Clinical Trials Report: Central & Peripheral Nervous Systems: Drugs in development for the treatment of multiple sclerosis: antigen-specific therapies

Abstract

In recent years, several new terms and concepts have been added to the lexicon of immune regulation, including: peripheral tolerance, anergy, activation-induced apoptosis, altered peptide ligand, and bystander suppression. At the same time, great strides were made in the identification of autoantigenic peptides and T-cell receptors (TCRs) involved in the pathology of multiple sclerosis (MS). The convergence of these discoveries and limitations of current MS treatments sparked the inception of several novel therapeutic approaches that were applied to animal models and T-cell clones. This review summarises the research that has led to the development of various proposed antigen-specific therapies for MS. Included are approaches that target specific components of the TCR:peptide: MHC II triad involved in the activation of autoreactive T-cells. Also included are approaches which purport to induce specific cells to inactivate cells in their vicinity, a form of ‘specific non-specificity’ generally termed bystander suppression. The trial status of these antigen-specific therapies and results to date are summarised.

Key Words:

• altered peptide ligand
• anergy
• antigen-specific therapy
• apoptosis
• bystander suppression
• multiple sclerosis