Dimethyl fumarate: a Janus-faced substance?

Introduction: Dimethyl fumarate (DMF) has been used as fungicide, but oral DMF activates anti-inflammatory and anti-oxidative pathways that are beneficial in the treatment of psoriasis. BG-12, a specific formulation of DMF, has been approved very recently for the treatment of relapsing-remitting multiple sclerosis (RRMS), which is characterized by both autoimmune lymphocytes leading to inflammation and mitochondrial alterations associated with oxidative stress. Areas covered: This review describes the pharmacokinetics and the mode of action of DMF, with a focus on molecular and cellular pathways, and discusses clinical results of DMF in RRMS treatment. To identify relevant publications, the author searched the PubMed database by using appropriate keywords and by searching for references cited within the obtained articles. Expert opinion: DMF demonstrated efficacy in several RRMS outcome measures related to disease activity and severity, but results on disability progression have been inconsistent. The overall safety profile might qualify DMF for long-term use, the frequency of side effects such as gastrointestinal complaints and flushing might hamper treatment adherence of MS patients. Since DMF covalently binds to intracellular proteins, the fate of this molecule in the body might need thorough long-term observation during clinical use.