Leflunomide prevents the development of experimentally induced myasthenia gravis.
Myasthenia gravis is an autoimmune disease in which autoantibodies specific to the acetylcholine receptor (AChR) are formed, leading to a gradual destruction of the receptors in muscles that are responsible for picking up nerve impulses, and results in weakness and eventual loss of muscle function. The novel immunomodulating drug leflunomide (HWA 486) has been shown to be very effective in preventing and halting ongoing disease in an array of experimental autoimmune disorders and reactions leading to organ graft rejection. Further, recent data from phase II clinical trials indicate that this drug is efficacious and is safe in humans with rheumatoid arthritis. In the studies reported here, we found that rats immunized with AChR-protein and not receiving leflunomide developed experimental myasthenia gravis (EMG) between day 7 and 11 post-immunization, and about 79% of these animals expressed clinical signs of disease. Treatment of AChR-protein immunized rats with leflunomide, from the day of disease induction, totally suppressed the development of EMG. Thus, the results we have obtained using leflunomide in EMG indicate that this drug could be beneficial in combating myasthenia gravis in humans.
Vidic-Dankovic
B
B
Immunology Research Center, Belgrade, Serbia Montenegro.
Kosec
D
D
Damjanovic
M
M
Apostolski
S
S
Isakovic
K
K
Bartlett
R R
RR
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D007114:Immunization; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077339:Leflunomide; D009157:Myasthenia Gravis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014101:Torpedo
D001323:Autoantibodies; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D011950:Receptors, Cholinergic; D000077339:Leflunomide