GEMSP exerts a myelin-protecting role in the rat optic nerve Arturo Mangas 1 , Elena Vecino 2 , F. David Rodrı ´guez 3 , Michel Geffard 4,5 , Rafael Coven ˜as 1 1 Institute of Neurosciences of Castilla y Leo ´n (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), Salamanca, Spain, 2 University of the Basque Country, Department of Cell Biology and Histology, Group of Experimental Ophthalmo-Biology (GOBE), Faculty of Medicine, Leioa, Spain, 3 University of Salamanca, Department of Biochemistry and Molecular Biology, Research Group BMD, Salamanca, Spain, 4 IDRPHT, Talence, France, 5 Gemacbio, St Jean d’Illac, France Objectives: Chronic experimental autoimmune encephalomyelitis (EAE) was induced in rats to evaluate the potential protective effect of GEMSP, a mixture made up of fatty acids (FA), vitamins, and amino acids or their derivatives, linked to Poly-L-Lysine, on the myelin sheath of the optic nerve. Methods: To evaluate the effects of GEMSP on the optic nerve, animals were divided into three experimental groups: (1) EAE rats treated with GEMSP; (2) EAE rats treated with 0.9% NaCl; and (3) control, non-EAE rats. Using electron microscopy, we investigated the possibility that this new drug candidate has a myelin-protective role. Results: A marginally significant reduction in the thickness of the myelin around optic nerve medium-size axons (diameter between 0.8–1.3 mm) was found in EAE rats. Treatment of EAE rats with GEMSP ameliorated myelin damage. Significantly increased myelin thickness was found when animals in groups 2 and 3 were compared. However, the number of myelinated axons studied was not altered in groups 1 or 2 when compared to controls. Discussion: Our results suggest that in a model of demyelination, GEMSP protects and enhances the formation of the myelin sheath of the optic nerve and therefore could be a potential drug candidate to reduce optic nerve pathogenesis in multiple sclerosis (MS). Keywords: Demyelination, Experimental autoimmune encephalomyelitis (EAE), Multiple sclerosis (MS), Optic nerve Introduction Multiple sclerosis (MS) is a progressive chronic inflammatory autoimmune and neurodegenerative dis- ease affecting the central nervous system (CNS). Its etiology remains unknown. Focal leukocyte infiltration, which produces inflammation, followed by demyelina- tion, axonal degeneration, and loss, results in nerve cell dysfunction. 1,2 As the disease progresses, patients develop multiple disabilities. Multiple sclerosis appears more frequently in young adults (20–45 years of age) and affects twice as many women as men. 3 The highest incidence of onset occurs in the third decade of life. Commonly, MS causes ophthalmologic damage, includ- ing optic neuritis, diplopia, bilateral uveitis, oscillopsia, retinal periphlebitis, etc., all of which can severely impair vision. 4,5 Experimental autoimmune encephalomyelitis (EAE) is an animal model used for the study of MS since many similar clinical and histopathological features can be observed. Experimental autoimmune encephalomyelitis can be induced by the administration of peptides derived from myelin components, such as myelin basic protein, proteolipid protein, or myelin oligodendrocyte glycoprotein (MOG). 6 Experimental autoimmune ence- phalomyelitis is widely used for the evaluation of different drugs (beta interferon (IFN-beta), glatiramer acetate (GA), laquinimod, linomide, and GEMSP). 7–13 There are two classical models of EAE: (a) acute EAE, characterized by a clear EAE onset accompanied by inflammation of the CNS for a relatively short duration followed by nearly complete recovery of the animals and (b) chronic EAE, in which the animals present clinical signs for at least 2 months with several EAE relapses. In general, these animals exhibit irreversible damage of the CNS. 10,13 The main advantages of this latter model are that it appears to mimic the pathogen- esis of MS since the disease changes over long periods of time and no recovery of the clinical signs are evident. GEMSP is a recently designed combination of fatty acids (FA), antioxidants, free radical scavengers, and amino acids linked to poly-L-Lysine 14 . This new drug Correspondence to: David Rodriguez, Department of Biochemistry and Molecular Biology, University of Salamanca, Edificio Departamental, Campus Unamuno, 37007 Salamanca, Spain. Email: lario@usal.es ß W. S. Maney & Son Ltd 2013 DOI 10.1179/1743132813Y.0000000233 Neurological Research 2013 VOL. 35 NO.9 903