Importance of the Non-responder in Deciphering Animal Behavior of Experimental Autoimmune Encephalomyelitis

Abstract

To bring new drugs and therapies to the clinic, preclinical studies are mandated to establish the efficacy and possible mechanism of action. For the best results, animal models that closely mimic the target disease are required. Prior to initiating large-scale multi-centered clinical trials, the Food and Drug Administration in the United States often dictates that the efficacy and safety of new drugs need to be demonstrated in two animal models, and not just two different strains of mice. This set of rules has not always been followed when testing drugs for autoimmune diseases. Given that many of these diseases, including fibromyalgia, multiple sclerosis, arthritis, and even autism fall into spectrums of disorders, determining an appropriate animal model is complicated. With regard to multiple sclerosis, the primary animal model is experimental autoimmune encephalomyelitis (EAE) [1,2]. In mouse or rat models of EAE, there are several ways to induce the disorder including viral infection, genetic or adoptive transfer of activated T cells, or chemical/antibody producing systemic injections [1-5]. These models have been described by numerous investigators with each pointing out the strengths and weaknesses [2,6,7]. However, less attention is paid to the major form of MS which is a relapsingremitting form, and few animal models of EAE provide a reliable and consistent profile of this disease. Viral infection and adoptive transfer result in a progressive form of EAE – most likely mimicking chronic progressive MS. However, chronic progressive MS only affects 15% of the population, leaving a majority of the people with relapsingremitting MS at onset without a reasonable animal model.