Title:Mouse Models of Multiple Sclerosis: Lost in Translation?
Volume: 21
Issue: 18
Author(s): David Baker and Sandra Amor
Affiliation:
Keywords:
Animal models, experimental autoimmune encephalomyelitis, toxin models, multiple sclerosis, therapeutics, translation.
Abstract: Multiple sclerosis (MS) is a chronic neurological disorder of the central nervous system (CNS) leading
to progressive accumulation of neurological deficits arising from recurrent episodes of inflammation, demyelination
and neuronal degeneration. While the aetiology of the disease is unknown MS is widely considered to be the
result of aberrant T cell and antibody responses to CNS antigens giving rise to the common concept that MS is an
autoimmune disease or that there is an autoimmune component in the pathogenesis. This idea has lead to the development
of experimental autoimmune encephalomyelitis (EAE) mouse models of MS in which immunisation with
CNS antigens induces neurological and pathological signs of disease in mice. In addition to EAE models, injection
with neurotropic viruses has been used to examine how infections are implicated in the disease process and how
they may generate autoimmune responses in the CNS. Viral models are also crucial to investigate the impact of
blocking trafficking of immune responses into the CNS since an emerging side-effect of current immunotherapeutic approaches in MS is
the reactivation of viruses within the CNS. To investigate myelin damage and repair in the absence of the adaptive immune response,
toxin-induced demyelination using cuprizone, ethidium bromide and lysolecithin, which rapidly leads to remyelination when the toxins
are withdrawn, is also reviewed. Mice also lend themselves to the vast array of transgenic technologies to probe specific pathways as well
as the use of humanised transgenic mice to examine the impact of human molecules. Despite the vast array of mouse models EAE is the
most frequently exploited paradigm used to develop therapeutic approaches. However, despite over one thousand compounds used in the
treatment of EAE few have become licenced for treatment of MS so far. Thus, this review also debates the reasons for these failures in
mouse models as well as discusses how mouse models can be better utilised to provide more powerful preclinical tools to develop rational
therapies for multiple sclerosis.
