Approaches to the treatment of central nervous system autoimmune disease using specific neuroantigen

The ultimate aim in the treatment of autoimmune disease is to restore self-tolerance to the autoantigen(s) in question. In lieu of this ideal result, the conversion of a destructive or pathogenic autoimmune response into one of benign autoimmunity would also be highly desirable. In either case the use of the antigenic epitope, which is the target of the destructive immune response, would ideally be employed so as to give specificity to the protection without the need for long-term immunosuppression. This review describes a number of different approaches using various forms, doses, and routes of injection of specific neuroantigen to inhibit the different clinical varieties of autoimmune encephalomyelitis in a number of animal models; all done with the view to translating the findings into the clinic for the treatment of multiple sclerosis. We conclude that any treatment strategy for multiple sclerosis (MS) must have a number of features: it must be clinically acceptable, specific, long-lasting, require only short-term treatment, able to shunt off ongoing disease, and have the potential to prevent or deal with epitope spreading. Few of the approaches we describe fulfill all of these criteria. We suggest that investigations of new adjunctive agents to be used with a specific antigen be pursued, and that currently the use of chimeric proteins or DNA vaccination with or without the new adjunctives may hold the most hope for the future.