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. 1981 Dec;78(12):7742–7744. doi: 10.1073/pnas.78.12.7742

Successful treatment of murine muscular dystrophy with the proteinase inhibitor leupeptin.

J H Sher, A Stracher, S A Shafiq, J Hardy-Stashin
PMCID: PMC349346  PMID: 6950412

Abstract

Mice with genetic muscular dystrophy were treated with intraperitoneal injections of the proteinase inhibitor leupeptin, beginning before the onset of weakness. A significant number of the treated animals failed to develop histological evidence of dystrophy, compared with controls. Leupeptin treatment prevented (or delayed) the onset of muscular dystrophy in this experiment.

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Selected References

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  1. Busch W. A., Stromer M. H., Goll D. E., Suzuki A. Ca 2+ -specific removal of Z lines from rabbit skeletal muscle. J Cell Biol. 1972 Feb;52(2):367–381. doi: 10.1083/jcb.52.2.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Costello B. R., Shafiq S. A. Freeze-fracture study of muscle plasmalemma in normal and dystrophic chickens. Muscle Nerve. 1979 May-Jun;2(3):191–201. doi: 10.1002/mus.880020307. [DOI] [PubMed] [Google Scholar]
  3. Enomoto A., Bradley W. G. Therapeutic trials in muscular dystrophy. III. Studies of microbial proteinase inhibitors in murine dystrophy. Arch Neurol. 1977 Dec;34(12):771–773. doi: 10.1001/archneur.1977.00500240059010. [DOI] [PubMed] [Google Scholar]
  4. Huston R. B., Krebs E. G. Activation of skeletal muscle phosphorylase kinase by Ca2+. II. Identification of the kinase activating factor as a proteolytic enzyme. Biochemistry. 1968 Jun;7(6):2116–2122. doi: 10.1021/bi00846a014. [DOI] [PubMed] [Google Scholar]
  5. Iodice A. A., Chin J., Perker S., Weinstock I. M. Cathepsins A, B, C, D and autolysis during development of breast muscle of normal and dystrophic chickens. Arch Biochem Biophys. 1972 Sep;152(1):166–174. doi: 10.1016/0003-9861(72)90204-4. [DOI] [PubMed] [Google Scholar]
  6. Ionasescu V., Ionasescu R., White D., Feld R., Cancilla P., Kaeding L., Kraus L., Stern L. Altered protein synthesis and creatine kinase in breast muscle cell cultures from dystrophic chick embryos. J Neurol Sci. 1980 May;46(2):157–168. doi: 10.1016/0022-510x(80)90074-x. [DOI] [PubMed] [Google Scholar]
  7. Libby P., Goldberg A. L. Leupeptin, a protease inhibitor, decreases protein degradation in normal and diseased muscles. Science. 1978 Feb 3;199(4328):534–536. doi: 10.1126/science.622552. [DOI] [PubMed] [Google Scholar]
  8. McGowan E. B., Shafiq S. A., Stracher A. Delayed degeneration of dystrophic and normal muscle cell cultures treated with pepstatin, leupeptin, and antipain. Exp Neurol. 1976 Mar;50(3):649–657. doi: 10.1016/0014-4886(76)90034-0. [DOI] [PubMed] [Google Scholar]
  9. Meier H., Southard J. L. Muscular dystrophy in the mouse caused by an allele at the dy-locus. Life Sci. 1970 Feb 8;9(3):137–144. doi: 10.1016/0024-3205(70)90306-1. [DOI] [PubMed] [Google Scholar]
  10. Mendell J. R., Higgins R., Sahenk Z., Cosmos E. Relevance of genetic animal models of muscular dystrophy to human muscular dystrophies. Ann N Y Acad Sci. 1979;317:409–430. [PubMed] [Google Scholar]
  11. Mokri B., Engel A. G. Duchenne dystrophy: electron microscopic findings pointing to a basic or early abnormality in the plasma membrane of the muscle fiber. Neurology. 1975 Dec;25(12):1111–1120. doi: 10.1212/wnl.25.12.1111. [DOI] [PubMed] [Google Scholar]
  12. Oberc M. A., Engel W. K. Ultrastructural localization of calcium in normal and abnormal skeletal muscle. Lab Invest. 1977 Jun;36(6):566–577. [PubMed] [Google Scholar]
  13. Pearson C. M., Kar N. C. Muscle breakdown and lysosomal activation (biochemistry). Ann N Y Acad Sci. 1979;317:465–477. doi: 10.1111/j.1749-6632.1979.tb56562.x. [DOI] [PubMed] [Google Scholar]
  14. Pennington R. J. Biochemistry of dystrophic muscle. 2. Some enzyme changes in dystrophic mouse muscle. Biochem J. 1963 Jul;88(1):64–68. doi: 10.1042/bj0880064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reddy M. K., Etlinger J. D., Rabinowitz M., Fischman D. A., Zak R. Removal of Z-lines and alpha-actinin from isolated myofibrils by a calcium-activated neutral protease. J Biol Chem. 1975 Jun 10;250(11):4278–4284. [PubMed] [Google Scholar]
  16. Rowland L. P. Biochemistry of muscle membranes in Duchenne muscular dystrophy. Muscle Nerve. 1980 Jan-Feb;3(1):3–20. doi: 10.1002/mus.880030103. [DOI] [PubMed] [Google Scholar]
  17. Schorr E. E., Arnason B. G., Aström K. E., Darzynkiewicz Z. Treatment of mouse muscular dystrophy with the protease inhibitor pepstatin. J Neuropathol Exp Neurol. 1978 May;37(3):263–268. doi: 10.1097/00005072-197805000-00004. [DOI] [PubMed] [Google Scholar]
  18. Stracher A., McGowan E. B., Shafiq S. A. Muscular dystrophy: inhibition of degeneration in vivo with protease inhibitors. Science. 1978 Apr 7;200(4337):50–51. doi: 10.1126/science.635570. [DOI] [PubMed] [Google Scholar]
  19. Stracher A., McGowan E. B., Siemankowski L., Molak V., Shafiq S. A. Relationship between myosin structure and muscle degeneration. Ann N Y Acad Sci. 1979;317:349–355. doi: 10.1111/j.1749-6632.1979.tb56546.x. [DOI] [PubMed] [Google Scholar]
  20. WEINSTOCK I. M., EPSTEIN S., MILHORAT A. T. Enzyme studies in muscular dystrophy. III. In hereditary muscular dystrophy in mice. Proc Soc Exp Biol Med. 1958 Oct;99(1):272–276. doi: 10.3181/00379727-99-24320. [DOI] [PubMed] [Google Scholar]

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