title: Novel future therapeutic options in myasthenia gravis.
abstract: BACKGROUND
  Myasthenia Gravis (MG) is an autoimmune disease caused by complement-fixing antibodies against the acetylcholine receptors (AChR). Antigen-specific CD4+ T cells, Tregs and Th17+ are also necessary. Consequently, antibodies, B cells, molecules associated with signalling pathways on T helper cells, cytokines and complement are targets for more specific treatment options.
  
  
  OBJECTIVE
  Because available immunosuppressive therapies cause unacceptable side effects after long-term use or are not always effective in inducing remission, novel biological agents directed against the following targets might be options for future therapies in MG: 1) T cell Intracellular Signaling Pathways associated with T cell activation, such as monoclonal antibodies against CD52, Interleukin 2-receptor (IL-2 R), co-stimulatory molecules or compounds inhibiting Janus tyrosine kinases JAK1, JAK3; 2) B cells, against key B cell-surface molecules or trophic factors B cell activation factor (BAFF) and a proliferating inducing ligand (APRIL); 3) Complement, against C3 or C5 that intercept membranolytic attack complex formation; 4) Cytokines and cytokine receptors, including IL-6, IL-17, the p40 subunit of IL12/1L-23, and GM-CSF; and 5) Lymphocyte migration molecules. Construction of recombinant AChR antibodies that block the binding of the pathogenic antibodies, can be a future molecular tool.
  
  
  CONCLUSIONS
  New biological agents are in the offing for future therapies in MG. Their efficacy needs to be secured with vigorously controlled clinical trials and weighted against excessive cost and rare complications.
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA. mdalakas@med.uoa.gr
authors.forename: Marinos C
authors.initials: MC
authors.lastname: Dalakas
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology / Q000627:therapeutic use; D001685:Biological Factors / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D007167:Immunotherapy / Q000191:economics; D008213:Lymphocyte Activation; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011950:Receptors, Cholinergic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001685:Biological Factors; D011950:Receptors, Cholinergic