Modeling a complex disease: multiple sclerosis

The recent decades have shown that multiple sclerosis (MS) is not a uniform disease entity with common etiology, but rather a disease or syndrome characterized by a heterogeneous pattern of manifestations and pathological principles. Apart from the older distinctions of the Devic's disease from the standard Western form of relapsing remitting MS or the more Asian form of opticospinal MS, specific pathological patterns indicating distinct etiologies have been established by analyses of biopsies and autopsies. Further, the distinct responses of patients to drugs targeting either specific cell types or immunoregulatory mechanisms such as Rituximab or IFNβ clearly demonstrate the heterogeneity of the disease and their driving mechanisms. Finally, the late neurodegenerative phase, which severe cases of MS patients experience, is now in the focus of research. Here, a mechanism independent of or with low participation of the adaptive immune system takes place, which is therefore not treatable by current immunotargeting drugs. In this review, we will summarize previous and latest efforts to establish new mouse models mirroring these distinct disease patterns and pathways.