TREATMENT OF EXPERIMENTAL MYASTHENIA-GRAVIS WITH CYCLOSPORIN-A

Cyclosporin A (CsA) [an immunosuppressive agent] treatment of rats with experimental autoimmune myasthenia gravis (EAMG), an antibody-mediated autoimmune disorder of acetycholine receptors (AChR) at neuromuscular junctions, was studied. CsA treatment at the time of primary immunization suppressed the antibody responses to AChR virtually completely. Following 2 wk of CsA, the AChR-immunized rats responded like naive controls to a further challenge of AChR. Treatment of ongoing EAMG results in a reduction of AChR antibody by > 50%. The secondary response to a challenge of AChR was presented by CsA treatment, but a very large challenge dose in adjuvant partially overwhelmed the effect of CsA. CsA treatment also prevented the loss of AChR at neuromuscular junctions, as compared with untreated EAMG controls (P < 0.02). The efficacy of CsA in suppressing ongoing and secondary hetero- and autoimmune responses against AChR in EAMG encourages its ultimate application in autoimmune disease of man, such as MG. Its usefulness will depend on the ability to determine effecive dose of CsA that is well tolerated.