Fumarates for the treatment of multiple sclerosis: potential mechanisms of action and clinical studies

Abstract

All licensed disease-modifying drugs for the treatment of relapsing–remitting multiple sclerosis (MS) only display partial efficacy and hitherto require parenteral administration. Thus, there is a high demand for innovative and at the same time orally available MS therapeutics. Fumaric acids and their esters (FAE) may represent such a new class of compounds. FAE display immunomodulatory properties and may also exert neuroprotective effects, as shown in vitro as well as in experimental models of MS. A first Phase II study with the new, modified FAE BG00012/FAG-201 (BG-12) in relapsing–remitting MS revealed significant effects on MRI parameters such as gadolinium-enhancing lesions, T1 hypointense lesions and T2 lesion load after 24 weeks of treatment. The trial also underlined the safety and good tolerability of FAE that are already in clinical use for the systemic treatment of severe psoriasis. Presently, two Phase III studies are ongoing to investigate the clinical long-term efficacy of BG-12. In summary, FAE are potential candidates that may open a new therapeutic option for relapsing–remitting MS in the near future.

Keywords::

• autoimmune
• immunomodulation
• neuroprotection
• Nrf2 pathway
• T cell

Financial & competing interests disclosure

R Gold and M Stangel received research support and honoraria for activites with Bayer Health Care, BiogenIdec, Merck Serono and TEVA Pharma. R Linker received honoraria for activites with Bayer Health Care, Biogen Idec and TEVA Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.