Experimental myasthenia gravis (MG) in animals, and in particular experimental autoimmune MG in rodents, serves as excellent models to study possible novel therapeutic modalities for MG. The current treatments for MG are based on
cholinesterase inhibitors, general
immunosuppressants, and
corticosteroids, broad
immunomodulatory therapies such as
plasma exchange or
intravenous immunoglobulins (IVIGs), and
thymectomy for selected patients. This stresses the need for
immunotherapies that would specifically or preferentially suppress the undesirable autoimmune response without widely affecting the entire immune system as most available treatments do. The available animal models for MG enable to perform preclinical studies in which novel therapeutic approaches can be tested. In this review, we describe the different therapeutic approaches that were so far tested in experimental models of MG and discuss their underlying mechanisms of action. These include
antigen -
acetylcholine receptor (AChR)-dependent treatments aimed at specifically abrogating the humoral and cellular anti-AChR responses as well as immunomodulatory approaches that could be used either alone or in conjunction with
antigen-specific treatments or alternatively serve as
steroid sparing agents. The
antigen-specific treatments are based on fragments or
peptides derived from the
acetylcholine receptor (AChR) that would theoretically deviate the anti-AChR autoimmune response away from the muscle target or on ways to target AChR-specific T- and B- cell responses or
antibodies. The immunomodulatory modalities include cell-based and non-cell-based ways to affect or manipulate key players in the autoimmune process such as regulatory T cells, dendritic cells,
cytokine networks, and
chemokine and costimulatory signaling as well as
complement pathways. We also describe approaches that attempt to affect the
cholinergic balance, which is impaired at the neuromuscular junction. In addition to enabling to test the feasibility of novel approaches, experimental MG enables to perform analyses of existing treatment modalities, which cannot be performed in human MG patients. These include studies on the mode of action of various
immunosuppressants and on IVIGs. Hopefully, the vast repertoire of therapeutic approaches that are studied in experimental models of MG will pave the way to clinical studies that will eventually improve the management of MG.