Reply to Handunnetthi and Ramagopalan: UV radiation, experimental autoimmune encephalomyelitis, and multiple sclerosis

Abstract

Handunnetthi and Ramagopalan have questioned the validity of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) (1), the model we have used in our studies relating to MS (2). As with any animal model of human disease, the EAE model has its limitations. For example, in the mice, the disease is induced through immunization, as opposed to occurring spontaneously, as is the case with MS. Despite these problems, the EAE model has been instrumental in MS research. The EAE model has provided insight into the underlying mechanisms of MS pathology. Preclinical work in the EAE model has directly led to the development of three different treatment modalities for MS, including glatiramer acetate, mitoxantrone, and natalizumab (3). The EAE model also allows researchers the manipulation of mice genetically that simply is not possible with human subjects. Therefore, although studies in the EAE model cannot be “unequivocally extrapolated” to answer questions relating to MS, they certainly provide a starting point for the exploration of whether UV radiation, vitamin D, or both are involved in determining MS susceptibility.