Immunomodulatory peptidomimetics for multiple sclerosis therapy—the story of glatiramer acetate (Copaxone)

Multiple sclerosis (MS) is a complex disease mediated by an autoimmune response to myelin components, inducing inflammation, demyelination and degeneration in the central nervous system. This chapter describes several approaches used to develop peptidomimetics based on components participating in the pathological processes of MS in an attempt to suppress the disease. This includes antigen-specific peptidomimetics and peptidomimetics that block activation signals. Glatiramer acetate (GA, or Copaxone) was originally designed as a peptidomimetic based on the myelin basic protein autoantigen in an attempt to induce experimental MS and was found to be one of the first MS-modifying therapies. GA is also the first, and so far the only, therapeutic agent to contain a copolymer as its active ingredient. The overall “pool” of various GA amino acid sequences engenders multiple peptidomimetic species that facilitate several modes of action, inducing immunomodulation as well as neuroprotection. Herein the unique GA mechanism of action is discussed.