{"id":6,"date":"2014-02-24T22:27:01","date_gmt":"2014-02-24T22:27:01","guid":{"rendered":"http:\/\/nagalase-test.de\/en\/?page_id=6"},"modified":"2026-03-10T09:58:28","modified_gmt":"2026-03-10T09:58:28","slug":"questions-and-answers","status":"publish","type":"page","link":"https:\/\/nagalase-test.de\/en\/questions-and-answers\/","title":{"rendered":"Questions and Answers"},"content":{"rendered":"

Click on the questions and get directly to the answer or read the questions and answers systematically from top to bottom.<\/p>\n

Questions:<\/h2>\n

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  1. What is \u201eNagalase\u201c?<\/a><\/li>\n
  2. Which role does Nagalase play?<\/a><\/li>\n
  3. More precisely: \u201eWhat is \u201eGc-MAF\u201c\u201c?<\/a><\/li>\n
  4. How is Nagalase thought to inactivate Gc-MAF?<\/a><\/li>\n
  5. “Nagalase Test”: What does this mean?<\/a><\/li>\n
  6. I would like a Nagalase test to be performed? How does it work?<\/a><\/li>\n
  7. What is the cost of the test and how will the test be billed?<\/a><\/li>\n
  8. Artificially produced Gc MAF for treating diseases<\/a><\/li>\n
  9. What other parameters can be relevant for a Gc-MAF therapy?<\/a><\/li>\n
  10. Summary<\/a><\/li>\n
  11. Scientific references<\/a><\/li>\n
  12. Explanation of key terms<\/a><\/li>\n<\/ol>\n

    <\/a><\/p>\n

    What is “Nagalase”?<\/h2>\n

    The so-called “Nagalase” is an endogenous enzyme that plays a role in sugar metabolism. The scientifically correct name is “N-acetyl- Galactosaminidase”. Nagalase can split off certain sugar molecules , namely N -acetyl- galactosamine , from large molecules.<\/p>\n

    Specifically, Nagalase may split off the N- acetyl galactosamine sugar side chain from the so-called “vitamin D -binding protein” (“DBP”).<\/p>\n

    DBP is found in serum and is also referred to as “Gc-Protein”.<\/p>\n

    Yamamoto and colleagues reported that tumors can produce Nagalase ( Yamamoto et al. 2008a , 2008b , 2008c , Reddi et al. , 2000). Moreover they reported that in tumor patients Nagalase serum levels mabe increased.<\/p>\n

    There is evidence that the \u00a0Nagalase produced by tumors \u00a0has an “immuno- suppressive” effect. It is thought that the Nagalse-mediated immune-suppression in cancer patients contributes to the growth of the existing tumor and the formation of metastases.<\/p>\n

    The immunosuppressive effect of Nagalase attributed to a mechanism in which Nagalase-mediated removal of sugar moieties \u00a0prevents the formation of the immune- stimulating factor Gc -MAF from Gc protein (more information about this mechanism, see below).<\/p>\n

    It is important to note that in the recent months two publications by Yamamoto and colleagues have been retractred b ythe Editors-In-Chief of the respectiv ejournals. The reasons given for this were \u201cirregularities in the documentation for institutional review board approval<\/strong>\u201c.<\/p>\n

    However, latest publications by Ward et al. (Am J Immunol, 2014) and Ruggiero et al. (Anticancer Research, 2014) support a possible role of GcMAFin cancer.<\/p>\n

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    <\/a><\/p>\n

    What is the role of Nagalase?<\/h2>\n

    Under normal (“physiologic”) conditions Nagalase is involved in the metabolism of sugar side chains in larger molecules.<\/p>\n

    The Nagalase produced by tumors is thought to have an immunosuppressive effect ( Saharuddin et al. 2002 , Yamamoto et al. , 1997).<\/p>\n

    Under diagnostic aspects, Nagalase determination in cancer patients is used to check whether immune-stimulatory therapy is appropriate (\u201ctherapy indication\u201d) or to track the response to therapeutic measures (“therapy monitoring”). Particularly Nagalase determination is used when patients are teated with \u00a0Gc- MAF.<\/p>\n

    There is a genetic disease in which the Nagalase synthesis is disturbed: “Schindler\u2019s Disease”. This disease is associated with disorders of the nervous system.<\/p>\n

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    <\/a><\/p>\n

    More precisely: What is “Gc-MAF”?<\/h2>\n

    The Gc-Protein has a sugar side chain consisting of three sugar molecules , namely N – acetyl galactosamine , galactose, and sialic acid \u00a0a so-called “tri- saccharide” (= “triple sugar”).<\/p>\n

    When sialic acid and galactose are removed from this \u00a0tri- saccharide, N -acetyl- galactosamine remains as a single sugar moiety.<\/p>\n

    For Gc-Protein modified in this manner a strong activating effect on macrophages has been described: this modified Gc-Protein is a “Macrophage-Activating Factor”, abbreviated as “MAF”.<\/p>\n

    More specifically the partially de-glycosylated Gc protein -derived macrophage-activating molecule is called “Gc -MAF” ( Saharuddin et al. 2002 Kuchiike et al. , 2013 Kisker et al. 2003)<\/p>\n

    It is assumed that this partial sugar elimination (de-glycosylation) from the Gc protein is accomplished under natural conditions by enzymes in immune cells, namely by a so-called “galactosidase” of B-Lymphocytes and a “sialidase” by T-Llymphocytes<\/p>\n

    Gc -MAF formed by immune cells in inflammatory and defense responses , is thought to have an important role in immune defense, but especially in the immune response against tumors ( Kisker et al. 2003 Thyer et al , 2013B , Uto et al. 2012 Kuchiike et al. , 2013).<\/p>\n

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    \r\nI would like to have a Nagalase-Test be performed
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    <\/a><\/p>\n

    How is Nagalase thought to inactivate Gc-MAF?<\/h2>\n

    The enzyme “Nagalase” completely eliminates the sugar side chain of the Gc protein: the thus-modified Gc protein can no longer be converted to Gc MAF, its immune-stimulatory effect is no longer available.<\/p>\n

    In other words, the effect of Nagalase on Gc Protein prevents the formation Gc -MAF. Insofar, tumor-derived \u00a0Nagalase may have immune-suppressive properties.<\/p>\n

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    \r\nI would like to have a Nagalase-Test be performed
    \r\n    How does it work ? What should I do?<\/a>\r\n<\/div>\r\n<\/div>\r\n<\/div>\n
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    <\/a><\/p>\n

    “Nagalase Test”: What does this mean?<\/h2>\n

    There are test procedures, by which the activity of Nagalase can be determined. The Nagalase is isolated from a serum sample and enzyme activity is measured in a quantitative manner.<\/p>\n

    This test procedure is known as “Nagalase-Test”.<\/p>\n

    Increased serum Nagalase levels have been described in many diseases, but especially in cancer ( Thyer et al. 2013B , Yamamoto et al. , 1997).<\/p>\n

    A decline of Nagalase values is interpreted as an as an indication of therapeutic response , especially when monitoring Gc-MAF therapy ( Korbelik et al. 1998 Thyer et al. 2013B , Yamamoto et al. 2008a , 2008b , 2008c ).<\/p>\n

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    \r\nI would like to have a Nagalase-Test be performed
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    <\/a><\/p>\n

    I would like a Nagalase test to be performed? How does it work?<\/h2>\n

    Your doctor may perform the test in collaboration with the medical laboratory of Prof. Kramer in Heidelberg.<\/p>\n

    For the test, a blood sample (serum) is taken and send in to the laboratory.<\/p>\n

    Deatailed information on sample generation<\/strong> can be found here<\/a>.<\/p>\n

    A request\/order form<\/strong> for the test can be found here<\/a>.<\/p>\n

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    \r\nI would like to have a Nagalase-Test be performed
    \r\n    How does it work ? What should I do?<\/a>\r\n<\/div>\r\n<\/div>\r\n<\/div>\n

    <\/a><\/p>\n

    What is the cost of the test and how will the test be billed?<\/h2>\n

    For privately-insured patients the billing is according to official fees for doctors (GO\u00c4).<\/p>\n

    Unfortunately, this test is currently not covered by statutory health insurance and needs to be \u00a0be paid by the patient. The price of self-pay is \u20ac 67.04.<\/p>\n

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    \r\nI would like to have a Nagalase-Test be performed
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    <\/a><\/p>\n

    Artificially produced Gc-MAF for treating diseases<\/h2>\n

    When the macrophage activating activity \u00a0of Gc-MAF became known, research was conducted towards synthetic production of Gc MAF and its use as an immune-stimulating agent.<\/p>\n

    The therapy with artificial GcMAF is thought to benefit from the fact that artificial GcMAF cannot be inactivated by Nagalase.<\/p>\n

    Accordingly, methods have been developed for in vitro<\/em> production of Gc-MAF which is then administered to patients ( Inui et al. , 2013, Thyer et al. 2013A , Uto 2012 , Yamamoto et al. 2008a , 2008b , 2008c ).<\/p>\n

    The measurement of serum Nagalase activity is used to explore whether artificial Nagalse might be an treatment option (therapy indication) and to assess the effect of Gc-MAf therapy (\u201ctherapy – monitoring”).<\/p>\n

    There are several providers of GcMAF.<\/p>\n

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    <\/a><\/p>\n

    What other parameters may be relevant for Gc -MAF therapy?<\/h2>\n

    Vitamin D levels and serum calcium<\/p>\n

    The optimum effect of the Gc- MAF appears to depend on optimal vitamin D levels. Recommended values are between 30 and 80 ng \/ ml.<\/p>\n

    Therefore, it is recommended to determine the vitamin D value in the serum prior to Gc -MAF therapy and, if necessary, to supplement vitamin D.<\/p>\n

    In parallel, it is recommended to determine the serum-calcium values and adjust the dose of vitamin D when elevated serum calcium levels are observed.<\/p>\n

    Genetics of the Vitamin D Receptor ( VDR)<\/p>\n

    Some authors described (Fabris et al 2012; Pacini et al 2012) that the effect of Gc -MAF depends on the genetic variants of the vitamin D receptor, the so-called “VDR genotypes “. In particular, the VDR variants “Fok 1” and “BSM1” were explored.<\/p>\n

    The best responding patients (\u201cresponders\u201d) seem to have the genotype FF \/ bb, followed by Ff \/ Bb . The genotype Ff \/ BB seems to be “low” responders.<\/p>\n

    Therefore, the information on VDR genotype was taken to set the dose for Gc-MAF treatment.<\/p>\n

    uPA receptor (uPA -R ) in serum<\/p>\n

    There are publications that suggest a role of the so-called “uPA receptor” (uPA – R) in the invasive growth of tumors and the formation of metastases. The serum levels of soluble uPA -R have been described as a prognostic factor for tumors ( Soydin\u00e7 et al. 2012 , Taubert et al. 2010).<\/p>\n

    In particular a connection between the effect of Gc MAF effect and uPA -R has been described : GC- MAF reduced the amount of uPA -R released by tumor cells ( Gregory et al 2010.).<\/p>\n

    Some scientists therefore recommend the determination of uPA \u2013R levels in serum as part of a Gc -MAF therapy monitoring in cancer patients.<\/p>\n

    Genetics of the Gc protein<\/p>\n

    Genetic variants have also been described for the Gc protein. To what extent these play a role in optimizing Gc- MAF therapy is still the subject of scientific debate.<\/p>\n

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    \r\nI would like to have a Nagalase-Test be performed
    \r\n    How does it work ? What should I do?<\/a>\r\n<\/div>\r\n<\/div>\r\n<\/div>\n
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    <\/a><\/p>\n

    Summary<\/h2>\n