Therapeutic potential of novel compounds targeting mitochondrial pathways in mouse models of MS

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelination of the neurons present in the central nervous system (CNS). The exact etiology of MS development is unclear, but various environmental and genetic factors might play a role in initiating the disease. Current treatments for MS only enhance the quality of life and reduce the symptoms. One of these treatments is dimethyl fumarate (DMF), commercially known as Tecfidera, which can be taken orally. Experimental autoimmune encephalomyelitis (EAE) is a mouse model that is used to study the pathophysiology of MS disease as well as the effects of possible therapeutic agents. In this study we investigated the effects of several novel compounds designed at Sharjah institute for Medical Research (SIMR). Two of these compounds; SIMR1281 and SIMR1707, showed robust therapeutic effects against EAE disease when used preventively, prophylactically, or therapeutically as they reduced the clinical scores of EAE mice. The histological and immunohistochemistry evaluations showed reduced clinical features such as signs of inflammation, demyelination, and infiltration of T cells into the brains of the EAE mice, as compared to vehicle treated, or untreated EAE mice. Future experiments using proteomics and metabolomics could reveal the possible mechanisms of action of these compounds. Aim: • To investigate the effects of the novel compounds SIMR1281 and SIMR1707 on EAE mice. Objectives: 1- The first objective of this study is to investigate if there could be any potential therapeutic effects therapy of these compounds on EAE mice. 2- The second objective is to examine the mechanisms of action (MOA) of the compounds which show ameliorating effects against EAE.