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 idea l result, the conversion of a destructive or pathogenic autoimmune res ponse into one of benign autoimmunity would also be highly desirable. In either case the use of the antigenic epitope, which is the target o f the destructive immune response, would ideally be employed so as to give specificity to the protection without the need for long-term immu nosuppression. This review describes a number of different approaches using various forms, doses, and routes of injection of specific neuroa ntigen to inhibit the different clinical varieties of autoimmune encep halomyelitis in a number of animal models; all done with the view to t ranslating the findings into the clinic for the treatment of multiple sclerosis. We conclude that any treatment strategy for multiple sclero sis (MS) must have a number of features: it must be clinically accepta ble, specific, longlasting, require only short-term treatment, able to shut off ongoing disease, and have the potential to prevent or deal w ith epitope spreading. Few of the approaches we describe fulfill all o f these criteria. We suggest that investigations of new adjunctive age nts to be used with a specific antigen be pursued, and that currently the use of chimeric proteins or DNA vaccination with or without the ne w adjunctives may hold the most hope for the future.