Fumaric Acid Esters as Potential Therapies for Treating Degenerative Retinal Disease

Fumaric Acid Esters (FAE) are found naturally in some plants (Fumaria officinalis) and mushrooms. In Germany, a mixture of fumaric acid esters (Fumaderm®) is licensed for the treatment of psoriasis [1]. A clinical formulation of dimethyl fumarate (referred to as gastro-resistant Dimethyl Fumarate (DMF) or delayed-release DMF) is approved in the United States, New Zealand, Australia, European Union, Switzerland and Canada for the treatment of Multiple Sclerosis (MS) [2-5]. Immediately after oral intake, DMF is acted upon by intestinal esterases to form Monomethyl Fumarate (MMF); hence, MMF is the primary bioactive ingredient [6]. Following DMF ingestion, circulating MMF concentrations peak between 2-2.5 hrs and the half-life of the metabolite is around 12 hrs [7]. Recent studies have reported the use and potential efficacy of MMF in the treatment of various diseases other than those named above. Though quite heterogenous with respect to etiology, the common denominator amongst them all appears to be inflammation and oxidative stress. Inflammation and oxidative stress figure prominently in various degenerative diseases of the retina (i.e., diabetic retinopathy, sickle cell retinopathy, age-related macular degeneration and glaucoma). Given the impact of these factors on the development and progression of degenerative retinal diseases, others and we have evaluated the potential benefit of MMF in various in vitro and in vivo experimental conditions relevant to the pathogenesis of retinal disease.