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Methotrexate?

Discussion in 'General Treatment' started by energyoverload, Jul 4, 2010.

  1. energyoverload

    energyoverload Senior Member

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    Hi Everyone,

    I remember hearing how a few people on this forum had quite a good improvement of symptoms whilst on methotrexate for various concurrent diseases. I am aware that there are quite a few potential side effects of this drug, but do you think this is an option worth considering with my doctor? I am just sick to death of getting next to no relief, as are many. Is anyone out there still taking this drug and reaping the benefits?

    I've read how methotrexate inhibits DNA and RNA synthesis via folate inhibition - do you think this could have implications for treating XMRV - for those who are positive of course. If you inhibit RNA synthesis you prevent XMRV infecting the cells??

    Thanks for any feedback/ ideas,

    Jake
     
  2. energyoverload

    energyoverload Senior Member

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  3. richvank

    richvank Senior Member

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    Hi, Jake.

    Methotrexate acts by blocking the enzymes thymidylate synthase, GAR transformylase, AICAR transformylase, and dihydrofolate reductase (DHFR). The first promotes formation of thymidine, which is needed to make DNA. The next two enzymes are needed to make purines, which are needed to make both DNA and RNA. The fourth is the enzyme that allows folic acid to be utilized by the body, as well as converting dihydrofolate to tetrahydrofolate, which can be used to make coenzymes for all the functions of folates in the body.

    When methotrexate is given as chemotherapy, such as for cancer, it is given together with leucovorin (folinic acid) to counter the depletion of folate metabolites that is produced by blocking DHFR, while still inhibiting DNA and RNA synthesis. If methotrexate were to be considered for use in CFS, I would say that adding folinic acid, as well as 5-methyl tetrahydrofolate (FolaPro or Metafolin) would be very important, because the folate metabolites are already depleted in CFS because of the partial block of methionine synthase, which links the methylation cycle with the folate cycle.

    As you may know, when methotrexate is given, it mainly affects cells that divide rapidly, because they have the biggest demands for new DNA and RNA. This includes cancer cells, but it also includes cells in the bone marrow that produce new blood cells, as well as the enterocytes (cells lining the intestine). Since people with CFS often already have problems with their digestive systems, and some have a tendency toward macrocytic anemia, I would not be very enthusiastic about giving methotrexate to PWCs. However, please note that I am neither a physician nor a pharmacologist.

    I don't know what has been reported in the past about the effects of PWCs taking methotrexate, but I would be surprised if there were benefits to doing this, unless they came from treating comorbid cancer, psoriasis or rheumatoid arthritis.

    Best regards,

    Rich
     
  4. energyoverload

    energyoverload Senior Member

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    Rich,

    Thanks for all really useful info. If I were to take it I would definetely add Folinic Acid to minimize side effects. In Rheumatoid Arthritis some doctors seem to think it modulates Adenosine in some way, and this could be a big part in how it modifies the disease. All interesting stuff!

    Thanks!

    Jake
     

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