Dimethyl fumarate

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid.



Approved by the U.S. Food and Drug Administration as a  treatment option for adults with relapsing multiple sclerosis.



Tecfidera is trade name.



DMF is thought to have immunomodulatory properties without causing significant immunosuppression.



It is marketed for the treatment of psoriasis in some countries.



An oral formulation to treat adults with relapsing multiple sclerosis.



For multiple sclerosis, the doses are 120 mg and 240 mg , with a maximum daily dose of 480 mg.



A Cochrane systematic review found moderate quality evidence of a reduction in the number of people with relapsing remitting MS that had relapses over a two-year treatment period with DMF versus placebo, as well as low quality evidence of a reduction in worsening disability, and an overall need for higher quality studies with longer follow-up.



It is a lipophilic, highly mobile molecule in human tissue, and is rapidly attacked by the detoxifying agent glutathione.



It is then metabolized to monomethyl fumarate (MMF) prior to entering systemic circulation.



It is a prodrug.



DMF and MMF mechanisms of action are unclear.



DMF and MMF have been shown to reduce the expression of micro-RNA-21, which is essential for the production of pathogenic cells in multiple sclerosis.



They can  epigenetically regulate the expression of micro-RNA-21 via the metabolic-epigenetic interplay in developing immune cells.



DMF and MMF main activities are considered to be immunomodulatory.



DMF and MMF shift T helper cells (Th) from the Th1 and Th17 profile to a Th2 phenotype. 



Elimination is via exhalation of CO2, with small amounts excreted through urine or feces.



In the treatment of psoriasis, the most common adverse events are gastrointestinal events, flushing and lymphopenia.



Other adverse effects include:  progressive multifocal leukoencephalopathy (PML) and Fanconi syndrome, which are considered rare. 



Adverse effects for MS include:  flushing and gastrointestinal events, such as diarrhea, nausea and upper abdominal pain.



Risks include: anaphylaxis and angio-oedema, PML, lymphopenia and liver damage.



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