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.
