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Fumaric Acid and its esters: an emerging treatment for multiple sclerosis
D Moharregh-Khiabani1, R A Linker, R Gold
1Department of Neurology, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Current Neuropharmacology
|September 2, 2009
Summary
Fumaric acid esters (FAE) show promise for treating multiple sclerosis by reducing inflammatory lesions. These compounds, already used for psoriasis, demonstrate immunomodulatory effects and induce apoptosis in T-lymphocytes.
Area of Science:
- Biochemistry
- Immunology
- Neuroscience
Background:
- Fumaric acid is a key citric acid cycle intermediate.
- Fumaric acid esters (FAE) are currently used to treat psoriasis.
- FAE possess demonstrated immunomodulatory effects.
Purpose of the Study:
- To evaluate the efficacy of fumaric acid esters (FAE) in treating multiple sclerosis.
- To investigate the immunomodulatory mechanisms of FAE.
Main Methods:
- Clinical studies in psoriasis patients.
- In vitro studies with dimethyl fumarate (DMF).
- Animal studies using experimental autoimmune encephalomyelitis (EAE) model.
- Phase II clinical trial with BG-12 in relapsing-remitting multiple sclerosis (RRMS) patients.
Main Results:
- FAE treatment reduced CD4(+) and CD8(+) T-lymphocytes in psoriasis patients by inducing apoptosis.
- Dimethyl fumarate (DMF) inhibited NF-kappaB-dependent TNF-alpha gene transcription.
- FAE treatment reduced microglia and macrophages in EAE lesions.
- BG-12 significantly reduced gadolinium-enhancing lesions in RRMS patients compared to placebo in a Phase II trial.
Conclusions:
- Fumaric acid esters (FAE) exhibit significant therapeutic potential for multiple sclerosis.
- FAE demonstrate broad immunomodulatory effects relevant to autoimmune diseases.
- Further Phase III studies are warranted to confirm long-term efficacy of FAE in MS.
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