Myasthenia gravis (MG) is an
autoimmune disease caused by
complement-fixing
antibodies against
acetylcholine receptors (AChR);
antigen-specific CD4+ T cells, regulatory T cells (Tregs) and T helper (Th) 17+ cells are essential in antibody production. Target-specific therapeutic interventions should therefore be directed against
antibodies, B cells,
complement and molecules associated with T cell signaling. Even though the progress in the immunopathogenesis of the disease probably exceeds any other autoimmune disorder, MG is still treated with traditional drugs or procedures that exert a non-
antigen specific immunosuppression or
immunomodulation. Novel biological agents currently on the market, directed against the following molecular pathways, are relevant and specific therapeutic targets that can be tested in MG: (a) T cell intracellular signaling molecules, such as anti-CD52, anti-
interleukin (
IL) 2 receptors, anti- costimulatory molecules, and anti-Janus
tyrosine kinases (JAK1, JAK3) that block the intracellular cascade associated with T-cell activation; (b) B cells and their trophic factors, directed against key B-cell molecules; (c)
complement C3 or C5, intercepting the destructive effect of
complement-fixing
antibodies; (d)
cytokines and
cytokine receptors, such as those targeting
IL-6 which promotes antibody production and
IL-17, or the p40 subunit of
IL-12/1L-23 that affect regulatory T cells; and (e) T and B cell transmigration molecules associated with lymphocyte egress from the lymphoid organs. All drugs against these molecular pathways require testing in controlled trials, although some have already been tried in small case series. Construction of recombinant AChR
antibodies that block binding of the pathogenic
antibodies, thereby eliminating
complement and antibody-depended-cell-mediated cytotoxicity, are additional novel molecular tools that require exploration in experimental MG.