Fumaric acid was originally therapeutically used in psoriasis. Several lines of evidence have demonstrated immunomodulatory but also neuroprotective 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 dimethylfumarate (DMF) described an inhibitory effect on nuclear factor kappa B (NF-κB)-dependent transcription of tumor necrosis factor-alpha (TNF-α) induced genes in human endothelial cells. Animal experiments in the mouse model of central nervous system demyelination, MOG-induced experimental autoimmune encephalomyelitis, revealed a clear preservation of myelin and axonal density in the plaque. Molecular studies showed that this is based on the antioxidative mechanism of action via induction of the transcription factor Nrf-2. A phase II clinical trial in relapsing-remitting multiple sclerosis (RRMS) patients with dimethylfumarate showed a significant reduction in the number of gadolinium enhancing lesions after 24weeks.
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