Saturday, March 30, 2013

FDA announces approval of dimethyl fumarate


Dimethyl Fumarate
On March 27, 2013 Dimethyl fumarate has won FDA approval to treat relapsing-remitting forms of multiple sclerosis and will be sold under the name Tecfidera also known as BG-12, manufactured by Biogen Idec.
The drug has been used for many years in Europe to treat psoriasis, and since the 1980’s as a fungicide.
Dimethyl fumarate is unlike all previous MS “disease-modifying drugs” (DMDs) which all work by eliminating T lymphocytes and/or preventing them from crossing the blood-brain barrier.  It thus represents a “radical change in multiple sclerosis pathogenesis” according to van Horssen a long-time leading MS researcher.  Instead, dimethyl fumarate is an “anti-oxidant” which means that it reduces “reactive oxygen species” which in turn reduces free radicals. For years health specialists have been extolling the importance of anti-oxidants such as green tea and turmeric to delay ageing.  But recent research has demonstrated that the oligodendrocytes that make myelin are extremely sensitive to free radicals. Dr. van Horssen reported at ECTRIMS in 2011 that dimethyl fumarate exerts its protective effect via activation of the nuclear-factor-E2 (Nrf2) transcriptional pathway that is involved in the production of antioxidant enzymes necessary for oxidative stress defense.  He stated that distinct Nrf2 activators like dimethyl fumarate boost antioxidant enzyme production in oligodendrocytes and limit ROS-mediated oligodendrocyte death.
Two placebo-controlled phase III trials served as the basis for the FDA approval.  A total of about 2,700 patients were studied. In addition to comparing the drug with placebo, dimethyl fumarate was also compared to glatiramer acetate (Copaxone).
At the 2013 annual meeting of the American Academy of Neurology Robert Fox, MD reported that MRI T2 lesions were reduced by 72% at 6 months and 82% at two years.  Gadolinium-enhancing lesions were reduced by 83% at 6 months and 83% at two years.  This is much better than the immunosuppressants drugs.  It was also superior to Copaxone.
The main side effect was gastrointestinal complaints.  There has also been a case report of one 72 year-old man who developed PML on Fumaderm the name of the drug in Germany that has recently been purchased by Biogen.
Biogen obtained a use patent for dimethyl fumarate in 2009.  It is important to note this was a “use” patent; Biogen did not invent dimethyl fumarate that has been available for decades.  They patented the preparation of it in enteric-coated micro-tablets to reduce the GI irritation in a dose designed to deliver approximately 100 mg of fumaric acid to treat multiple sclerosis and other conditions.

Dr. van Horssen also compared Biogen’s formulation called BG-12 to Protandim, an over-the-counter Nfr2 activator dietary supplement in an in vitro (human oligodendrocyte cells in a petri dish, not in vivo, skeptical and gullible human beings).   He found that Protandim was actually superior to BG-12, as the “most potent induction of Nfr2-driven antioxidant enzyme production in oligodendrocytes” (ECTRIMs 2011).

Biogen recommends taking the 120mg capsule twice daily, increasing to two (2) twice daily after a few weeks.  Based on their 2009 patent this would be approximately 100mg of fumeric acid, but we are still looking into this conversion question.  Although Biogen has not announced how much they will charge for their new drug, it is likely that it will be about the same as the other DMDs, i.e. about $40,000 per year.  Protandim is expensive but costs about $40 per month or $480 per year, but currently will not be reimbursed by insurance companies.  It contains several herbs that are high in fumeric acid including green tea extract and turmeric extract.  The company that makes Protandim typically recommends one tablet a day.  David Perlmutter MD (author of “BrainRecovery.com”) recommends that patients with neurodegenerative disorders such as MS take one twice daily of  another brand of Nfr2 Activator made by Xymogen which also contains green tea and turmeric extracts.  One can take the herbs themselves but it will be important to make sure that an adequate quantity is taken and there may be more GI irritation at higher doses. Terry Wahls MD (author of “Minding My Mitochondria”) recommends 3 cups per day of intensely colors vegetables and fruits such as beets, carrots, squash, berries and peaches. Non-denatured whey is also a source of anti-oxidant stimulation.  Ann Boroch CNC (author of “Healing Multiple Sclerosis”) also recommends anti-oxidants ideally from foods but also several supplements including  Antioxidant Supreme made by Gaia Herbs.  We are continuing to look into the appropriate conversion between Tecfidera and other formulations.  Since Biogen has spent many millions to prove dimethyl fumarate’s efficacy, it will be worthwhile to try to obtain adequate quantities of similar Nrf2 activators from other formulations.

Summary:  A multi-million dollar FDA trial has proven that taking Nfr2 activators dramatically reduces MS.  The mechanism of action is the reduction of oxidative stress, not immunosuppression.  This mechanism is in keeping with the inflammation/brain vein drainage model (in contrast to the orthodox autoimmune attack on intact myelin by T cells model).  We believe that everyone should be taking it, whether prescribed by neurologists – Tecfidera, or by naturopaths – Protandim, Xymogen, diet, or herbal supplements. 


4 comments:

  1. Great article Arlene! Out of curiosity, would you mind sharing which way Devin gets his Nfr2 activator...whether its through Protandim,Xymogen, etc.
    Thanks Team Hubbard.....we all <3 you!

    ReplyDelete
    Replies
    1. Devin has been on Protandim for the past 2 1/2 years, in addition to lots of other supplements. We decided on the Protandim, based on the research and we thought 1 extra pill per day rather than a few more extra supplements would help with his compliance. Dr Perlmutter's Xymogen Nrf2 activator seems quite good and the recommended dosage for someone with neurodegenerative disease is 2 per day(as per Dr Perlmutter). We are trying to get in touch with someone at Protandim to find out their recommendations for someone with a neurodegenerative disease....it might be more than the 1 per day dose. I hope this helps.

      Delete
  2. Thanks for sharing Arlene!
    After reading this article I have also started Protandim. If you do find out about their recommendations for those with a neurodegenerative disease please share that info...if it means taking 2 pills a day for a better result then Im all for it :)

    Thanks again for all your work! All the best to you and your family - especially Devin <3

    ReplyDelete
  3. https://www.facebook.com/notes/francesco-paolo-ruggieri/fumaria-ottimo-depuratore-del-sangue-e-lunga-vita/616467821700031 ; CHIMNEY, excellent blood purifier AND LONG LIFE.
    http://www.etnobotanica.org/2007/12/20/la-fumaria-officinalis-papaveracee/;
    POPULAR NAMES AND INTERNATIONAL Fumosterno, Fumoterra, Gall of the Earth, Adetina Grass, Grass Calderugia, Common Fumitory, Drug Fumitory, Wax-Dolls Beggary, Erdrauch, Fumeterre, Capa De Reina, Moleirinha Erva, Erva Pombinha, Duivekervel, Jordrök, Guessis, Shahtredj PERIOD BALSAMICO March BOTANICAL DESCRIPTION herbaceous annual plant SMALL WITH PINK FLOWERS AND COLLECTED IN DARK RED As an apex RACEMI
     
    FITOTERAPIA
    DRUGS USED flowering tops ACTIVE Alkaloids isochinolici (protoberberine), fumarina, flavonoids, fumaric acid, mucilage, mineral salts, vitamins. HERBS SYNERGIC BURDOCK BOLDO ARTICHOKE MILK THISTLE Erisimo ESCHOLTZIA COMMON ASH ASH SPINOSO GENZIANA MAIS MELISSA PEPPERMINT Ononide Piscidia HORSERADISH SARSAPARILLA TARASSACO LINDEN OFFICINALE RED VINE VERY LOW TOXICITY CONTRAINDICATIONS in high doses may OBTAIN DIARRHEA. AVOID THE ASSOCIATION WITH DRUGS AND PLANTS sedating. DRUG INTERACTIONS OR INCOMPATIBILITY SEDATIVES QUALITY BUSINESS fitoterapica SPECIFICATIONS AND EMPLOYEE FROM THE FORMS OF ACTION THERAPEUTIC INTERESTED fitoterapica ARTERIES MOUTH oropharyngeal Gallbladder and bile TEETH LIVER LIVER AND BILE SALIVARY GLANDS INTESTINE nasal mucosa DIGESTIVE ORGANS ORGANS OF FABRICS EO various body excretory organs BONES - CARTILAGES - JOINTS KIDNEY CIRCULATION ENDOCRINE SYSTEM IMMUNE SYSTEM CENTRAL NERVOUS SYSTEM SKIN FABRIC STOMACH TUBE gastro-intestinal WHOLE BODY PERIPHERAL BLOOD VESSELS URINARY TRACT PROPERTIES: + + + + + + ANFOCOLERETICO carminative - antifermentative + + + choleretic + + + DIGESTIVE eupeptic BITTER PURE hepatoprotector antihepatotoxic + + + + + + THE LIVER spasmolytic liver and bile ducts cholagogue + + + + + + DRAINAGE DETOX PURIFYING dermoprotettivo DIURETIC + + + + + antispasmodic antispasmodic diaphoretic sudorific OR + + EXCITING bulbar centers EXCITING SPINAL CORD INSTRUCTIONS GENERAL TONIC + + + + + + + CHOLECYSTITIS gallbladder and biliary colic DYSPEPSIA + + + + + + or maldigestion INFLAMATIONS (BILE) + + + METEORISM flatulence, and intestinal fermentation + + ACNE (DETOX) + + ALLERGIES AND ATHEROSCLEROSIS ARTERIOSCLEROSIS + + + + gallstones Gallbladder and bile DERMATOSIS + + + + + + atonic dyspepsia Hepatobiliary and INTOXICATION FAILURE OF THE LIVER AND POISONING + + + + ALCOHOL POISONING ALSO POOR salivation (SCIALAGOGO) halitosis + + + ARTHRITIS ASTHENIA OR LOW DEPRESSION AND NERVOUS OR MENTAL STRESS + + + DIATHESIS arthritic ECZEMA GASTRITIS atonic + + + FLU HYPERTENSION (hypotensive PERIPHERAL) TEAS OF TOBACCO + ERBEOFFICINALI ALLERGY AND COOLING. HAY ATHEROSCLEROSIS DIGESTIVE AROMATIC EXTRACTS: Fumitory Herbal Infusion 2-5% 2-3 cups a day before meals Fumitory Fluid extract 1 g = XXXV gtt Used in atonic chronic gastritis with reduced salivation. 2-5 g per day Fumitory dry extract titrated in Title alkaloids 0.1 g dose 2-3 times per day Fumitory Tincture Used in atonic chronic gastritis with reduced salivation. XXX gtt 3 times a day NOTES FITOTERAPIA The pharmacological activities are those experimentally confirmed choleretic - hepatoprotective and anti-spastic digestive tract. The protopina together to monometilfumarato antiepatotossica have shown activity similar to that of silymarin. The plant is therefore indicated for digestive disorders caused by congestive hepatobiliary postprandial heaviness - flatulence - bad breath and constipation.
    NOTES SCIENTIFIC UTILITY AND MISCELLANEOUS
    GOOD TO KNOW PLANTS purifying and DRENANTI .....

    ReplyDelete