Fumaric acid inhibits NF-kappaB, may treat multiple sclerosis

A psoriasis drug that may have use as a treatment for multiple sclerosis

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-kappaB by increasing the levels of reduced glutathione.

A total of 13 studies have confirmed that 50-70% of psoriasis patients have show an approximate 75% reduction in their “psoriasis area and servitiy index” (PASI) after 4 months of treatment with fumaric acid. However, side effects can be significant, and include nausea, vomiting and diarrhea in up to 30% of patients. Those 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 such as psoriasis (or multiple sclerosis.)

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 efficacy of fumaric acid in the treatment of multiple sclerosis may result from its ability to inhibit NF-kappaB. If so, it suggests that other inhibitors of NF-kappaB might also be useful in MS.

The publication:

March, 2009

Fumaric Acid and its esters: an emerging treatment for multiple sclerosis.

Summary of the abstract

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 are licensed for the treatment of psoriasis. Several lines of evidence have demonstrated immune regulatory effects.

Clinical studies in psoriasis showed a reduction of peripheral T-lymphocytes due to the ability of fumaric acid to induce natural cell death.

In vitro studies with the ester dimethyl fumarate describe NF-kappaB inhibition.

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