamin D on HIV infection(2006)? http://www.ncbi.nlm.nih.gov/pubmed/16770943

Biological and Clinical aspects of GcMAF polymorphisms: http://www.ncbi.nlm.nih.gov/pubmed/16697362

Comment regarding nevirapine on Vitamin-D deficiency: http://www.ncbi.nlm.nih.gov/pubmed/19618997

Vitamin-D in prostate cancer: http://www.ncbi.nlm.nih.gov/pubmed/16886665

High frequency of Vitamin-D deficiency in ambulatory HIV patients: http://www.ncbi.nlm.nih.gov/pubmed/19108690

Vitamin-D levels and Immune Reconstitution Inflammatory Syndrome: http://www.ncbi.nlm.nih.gov/pubmed/19383117

Treatment options for osteoporosis and osteopenia in HIV Disease: http://www.ncbi.nlm.nih.gov/pubmed/18413693

Response from Dr. Young

Hi and thanks for posting.

I've not seen any recent presentation about Dr. Yamamoto's work on GcMAF. Indeed, I contacted him about this, but he did not offer any comment.

BY



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