Treatment of experimental autoimmune myasthenia gravis in rabbits with leupeptin, a protease inhibitor.
We injected 12 New Zealand white rabbits intraperitoneally with 15 mg/kg Leupeptin on alternative days for about 4 months. After 1 week of Leupeptin treatment, they were challenged with purified acetylcholine receptor (AChR) from Torpedo californica in Freund's complete adjuvant. All control animals died within 60 days. Six animals treated with Leupeptin did not develop EAMG in spite of repeated AChR injections. Three animals developed clinical signs of EAMG after 65 days. The clinical course was short in the one that survived and prolonged in the 2 that finally died. All animals (Leupeptin-treated and controls) had circulating anti-AChR antibodies. Among the survivors, titers were slightly lower and EMG repetitive stimulation tests were normal. Leupeptin (0.02-200 mM) did not prevent curaremimetic [3H]toxin binding to AChR in membranes or in solution, nor dissociate AChR-toxin-antibody complexes. Immune response to antigens other than receptor remained intact in Leupeptin-treated animals. Leupeptin was not toxic at the doses given. The mechanism of this protection is not well understood. Leupeptin seems to decelerate the turnover rate of AChR induced by anti-AChR antibodies and/or to decrease the complement-mediated immune attack against the muscle end-plate.
Valderrama
R
R
Department of Neurology, SUNY Health Sciences Center, Brooklyn 11203.
Chang
V K
VK
Stracher
A
A
Maccabee
P J
PJ
Kaldany
R R
RR
D000818:Animals; D000906:Antibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000188:drug therapy*; D007976:Leupeptins / Q000627:therapeutic use*; D008297:Male; D009157:Myasthenia Gravis / Q000188:drug therapy* / Q000276:immunology; D009842:Oligopeptides / Q000627:therapeutic use*; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000276:immunology
D000906:Antibodies; D007976:Leupeptins; D009842:Oligopeptides; D011950:Receptors, Cholinergic; C032854:leupeptin