The relevance of animal models in multiple sclerosis research
Introduction
Multiple Sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system [1]. It is the leading cause of non-traumatic disability among young adults and has great socioeconomic impact in developed countries. According to the National MS Society, approximately 400,000 people have been diagnosed with MS in the United States, with 200 new cases added every week. MS is a very heterogeneous disease from a variety of standpoints, including its clinical presentation, radiological features, immuno-pathological subtypes, response to therapy and genetic associations. A recent detailed analysis of a large series of active demyelinating lesions revealed four distinct patterns of immune-pathology [2]. The first two patterns feature well-demarcated perivascular demyelination and relative sparing of oligodendrocytes. Lesions in patterns I and II show close similarities to T cell-mediated and T cell- and antibody-mediated autoimmune demyelination. Lesions in patterns III and IV are suggestive of oligodendrogliopathy in an inflammatory background [3] (Fig. 1).
To date, there is still no definitive cause and no effective cure for MS, although several genetic and environmental risk factors have been identified, and a number of partially effective preventive treatment modalities are now available to modify the disease course. Therefore, animal models of MS are needed to further explore mechanisms of disease initiation and progression and test various therapeutical and restorative approaches. Given that MS is a complex disease with an unclear etiology; a single animal model is unlikely to accurately represent all aspects of pathology and clinical features of human MS. However, the availability of three major animal models of MS enables studies of several relevant features of the human disease.
Section snippets
Animal models of MS
Over the past several decades, a number of animal models have been developed in order to understand a variety of aspects of human MS. The main driving force for animal studies stems from the following limitations of human studies: overall limited access to human MS tissue, biopsies are rarely performed and autopsy samples are usually biased towards a chronic, burnt-out stage; experimental circumstances cannot easily be modified in clinical trials and mechanistic studies addressing disease
Conclusions
There is no single animal model that can capture the entire spectrum of heterogeneity of human MS and its variety in clinical and radiological presentation. However, over the last several decades, useful and relevant animal models have been developed that represent selected aspects of the human disease. Depending on the specific research question, the rational selection of appropriate animal models is likely to yield outcomes that will result in translatable findings applicable to MS. Despite
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