Therapeutic trial with protease inhibitor (leupeptin) in chicken muscular dystrophy. A histologic and histochemical study.

For the purpose of observing the therapeutic benefit of protease inhibitors for progressive muscular dystrophy, a large quantity of doses of leupeptin of 10 mg/kg/day and 50 mg/kg/day were administered i.p. to male chickens afflicted with hereditary muscular dystrophy (line 413) for 4 months starting on the 7th day ex ovo. No clinical improvement was identified in physical ability as a result of the examination by flip test, and creatine kinase (CK) values. The number of necrotic fibers in the pectoralis superficialis (PS) muscle which is known to be preferentially damaged in dystrophic chicken, did not decrease significantly in the birds treated with 10 mg leupeptin/kg/day (number of necrotic fibers; 47.7/mm2) and 50 mg/kg/day (46.4/mm2) as compared to that of the untreated ones (43.2/mm2). A morphometric analysis of fiber diameter distribution also showed no statistical difference between the treated and untreated birds. In the second group, 10 mg leupeptin/kg and a combination of leupeptin and bestatin of 10 mg/kg each were injected directly into the left lower half of the PS muscle three times a week for 4 months. Necrotic fibers were still present in the injected site, remote area of the left upper PS muscle treated with leupeptin (52.7/mm2), leupeptin and bestatin (52.2/mm2), and contralateral right upper PS muscle (41.6 and 53.5/mm2, respectively). The number of necrotic fibers in treated muscles was again not significantly different from that in untreated dystrophic ones (39.6/mm2). In fiber diameter analysis, no statistical difference was recognized between the treated and untreated dystrophic muscles.