Animal models of multiple sclerosis for the development and validation of novel therapies – potential and limitations

Abstract

Various types of experimental autoimmune encephalomyelitis (EAE) reflect some of the pathogenetic, clinical, and therapeutic features of the different forms of multiple sclerosis (MS), thereby, providing some, albeit limited, insight into the molecular and cellular basis of the human disease. Specific questions of MS therapy including the search for new therapeutic targets and strategies and their validation require investigations in different available EAE models. A survey is given of experimental therapeutic approaches that are currently under study with the most promising examples of monoclonal antibodies, gene therapy, stem cell transplantation and orally applied small molecular weight disease-modifying drugs. Reasons for therapy failure and adverse side-effects of some experimental trials are discussed. Precaution is advised, if results of new experimental approaches are translated into clinical practice.

Animal models of intestinal fibrosis: new tools for the understanding of pathogenesis and therapy of human disease

“…In these models clues can be found to identify initiating, perpetuating, and reversing events of intestinal fibrosis, thereby allowing the creation of conceptual pathophysiological frameworks. On the other hand, differences between animal and human biological responses cannot be dismissed (86), and precaution must be taken when results of experimental systems are translated into clinical practice (87). Although animal models will never fully reproduce the complexity of human diseases, they can investigate and compare early events vs. late events, and this may lead to the development of new pathophysiology-based therapies.…”

Anti-inflammatory effect by lentiviral-mediated overexpression of IL-10 or IL-1 receptor antagonist in rat glial cells and macrophages

“…69 This study showed that rIL-1ra or rIL-10 when overexpressed within the CNS during the remission phase of disease by means of a LV vector, clearly reduced clinical symptoms during the relapse, supporting the role of locally produced pro-inflammatory cytokines, including IL-1, in the relapse phase of cr-EAE. Although we are aware of the limitations when extrapolating results obtained by viral vectormediated gene expression in animal models to the real human disease, as shown for other MS treatments 70,71 we consider the use of low immunogenic LV vectors expressing either IL-10 or IL-1ra of therapeutic interest to prevent relapses in human MS.…”

Restoring the balance between disease and repair in multiple sclerosis: insights from mouse models

“…The development of mouse models of the immunological aspects of MS has proven extremely valuable in identifying antigenic and cellular components important in demyelination (Furlan et al, 2009;Mix et al, 2008). The disease that develops in these models depends on the specific antigenic stimulation and the genetic background of the host animal (Baxter, 2007;Krishnamoorthy and Wekerle, 2009).…”