Delay of muscle degeneration and necrosis in mdx mice by calpain inhibition.
Inhibition of muscle degeneration by the tripeptide calpain inhibitor, leupeptin, was tested in vivo in a dystrophin-deficient mdx murine model. In a short-term control study, intramuscular administration of leupeptin for 30 days inhibited muscle degeneration as assessed by histologic analysis. Calpain inhibition could be correlated with retention of myofiber size and our results suggest that this may be a promising treatment modality in human Duchenne muscular dystrophy.
Badalamente
M A
MA
Department of Orthopedics, Health Science Center, State University of New York at Stony Brook, Stony Brook, New York, USA.
Stracher
A
A
D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use*; D006651:Histocytochemistry; D007976:Leupeptins / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008854:Microscopy, Electron; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D009336:Necrosis
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D002154:Calpain; C032854:leupeptin