Biology:GcMAF

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Short description: Protein produced by artificial modification of vitamin D-binding protein

GcMAF (or Gc protein-derived macrophage activating factor) is a protein produced by modification of vitamin D-binding protein.[1] It has been falsely promoted as a treatment for various medical conditions, but claims of its benefits are not supported by evidence.

Once proclaimed a 'magic protein' capable of curing cancer, GcMAF has been proven ineffective. The case sheds light on how far scammers are willing to go to exploit desperate cancer patients and their families for financial gain.

Public warning issued by the Anticancer Fund[2]

Biochemically, GcMAF results from sequential deglycosylation of the vitamin D-binding protein (the Gc protein), which is naturally promoted by lymphocytes (B and T cells).[3] The resulting protein may be a macrophage activating factor (MAF).[3] MAFs are lymphokines that control the expression of antigens on the surface of macrophages, and one of their functions is to make macrophages become cytotoxic to tumors.[4]

False claims

Since around 2008, GcMAF has been promoted as a cure for cancer,[5] HIV,[6] autism[7] and other conditions.[8]

Three out of four of the original studies authored by Yamamoto (published between 2007 and 2009) were retracted by the scientific journals in which they were published in 2014, officially due to irregularities in the way ethical approval was granted.[6][9][10][11] Retraction reasons also included methodological errors in the studies.[12][13] The integrity of the research, conducted by Nobuto Yamamoto and colleagues, that originally prompted claims regarding cancer and HIV has been questioned.[5][2]

The UK Medicines and Healthcare products Regulatory Agency[8] and Cancer Research UK has warned the public about spurious claims of clinical benefits, misleadingly based on reduced levels of the alpha-N-acetylgalactosaminidase enzyme (also known as nagalase), whose production might be increased in many cancers.[5]

In 2014 the Belgian Anticancer Fund communicated serious concerns about published studies on GcMAF by Yamamoto and colleagues.[2]

In 2015 the UK Medicines and Healthcare products Regulatory Agency (MHRA) closed a factory in Milton, Cambridgeshire owned by David Noakes' company Immuno Biotech that manufactured GcMAF for cancer treatment.[14]

In September 2018 Noakes pleaded guilty in UK to manufacturing a medicinal product without a manufacturer's licence, selling or supplying medicinal products without market authorisation, and money laundering,[15] and sentenced to 15 months of jail.[16] In April 2021 Noakes pleaded guilty in France to manufacturing and selling fake medicinal products and cosmetics by Internet and sentenced to 4 years of jail.[17]

A 2019 Business Insider report detailed the activities of Amanda Mary Jewell, who sold GcMAF for years as a(n unlicensed) cure for several medical conditions, including cancer and autism.[18] Jewell is not a medical doctor.[19]

First Generation GcMAF

Gc protein-derived macrophage-activating factor (GcMAF).

GcMAF initially conceptualized by Nobuto Yamamoto in 1991,[20] has been researched as a possible cancer treatment.[21] Previous research efforts involved the isolation of Gc protein (1f1f subtype) from human serum through an affinity column modified with 25-hydroxyvitamin D3. GcMAF was enzymatically derived from the isolated Gc protein.[22][23]

New Generation of GcMAF from Japan

The 2nd and 3rd generation GcMAF were developed by the Japanese organizations which hold the patents: in the USA (2014, 2016, 2017),[24][25][26] Japan (2015),[27] the EU (2016),[28] Australia (2016),[29] Israel (2018).

See also

  • List of ineffective cancer treatments

References

  1. ↑ Galactosidases — Advances in Research and Application. Scholarly Editions. 21 June 2013. p. 52. ISBN 978-1-4816-8801-7. https://books.google.com/books?id=YrFfapkTmp8C&pg=PA52. 
  2. ↑ 2.0 2.1 2.2 "GcMAF: a story of exploitation and lies". Anticancer Fund. 2017-12-08. https://www.anticancerfund.org/en/gcmaf-story-exploitation-and-lies. 
  3. ↑ 3.0 3.1 Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y. L.; Gozdzik, Agnes; Cole, David E. C. (January–February 2013). "Common variants of the vitamin D binding protein gene and adverse health outcomes". Critical Reviews in Clinical Laboratory Sciences 50 (1): 1–22. doi:10.3109/10408363.2012.750262. PMID 23427793. 
  4. ↑ Mosser, David M. (February 2003). "The many faces of macrophage activation". Journal of Leukocyte Biology 73 (2): 209–212. doi:10.1189/jlb.0602325. PMID 12554797. 
  5. ↑ 5.0 5.1 5.2 Arney, Kat (3 December 2008). "'Cancer cured for good?' – Gc-MAF and the miracle cure (revised 25 July 2014)". Cancer Research UK. http://scienceblog.cancerresearchuk.org/2008/12/03/cancer-cured-for-good-gc-maf-and-the-miracle-cure/. 
  6. ↑ 6.0 6.1 (Retracted) Yamamoto, Nobuto; Ushijima, Naofumi; Koga, Yoshihiko (January 2009). "Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF)". Journal of Medical Virology 81 (1): 16–26. doi:10.1002/jmv.21376. PMID 19031451. 
  7. ↑ Miller, Michael E. (16 July 2015). "The mysterious death of a doctor who peddled autism 'cures' to thousands". Washington Post. https://www.washingtonpost.com/news/morning-mix/wp/2015/07/16/the-mysterious-death-of-a-doctor-who-peddled-autism-cures-to-thousands/. 
  8. ↑ 8.0 8.1 "Press Release: Regulator warns against GcMAF made in unlicensed facility in Cambridgeshire - GOV.UK" (in en). Medicines and Healthcare products Regulatory Agency. 3 February 2015. https://www.gov.uk/government/news/regulator-warns-against-gcmaf-made-in-unlicensed-facility-in-cambridgeshire. 
  9. ↑ (Retracted) Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki; Ushijima, Naofumi (15 January 2008). "Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF)". International Journal of Cancer 122 (2): 461–467. doi:10.1002/ijc.23107. PMID 17935130. 
  10. ↑ Yamamoto, N.; Suyama, H.; Nakazato, H.; Yamamoto, N.; Koga, Y. (2014). "Retraction Note to: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF". Cancer Immunology, Immunotherapy 63 (12): 1349. doi:10.1007/s00262-014-1616-x. PMID 25297451. 
  11. ↑ "Retraction". International Journal of Cancer 135 (6): 1509. 15 September 2014. doi:10.1002/ijc.29014. 
  12. ↑ Ivan Oransky (25 July 2014). "Paper about widely touted but unapproved "cure" for cancer, autism retracted". Retractionwatch. http://retractionwatch.com/2014/07/25/paper-about-widely-touted-but-unapproved-cure-for-cancer-autism-retracted/2014. 
  13. ↑ "Tracking retractions as a window into the scientific process Yet another study of widely touted cancer "cure" retracted". 2014-10-10. http://retractionwatch.com/2014/10/10/yet-another-study-of-widely-touted-cancer-cure-retracted/. 
  14. ↑ "UK's MHRA shuts down GcMAF plant". FDA News. 1 March 2015. http://www.fdanews.com/articles/170150-uks-mhra-shuts-down-gcmaf-plant. 
  15. ↑ Mann, Nick (27 September 2018). "Man behind GcMAF is facing jail". Guernsey Press. https://guernseypress.com/news/2018/09/27/man-behind-gcmaf-is-facing-jail/. 
  16. ↑ "Cancer 'cure' boss David Noakes jailed for 15 months". BBC. 27 November 2018. https://www.bbc.com/news/world-europe-guernsey-46359949. 
  17. ↑ "Cinq Britanniques condamnés pour la vente d'un médicament "miracle" sur internet" (in fr). Notretemps. 15 April 2021. https://www.notretemps.com/high-tech/actualites/cinq-britanniques-condamnes-pour-la-afp-202104,i241976. 
  18. ↑ Porter, Tom (2019-10-18). "Unlicensed medical 'cures' are flourishing in closed Facebook groups, where cancer treatments — and even surgery — are sold beyond the reach of the law". https://www.businessinsider.com/in-closed-facebook-groups-pushing-unproven-treatments-2019-8. 
  19. ↑ Evans, Ruth (2016-10-16). "Investigation over cancer 'cure' GcMAF" (in en-GB). https://www.bbc.com/news/health-37654666. 
  20. ↑ Toshio Inui, Kaori Makita, Hirona Miura, Akiko Matsuda, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Takahito Nishikata, Hitoshi Hori And Norihiro Sakamoto (2014). "Case Report: A Breast Cancer Patient Treated With Gcmaf, Sonodynamic Therapy And Hormone Therapy". Anticancer Research: 34, 4589-4594. 
  21. ↑ Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Hitoshi Hori And Norihiro Sakamoto (2013). "Clinical Experience Of Integrative Cancer Immunotherapy With Gcmaf". Anticancer Research: 33, 2917-2920. 
  22. ↑ Daisuke Kuchiike, Yoshihiro Uto, Hirotaka Mukai, Noriko Ishiyama, Chiaki Abe, Daichi Tanaka, Tomohito Kawai, Kentaro Kubo, Martin Mette, Toshio Inui, Yoshio Endo And Hitoshi Hori (2013). "Degalactosylated/Desialylated Human Serum Containing Gcmaf Induces Macrophage Phagocytic Activity And In Vivo Antitumor Activity". Anticancer Research 33 (7): 2881–2885. PMID 23780974. https://ar.iiarjournals.org/content/33/7/2881. 
  23. ↑ Toshio Inui, Oksana Kruglova, Olga Martyneko, Kostiantym Martyneko, Vadym Tieroshyn, Anatoli Gavrylov, Kentaro Kubo Borys Kutsyn, Alla Kubashko, Zoryana Veklych, Yurika Terashima, Martin Mette And Galyna Kutsyna (2023). "Effect Of Degalactosylated Bovine Glycoprotein Formulations Maf And M Сapsules On Lymphopenia And Clinical Outcomes In Hospitalized Covid-19 Patients: A Randomized Clinical Trial". Research Square. doi:10.21203/rs.3.rs-2879067/v1. https://www.researchsquare.com/article/rs-2879067/v1. 
  24. ↑ "United States Patent Uto Et Al. Us008747919b2 Us 8,747,919 B2 Jun. 10, 2014 Pharmaceutical Composition And Method Of Preparing Same". https://patents.google.com/patent/US8747919B2/en?oq=US8747919B2. 
  25. ↑ "United States Patent (10) Patent No.: Us 9,409,972 B2 Uto Et Al. (45) Date Of Patent: Pharmaceutical Composition And Method Of Preparing Same *Aug. 9, 2016". https://patents.google.com/patent/US9409972B2/en?oq=US9409972B2. 
  26. ↑ "United States Patent Uto Et Al. Usoo9670268b2 Us 9,670,268 B2 *Jun. 6, 2017 Pharmaceutical Composition And Method Of Preparing Same". https://patents.google.com/patent/US9670268B2/en?oq=US9670268B2. 
  27. ↑ "Japan Platform For Patent Information Wo-A1-2013/038997". https://www.j-platpat.inpit.go.jp/c1800/PU/JP-5860817/19D41912E942877F9B8CA6E0110F250DFE2BB4C3DF34EBD537B9FBA0E7EA60F5/15/ja. 
  28. ↑ "European Patent Specification Pharmaceutical Composition And Manufacturing Method Therefor Wo 2013/038997 (21.03.2013 Gazette 2013/12)". https://patents.google.com/patent/EP2687218B1/en?oq=EP2687218B1. 
  29. ↑ "Australian Government Ip Australia 2012309586 Pharmaceutical Composition And Manufacturing Method Therefor 2012-09-07 Granted". https://pericles.ipaustralia.gov.au/ols/auspat/quickSearch.do. 



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