Fumaric acid is widely used in Germany (where it is known as Fumaderm®) in the treatment of psoriasis. It’s mechanism of action is uncertain, but it is believed to act primarily via the inhibition of NF-kB through by increasing the levels of reduced glutathione.
A total of 13 studies have confirmed that 50-70% of psoriasis patients show an approximate 75% reduction in their “psoriasis area and servitiy index” (PASI) after 4 months of treatment. However, side effects can be significant, and include nausea, vomiting and diarrhea in up to 30% of patients. These side effects limit the duration of treatment to 6 weeks, which of course limits the usefulness of this product in the treatment of chronic disease.
Fumarate is known to be an immunomodulator, which is one reason for its present consideration as a possible new drug for the treatment of multiple sclerosis.
In a recent phase II study involving 257 patients, fumarate reduced by 69% the average number of lesions on MRI between weeks 12 and 24, reduced newly enlarging lesions by about 50% and reduced the annualized relapse rate by 32%. Adverse events included headache, infections, GI symptoms and slightly increased liver enzymes, all of which were reversible.
The publication:
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Curr Neuropharmacol. 2009 Mar;7(1):60-4.
Fumaric Acid and its esters: an emerging treatment for multiple sclerosis.
Moharregh-Khiabani D, Linker RA, Gold R, Stangel M.
Department of Neurology, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany;
Summary of the abstract – or read the free full text publication
Fumaric acid is an intermediate product of the citric acid cycle that is a source of intracellular energy in the form of adenosine triphosphate (ATP).
At present, fumaric acid esters (FAE) are licensed for the treatment of psoriasis. Several lines of evidence have demonstrated immunomodulatory effects for FAE. Clinical studies in psoriasis showed a reduction of peripheral CD4(+)- and CD8(+)-T-lymphocytes due to the ability of FAE to induce apoptosis. In vitro studies with the ester dimethyl fumarate (DMF) described an inhibitory effect on nuclear factor kappa B (NF-kB)-dependent transcription of tumor necrosis factor-alpha (TNF-alpha) induced genes in human endothelial cells. Animal studies using a model of central nervous system demyelination, MOG-induced experimental autoimmune encephalomyelitis (EAE), revealed a reduction of microglia and macrophages in inflamed lesions. A phase II clinical study in relapsing-remitting multiple sclerosis (RRMS) patients with a modified fumaric acid ester, BG-12, showed as “proof of principle” a significant reduction in the number of gadolinium enhancing lesions after 24 weeks of treatment as compared to placebo. Further phase III studies have now started to explore the long-term efficacy of FAE.
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