GcMAF
{{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.{{cite book|title=Galactosidases — Advances in Research and Application |url=https://books.google.com/books?id=YrFfapkTmp8C&pg=PA52|date=21 June 2013|publisher=Scholarly Editions|isbn=978-1-4816-8801-7|page=52}} It has been falsely promoted as a treatment for various medical conditions, but claims of its benefits are not supported by evidence.
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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.
|source =Public warning issued by the Anticancer Fund}}
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). The resulting protein may be a macrophage activating factor (MAF).{{cite journal | first1 = Suneil | last1 = Malik | first2 = Lei | last2 = Fu | first3 = David James | last3 = Juras | first4 = Mohamed | last4 = Karmali | first5 = Betty Y. L. | last5 = Wong | first6 = Agnes | last6 = Gozdzik | first7 = David E. C. | last7 = Cole |title=Common variants of the vitamin D binding protein gene and adverse health outcomes |journal=Critical Reviews in Clinical Laboratory Sciences |volume=50 |issue=1 |pages=1–22 |date=January–February 2013 |pmid=23427793 |pmc=3613945 |doi=10.3109/10408363.2012.750262 }} 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.{{cite journal | first = David M. | last = Mosser | title = The many faces of macrophage activation | journal = Journal of Leukocyte Biology | volume = 73 | issue = 2 | pages = 209–212 |date=February 2003 | pmid = 12554797 | doi = 10.1189/jlb.0602325| doi-access = free }}
False claims
Since around 2008, GcMAF has been promoted as a cure for cancer, HIV, autism{{cite news| last=Miller | first=Michael E. | url=https://www.washingtonpost.com/news/morning-mix/wp/2015/07/16/the-mysterious-death-of-a-doctor-who-peddled-autism-cures-to-thousands/ |title=The mysterious death of a doctor who peddled autism 'cures' to thousands| newspaper= Washington Post |date=16 July 2015 |access-date=26 August 2015}} and other conditions.{{cite web|title=Press Release: Regulator warns against GcMAF made in unlicensed facility in Cambridgeshire - GOV.UK|url=https://www.gov.uk/government/news/regulator-warns-against-gcmaf-made-in-unlicensed-facility-in-cambridgeshire|publisher=Medicines and Healthcare products Regulatory Agency|language=en|date=3 February 2015}}
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. {{cite journal | doi = 10.1002/jmv.21376| title = Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF)| journal = Journal of Medical Virology| volume = 81 | issue = 1| pages = 16–26| date = January 2009| last1 = Yamamoto | first1 = Nobuto| last2 = Ushijima | first2 = Naofumi| last3 = Koga | first3 = Yoshihiko | pmid=19031451| doi-access = free}}{{Retracted|doi=10.1002/jmv.24060|pmid=25328930|http://retractionwatch.com/2014/08/21/second-study-of-widely-touted-cancer-and-hiv-cure-retracted/ Retraction Watch|intentional=yes}}{{cite journal | title = Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF) | first1 = Nobuto | last1 = Yamamoto | first2 = Hirofumi | last2 = Suyama | first3 = Nobuyuki | last3 = Yamamoto | first4 = Naofumi | last4 = Ushijima | doi = 10.1002/ijc.23107 | pmid = 17935130 | journal = International Journal of Cancer | volume = 122 | issue = 2 | pages = 461–467 | date = 15 January 2008| s2cid = 15258428 }}{{Retracted|doi=10.1002/ijc.29014|pmid=25180398|http://retractionwatch.com/2014/07/25/paper-about-widely-touted-but-unapproved-cure-for-cancer-autism-retracted/ Retraction Watch|intentional=yes}}{{cite journal | doi = 10.1007/s00262-014-1616-x| pmid = 25297451| title = Retraction Note to: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF| journal = Cancer Immunology, Immunotherapy| volume = 63| issue = 12| pages = 1349| year = 2014| last1 = Yamamoto | first1 = N. | last2 = Suyama | first2 = H. | last3 = Nakazato | first3 = H. | last4 = Yamamoto | first4 = N. | last5 = Koga | first5 = Y. | doi-access = free | pmc = 11028656 }}{{cite journal | doi = 10.1002/ijc.29014| title = Retraction| journal = International Journal of Cancer| volume = 135| issue = 6| pages = 1509| date = 15 September 2014| s2cid = 221774191}} Retraction reasons also included methodological errors in the studies.{{cite web |author=Ivan Oransky |title =Paper about widely touted but unapproved "cure" for cancer, autism retracted |url=http://retractionwatch.com/2014/07/25/paper-about-widely-touted-but-unapproved-cure-for-cancer-autism-retracted/2014 |publisher=Retractionwatch |date=25 July 2014}}{{cite web|title=Tracking retractions as a window into the scientific process Yet another study of widely touted cancer "cure" retracted|url=http://retractionwatch.com/2014/10/10/yet-another-study-of-widely-touted-cancer-cure-retracted/|website=Retraction Watch|access-date=28 July 2015|date=2014-10-10}} The integrity of the research, conducted by Nobuto Yamamoto and colleagues, that originally prompted claims regarding cancer and HIV has been questioned.{{cite web | url = https://www.anticancerfund.org/en/gcmaf-story-exploitation-and-lies | title = GcMAF: a story of exploitation and lies| date = 2017-12-08| publisher = Anticancer Fund | access-date=2018-07-28}}
The UK Medicines and Healthcare products Regulatory Agency 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.{{cite web | last=Arney | first=Kat | url=http://scienceblog.cancerresearchuk.org/2008/12/03/cancer-cured-for-good-gc-maf-and-the-miracle-cure/ | title='Cancer cured for good?' – Gc-MAF and the miracle cure (revised 25 July 2014) | publisher=Cancer Research UK | date=3 December 2008 | access-date=10 February 2015 | archive-date=17 October 2014 | archive-url=https://web.archive.org/web/20141017155937/http://scienceblog.cancerresearchuk.org/2008/12/03/cancer-cured-for-good-gc-maf-and-the-miracle-cure/ | url-status=dead }}
In 2014 the Belgian Anticancer Fund communicated serious concerns about published studies on GcMAF by Yamamoto and colleagues.
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.{{cite news |url=http://www.fdanews.com/articles/170150-uks-mhra-shuts-down-gcmaf-plant |title=UK's MHRA shuts down GcMAF plant |publisher=FDA News |date=1 March 2015}}
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,{{cite news |url=https://guernseypress.com/news/2018/09/27/man-behind-gcmaf-is-facing-jail/ |title=Man behind GcMAF is facing jail |last=Mann |first=Nick |publisher=Guernsey Press|date=27 September 2018}} and sentenced to 15 months of jail.{{cite news |url=https://www.bbc.com/news/world-europe-guernsey-46359949 |title=Cancer 'cure' boss David Noakes jailed for 15 months |publisher=BBC |date=27 November 2018}}
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.{{cite news |url=https://www.notretemps.com/high-tech/actualites/cinq-britanniques-condamnes-pour-la-afp-202104,i241976 |title=Cinq Britanniques condamnés pour la vente d'un médicament "miracle" sur internet |publisher=Notretemps |language=fr |date=15 April 2021 |access-date=17 April 2021 |archive-date=17 April 2021 |archive-url=https://web.archive.org/web/20210417083942/https://www.notretemps.com/high-tech/actualites/cinq-britanniques-condamnes-pour-la-afp-202104,i241976 |url-status=dead }}
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.{{cite web|url=https://www.businessinsider.com/in-closed-facebook-groups-pushing-unproven-treatments-2019-8|title=Unlicensed medical 'cures' are flourishing in closed Facebook groups, where cancer treatments — and even surgery — are sold beyond the reach of the law|last=Porter|first=Tom|website=Business Insider|date=2019-10-18|access-date=2019-11-14}} Jewell is not a medical doctor.{{cite news|url=https://www.bbc.com/news/health-37654666|title=Investigation over cancer 'cure' GcMAF|last=Evans|first=Ruth|date=2016-10-16|access-date=2019-11-14|language=en-GB}}
First Generation GcMAF
Gc protein-derived macrophage-activating factor (GcMAF).
GcMAF initially conceptualized by Nobuto Yamamoto in 1991,{{cite journal |last1=Toshio Inui, Kaori Makita, Hirona Miura, Akiko Matsuda, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Takahito Nishikata, Hitoshi Hori And Norihiro Sakamoto |title=Case Report: A Breast Cancer Patient Treated With Gcmaf, Sonodynamic Therapy And Hormone Therapy |journal=Anticancer Research |date=2014 |page=34, 4589-4594}} has been researched as a possible cancer treatment.{{cite journal |last1=Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Hitoshi Hori And Norihiro Sakamoto |title=Clinical Experience Of Integrative Cancer Immunotherapy With Gcmaf |journal=Anticancer Research |date=2013 |page=33, 2917-2920}} 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.{{cite journal |last1=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 |title=Degalactosylated/Desialylated Human Serum Containing Gcmaf Induces Macrophage Phagocytic Activity And In Vivo Antitumor Activity |journal=Anticancer Research |date=2013 |volume=33 |issue=7 |pages=2881–2885 |pmid=23780974 |url=https://ar.iiarjournals.org/content/33/7/2881}}{{cite journal |last1=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 |date=2023 |title=Effect Of Degalactosylated Bovine Glycoprotein Formulations Maf And M Сapsules On Lymphopenia And Clinical Outcomes In Hospitalized Covid-19 Patients: A Randomized Clinical Trial |url=https://www.researchsquare.com/article/rs-2879067/v1 |journal=Research Square|doi=10.21203/rs.3.rs-2879067/v1 }}
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),{{cite web |title=United States Patent Uto Et Al. Us008747919b2 Us 8,747,919 B2 Jun. 10, 2014 Pharmaceutical Composition And Method Of Preparing Same |url=https://patents.google.com/patent/US8747919B2/en?oq=US8747919B2 |access-date=}}{{cite web |title=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 |url=https://patents.google.com/patent/US9409972B2/en?oq=US9409972B2}}{{cite web |title=United States Patent Uto Et Al. Usoo9670268b2 Us 9,670,268 B2 *Jun. 6, 2017 Pharmaceutical Composition And Method Of Preparing Same |url=https://patents.google.com/patent/US9670268B2/en?oq=US9670268B2}} Japan (2015),{{cite web |title=Japan Platform For Patent Information Wo-A1-2013/038997 |url=https://www.j-platpat.inpit.go.jp/c1800/PU/JP-5860817/19D41912E942877F9B8CA6E0110F250DFE2BB4C3DF34EBD537B9FBA0E7EA60F5/15/ja}} the EU (2016),{{cite web |title=European Patent Specification Pharmaceutical Composition And Manufacturing Method Therefor Wo 2013/038997 (21.03.2013 Gazette 2013/12) |url=https://patents.google.com/patent/EP2687218B1/en?oq=EP2687218B1}} Australia (2016),{{cite web |title=Australian Government Ip Australia 2012309586 Pharmaceutical Composition And Manufacturing Method Therefor 2012-09-07 Granted |url=https://pericles.ipaustralia.gov.au/ols/auspat/applicationDetails.do?applicationNo=2012309586}} Israel (2018).
See also
References
{{Reflist|30em}}
{{Unproven and disproven cancer treatments}}