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Annual Review of Genomics and Human Genetics

Volume 16, 2015

The Pathogenesis and Therapy of Muscular Dystrophies

Abstract

Current molecular genomic approaches to human genetic disorders have led to an explosion in the identification of the genes and their encoded proteins responsible for these disorders. The identification of the gene altered by mutations in Duchenne and Becker muscular dystrophy was one of the earliest examples of this paradigm. The nearly 30 years of research partly outlined here exemplifies the road that similar current gene discovery protocols will be expected to travel, albeit much more rapidly owing to improved diagnosis of genetic disorders and an understanding of the spectrum of mutations thought to cause them. The identification of the protein dystrophin has led to a new understanding of the muscle cell membrane and the proteins involved in membrane stability, as well as new candidate genes for additional forms of muscular dystrophy. Animal models identified with naturally occurring mutations and developed by genetic manipulation have furthered the understanding of disease progression and underlying pathology. The biochemistry and molecular analysis of patient samples have led to the different dystrophin-dependent and -independent therapies that are currently close to or in human clinical trials. The lessons learned from decades of research on dystrophin have benefited the field of human genetics.

Keyword(s): clinical trials, DMD, muscle, muscular dystrophy, therapy
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2015-08-24
2024-04-19
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Literature Cited

  1. Aartsma-Rus A. 1.  2014. Dystrophin analysis in clinical trials. J. Neuromusc. Dis. 1:41–53 [Google Scholar]
  2. Aartsma-Rus A, Ferlini A, Goemans N, Pasmooij AM, Wells DJ. 2.  et al. 2014. Translational and regulatory challenges for exon skipping therapies. Hum. Gene Ther. 25:885–92 [Google Scholar]
  3. Aartsma-Rus A, Ferlini A, Vroom E. 3.  2014. Biomarkers and surrogate endpoints in Duchenne: meeting report. Neuromusc. Disord. 24:743–45 [Google Scholar]
  4. Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J. 4.  et al. 2009. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum. Mutat. 30:293–99 [Google Scholar]
  5. Aartsma-Rus A, Janson AA, Kaman WE, Bremmer-Bout M, van Ommen GJB. 5.  et al. 2004. Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense. Am. J. Hum. Genet. 74:83–92 [Google Scholar]
  6. Adamo CM, Dai DF, Percival JM, Minami E, Willis MS. 6.  et al. 2010. Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy. PNAS 107:19079–83 [Google Scholar]
  7. Amenta AR, Yilmaz A, Bogdanovich S, McKechnie BA, Abedi M. 7.  et al. 2011. Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice. PNAS 108:762–67 [Google Scholar]
  8. Angus LM, Chakkalakal JV, Mejat A, Eibl JK, Belanger G. 8.  et al. 2005. Calcineurin-NFAT signaling, together with GABP and peroxisome PGC-1α, drives utrophin gene expression at the neuromuscular junction. Am. J. Physiol. Cell Physiol. 289:C908–17 [Google Scholar]
  9. Arahata K, Ishiura S, Ishiguro T, Tsukahara T, Suhara Y. 9.  et al. 1988. Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide. Nature 333:861–63 [Google Scholar]
  10. Arpan I, Willcocks RJ, Forbes SC, Finkel RS, Lott DJ. 10.  et al. 2014. Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS. Neurology 83:974–80 [Google Scholar]
  11. Athanasopoulos T, Graham IR, Foster H, Dickson G. 11.  2004. Recombinant adeno-associated viral (rAAV) vectors as therapeutic tools for Duchenne muscular dystrophy (DMD). Gene Ther. 11:Suppl. 1S109–21 [Google Scholar]
  12. Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM. 12.  et al. 2013. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve 47:416–23 [Google Scholar]
  13. Ayalon G, Davis JQ, Scotland PB, Bennett V. 13.  2008. An ankyrin-based mechanism for functional organization of dystrophin and dystroglycan. Cell 135:1189–200 [Google Scholar]
  14. Bakker E, Goor N, Wrogemann K, Kunkel LM, Fenton WA. 14.  et al. 1985. Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs. Lancet 325:655–58 [Google Scholar]
  15. Bakker E, Van Broeckhoven C, Bonten EJ, van de Vooren MJ, Veenema H. 15.  et al. 1987. Germline mosaicism and Duchenne muscular dystrophy mutations. Nature 329:554–56 [Google Scholar]
  16. Balasubramanian S, Fung ET, Huganir RL. 16.  1998. Characterization of the tyrosine phosphorylation and distribution of dystrobrevin isoforms. FEBS Lett. 432:133–40 [Google Scholar]
  17. Banks GB, Combs AC, Odom GL, Bloch RJ, Chamberlain JS. 17.  2014. Muscle structure influences utrophin expression in mdx mice. PLOS Genet. 10:e1004431 [Google Scholar]
  18. Bartoli M, Poupiot J, Vulin A, Fougerousse F, Arandel L. 18.  et al. 2007. AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency. Gene Ther. 14:733–40 [Google Scholar]
  19. Barton ER, Morris L, Musaro A, Rosenthal N, Sweeney HL. 19.  2002. Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. J. Cell Biol. 157:137–48 [Google Scholar]
  20. Bassett DI, Currie PD. 20.  2003. The zebrafish as a model for muscular dystrophy and congenital myopathy. Hum. Mol. Genet. 12:Suppl. 2R265–70 [Google Scholar]
  21. Belanto JJ, Mader TL, Eckhoff MD, Strandjord DM, Banks GB. 21.  et al. 2014. Microtubule binding distinguishes dystrophin from utrophin. PNAS 111:5723–28 [Google Scholar]
  22. Bessou C, Giugia J-B, Franks CJ, Holden-Dye L, Ségalat L. 22.  1998. Mutations in the Caenorhabditis elegans dystrophin-like gene dys-1 lead to hyperactivity and suggest a link with cholinergic transmission. Neurogenetics 2:61–72 [Google Scholar]
  23. Betts C, Saleh AF, Arzumanov AA, Hammond SM, Godfrey C. 23.  et al. 2012. Pip6-PMO, a new generation of peptide-oligonucleotide conjugates with improved cardiac exon skipping activity for DMD treatment. Mol. Ther. Nucleic Acids 1:e38 [Google Scholar]
  24. Bish LT, Sleeper MM, Forbes SC, Wang B, Reynolds C. 24.  et al. 2012. Long-term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping. Mol. Ther. 20:580–89 [Google Scholar]
  25. Bladen CL, Rafferty K, Straub V, Monges S, Moresco A. 25.  et al. 2013. The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia. Hum. Mutat. 34:1449–57 [Google Scholar]
  26. Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K. 26.  et al. 2015. The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum. Mutat. 36:395–402 [Google Scholar]
  27. Blake DJ, Love DR, Tinsley J, Morris GE, Turley H. 27.  et al. 1992. Characterization of a 4.8kb transcript from the Duchenne muscular dystrophy locus expressed in Schwannoma cells. Hum. Mol. Genet. 1:103–9 [Google Scholar]
  28. Bogdanovich S, Krag TO, Barton ER, Morris LD, Whittemore LA. 28.  et al. 2002. Functional improvement of dystrophic muscle by myostatin blockade. Nature 420:418–21 [Google Scholar]
  29. Bonilla E, Samitt CE, Miranda AF, Hays AP, Salviati G. 29.  et al. 1988. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 54:447–52 [Google Scholar]
  30. Botstein D, White RL, Skolnick M, Davis RW. 30.  1980. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32:314–31 [Google Scholar]
  31. Bowe MA, Mendis DB, Fallon JR. 31.  2000. The small leucine-rich repeat proteoglycan biglycan binds to α-dystroglycan and is upregulated in dystrophic muscle. J. Cell Biol. 148:801–10 [Google Scholar]
  32. Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ. 32.  et al. 2012. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol. Ther. 20:443–55 [Google Scholar]
  33. Boyd Y, Buckle V, Holt S, Munro E, Hunter D, Craig I. 33.  1986. Muscular dystrophy in girls with X;autosome translocations. J. Med. Genet. 23:484–90 [Google Scholar]
  34. Bredt DS, Snyder SH. 34.  1994. Nitric oxide: a physiologic messenger molecule. Annu. Rev. Biochem. 63:175–95 [Google Scholar]
  35. Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE. 35.  et al. 1996. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and α1-syntrophin mediated by PDZ domains. Cell 84:757–67 [Google Scholar]
  36. Brenman JE, Chao DS, Xia H, Aldape K, Bredt DS. 36.  1995. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82:743–52 [Google Scholar]
  37. Brunelli S, Sciorati C, D'Antona G, Innocenzi A, Covarello D. 37.  et al. 2007. Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy. PNAS 104:264–69 [Google Scholar]
  38. Bulfield G, Siller WG, Wight PAL, Moore KJ. 38.  1984. X chromosome-linked muscular dystrophy (mdx) in the mouse. PNAS 81:1189–92 [Google Scholar]
  39. Burghes AH, Logan C, Hu X, Belfall B, Worton RG, Ray PN. 39.  1987. A cDNA clone from the Duchenne/Becker muscular dystrophy gene. Nature 328:434–37 [Google Scholar]
  40. Burkin DJ, Wallace GQ, Milner DJ, Chaney EJ, Mulligan JA, Kaufman SJ. 40.  2005. Transgenic expression of α7β1 integrin maintains muscle integrity, increases regenerative capacity, promotes hypertrophy, and reduces cardiomyopathy in dystrophic mice. Am. J. Pathol. 166:253–63 [Google Scholar]
  41. Burkin DJ, Wallace GQ, Nicol KJ, Kaufman DJ, Kaufman SJ. 41.  2001. Enhanced expression of the α7β1 integrin reduces muscular dystrophy and restores viability in dystrophic mice. J. Cell Biol. 152:1207–18 [Google Scholar]
  42. Burmeister M, Lehrach H. 42.  1986. Long-range restriction map around the Duchenne muscular dystrophy gene. Nature 324:582–85 [Google Scholar]
  43. Burton EA, Tinsley JM, Holzfeind PJ, Rodrigues NR, Davies KE. 43.  1999. A second promoter provides an alternative target for therapeutic up-regulation of utrophin in Duchenne muscular dystrophy. PNAS 96:14025–30 [Google Scholar]
  44. Bushby K, Finkel R, Wong B, Barohn R, Campbell C. 44.  et al. 2014. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve 50:477–87 [Google Scholar]
  45. Bushby K, Muntoni F, Urtizberea A, Hughes R, Griggs R. 45.  2004. Report on the 124th ENMC International Workshop. Treatment of Duchenne muscular dystrophy; defining the gold standards of management in the use of corticosteroids. 2–4 April 2004, Naarden, The Netherlands. Neuromusc. Disord. 14:526–34 [Google Scholar]
  46. Call JA, Ervasti JM, Lowe DA. 46.  2011. TAT-μUtrophin mitigates the pathophysiology of dystrophin and utrophin double-knockout mice. J. Appl. Physiol. 111:200–5 [Google Scholar]
  47. Campbell KP, Kahl SD. 47.  1989. Association of dystrophin and an integral membrane glycoprotein. Nature 338:259–62 [Google Scholar]
  48. Casar JC, McKechnie BA, Fallon JR, Young MF, Brandan E. 48.  2004. Transient up-regulation of biglycan during skeletal muscle regeneration: delayed fiber growth along with decorin increase in biglycan-deficient mice. Dev. Biol. 268:358–71 [Google Scholar]
  49. Cerletti M, Negri T, Cozzi F, Colpo R, Andreetta F. 49.  et al. 2003. Dystrophic phenotype of canine X-linked muscular dystrophy is mitigated by adenovirus-mediated utrophin gene transfer. Gene Ther. 10:750–57 [Google Scholar]
  50. Chakkalakal JV, Stocksley MA, Harrison MA, Angus LM, Deschenes-Furry J. 50.  et al. 2003. Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling. PNAS 100:7791–96 [Google Scholar]
  51. Chakravarty D, Chakraborti S, Chakrabarti P. 51.  2015. Flexibility in the N-terminal actin-binding domain: clues from in silico mutations and molecular dynamics. Proteins 83:696–710 [Google Scholar]
  52. Chamberlain JS, Metzger J, Reyes M, Townsend D, Faulkner JA. 52.  2007. Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma. FASEB J. 21:2195–204 [Google Scholar]
  53. Chancellor DR, Davies KE, De Moor O, Dorgan CR, Johnson PD. 53.  et al. 2011. Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of Duchenne muscular dystrophy. J. Med. Chem. 54:3241–50 [Google Scholar]
  54. Chandrasekharan K, Yoon JH, Xu Y, deVries S, Camboni M. 54.  et al. 2010. A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy. Sci. Transl. Med. 2:42ra54 [Google Scholar]
  55. Chicoine LG, Rodino-Klapac LR, Shao G, Xu R, Bremer WG. 55.  et al. 2014. Vascular delivery of rAAVrh74.MCK.GALGT2 to the gastrocnemius muscle of the rhesus macaque stimulates the expression of dystrophin and laminin α2 surrogates. Mol. Ther. 22:713–24 [Google Scholar]
  56. Clarkson PM, Hubal MJ. 56.  2002. Exercise-induced muscle damage in humans. Am. J. Phys. Med. Rehabil. 81:S52–69 [Google Scholar]
  57. Connolly AM, Keeling RM, Mehta S, Pestronk A, Sanes JR. 57.  2001. Three mouse models of muscular dystrophy: the natural history of strength and fatigue in dystrophin-, dystrophin/utrophin-, and laminin α2-deficient mice. Neuromusc. Disord. 11:703–12 [Google Scholar]
  58. Connolly AM, Schierbecker J, Renna R, Florence J. 58.  2002. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromusc. Disord. 12:917–25 [Google Scholar]
  59. Consolino CM, Brooks SV. 59.  2004. Susceptibility to sarcomere injury induced by single stretches of maximally activated muscles of mdx mice. J. Appl. Physiol. 96:633–38 [Google Scholar]
  60. Cooper BJ, Winand NJ, Stedman H, Valentine BA, Hoffman EP. 60.  et al. 1988. The homologue of the Duchenne locus is defective in X-linked muscular dystrophy of dogs. Nature 334:154–56 [Google Scholar]
  61. Cox GA, Phelps SF, Chapman VM, Chamberlain JS. 61.  1993. New mdx mutation disrupts expression of muscle and nonmuscle isoforms of dystrophin. Nat. Genet. 4:87–93 [Google Scholar]
  62. Crosbie RH, Lim LE, Moore SA, Hirano M, Hays AP. 62.  et al. 2000. Molecular and genetic characterization of sarcospan: insights into sarcoglycan-sarcospan interactions. Hum. Mol. Genet. 9:2019–27 [Google Scholar]
  63. Crosbie RH, Straub V, Yun HY, Lee JC, Rafael JA. 63.  et al. 1998. mdx muscle pathology is independent of nNOS perturbation. Hum. Mol. Genet. 7:823–29 [Google Scholar]
  64. Dalkilic I, Kunkel LM. 64.  2003. Muscular dystrophies: genes to pathogenesis. Curr. Opin. Genet. Dev. 13:231–38 [Google Scholar]
  65. Damsker JM, Dillingham BC, Rose MC, Balsley MA, Heier CR. 65.  et al. 2013. VBP15, a glucocorticoid analogue, is effective at reducing allergic lung inflammation in mice. PLOS ONE 8:e63871 [Google Scholar]
  66. Davies KE, Pearson PL, Harper PS, Murray JM, O'Brien T. 66.  et al. 1983. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. Nucleic Acids Res. 11:2303–12 [Google Scholar]
  67. Deconinck AE, Rafael JA, Skinner JA, Brown SC, Potter AC. 67.  et al. 1997. Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 90:717–27 [Google Scholar]
  68. Deconinck N, Tinsley J, De Backer F, Fisher R, Kahn D. 68.  et al. 1997. Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice. Nat. Med. 3:1216–21 [Google Scholar]
  69. Duan D. 69.  2015. Duchenne muscular dystrophy gene therapy in the canine model. Hum. Gene Ther. Clin. Dev. 2657–69
  70. Emery A. 70.  1988. Duchenne Muscular Dystrophy Oxford, UK: Oxford Univ. Press
  71. England SB, Nicholson LV, Johnson MA, Forrest SM, Love DR. 71.  et al. 1990. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 343:180–82 [Google Scholar]
  72. Ervasti JM, Campbell KP. 72.  1991. Membrane organization of the dystrophin-glycoprotein complex. Cell 66:1121–31 [Google Scholar]
  73. Ervasti JM, Campbell KP. 73.  1993. A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. J. Cell Biol. 122:809–23 [Google Scholar]
  74. Ervasti JM, Ohlendieck K, Kahl SD, Gaver MG, Campbell KP. 74.  1990. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature 345:315–19 [Google Scholar]
  75. Fairclough RJ, Perkins KJ, Davies KE. 75.  2012. Pharmacologically targeting the primary defect and downstream pathology in Duchenne muscular dystrophy. Curr. Gene Ther. 12:206–44 [Google Scholar]
  76. Fan Y, Maley M, Beilharz M, Grounds M. 76.  1996. Rapid death of injected myoblasts in myoblast transfer therapy. Muscle Nerve 19:853–60 [Google Scholar]
  77. Fan Z, Kocis K, Valley R, Howard JF, Chopra M. 77.  et al. 2012. Safety and feasibility of high-pressure transvenous limb perfusion with 0.9% saline in human muscular dystrophy. Mol. Ther. 20:456–61 [Google Scholar]
  78. Ferlini A, Flanigan KM, Lochmuller H, Muntoni F, 't Hoen PAC, McNally E. 78.  2015. 204th ENMC International Workshop on Biomarkers in Duchenne Muscular Dystrophy 24–26 January 2014, Naarden, The Netherlands. Neuromusc. Disord. 25:184–98 [Google Scholar]
  79. Finkel RS, Flanigan KM, Wong B, Bonnemann C, Sampson J. 79.  et al. 2013. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLOS ONE 8:e81302 [Google Scholar]
  80. Fisher R, Tinsley JM, Phelps SR, Squire SE, Townsend ER. 80.  et al. 2001. Non-toxic ubiquitous over-expression of utrophin in the mdx mouse. Neuromusc. Disord. 11:713–21 [Google Scholar]
  81. Forrest SM, Cross GS, Speer A, Gardner-Medwin D, Burn J, Davies KE. 81.  1987. Preferential deletion of exons in Duchenne and Becker muscular dystrophies. Nature 329:638–40 [Google Scholar]
  82. Francke U, Ochs HD, de Martinville B, Giacalone J, Lindgren V. 82.  et al. 1985. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. Am. J. Hum. Genet. 37:250–67 [Google Scholar]
  83. Gawlik KI, Oliveira BM, Durbeej M. 83.  2011. Transgenic expression of laminin α1 chain does not prevent muscle disease in the mdx mouse model for Duchenne muscular dystrophy. Am. J. Pathol. 178:1728–37 [Google Scholar]
  84. Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF. 84.  et al. 2011. Systemic administration of PRO051 in Duchenne's muscular dystrophy. N. Engl. J. Med. 364:1513–22 [Google Scholar]
  85. Goyenvalle A, Griffith G, Babbs A, Andaloussi SE, Ezzat K. 85.  et al. 2015. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat. Med. 21:270–75 [Google Scholar]
  86. Goyenvalle A, Vulin A, Fougerousse F, Leturcq F, Kaplan JC. 86.  et al. 2004. Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 306:1796–99 [Google Scholar]
  87. Greener MJ, Roberts RG. 87.  2000. Conservation of components of the dystrophin complex in Drosophila. FEBS Lett. 482:13–18 [Google Scholar]
  88. Gregorevic P, Blankinship MJ, Allen JM, Crawford RW, Meuse L. 88.  et al. 2004. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat. Med. 10:828–34 [Google Scholar]
  89. Griggs RC, Herr BE, Reha A, Elfring G, Atkinson L. 89.  et al. 2013. Corticosteroids in Duchenne muscular dystrophy: major variations in practice. Muscle Nerve 48:27–31 [Google Scholar]
  90. Grounds MD. 90.  2008. Two-tiered hypotheses for Duchenne muscular dystrophy. Cell Mol. Life Sci. 65:1621–25 [Google Scholar]
  91. Grounds MD, Torrisi J. 91.  2004. Anti-TNFα (Remicade) therapy protects dystrophic skeletal muscle from necrosis. FASEB J. 18:676–82 [Google Scholar]
  92. Grozdanovic Z, Baumgarten HG. 92.  1999. Nitric oxide synthase in skeletal muscle fibers: a signaling component of the dystrophin-glycoprotein complex. Histol. Histopathol. 14:243–56 [Google Scholar]
  93. Guiraud S, Squire SE, Edwards B, Chen H, Burns DT. 93.  et al. 2015. Second-generation compound for the modulation of utrophin in the therapy of DMD. Hum. Mol. Genet. 244212–24
  94. Guiraud S, van Wittenberghe L, Georger C, Scherman D, Kichler A. 94.  2012. Identification of decorin derived peptides with a zinc dependent anti-myostatin activity. Neuromusc. Disord. 22:1057–68 [Google Scholar]
  95. Guo C, Willem M, Werner A, Raivich G, Emerson M. 95.  et al. 2006. Absence of α7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy. Hum. Mol. Genet. 15:989–98 [Google Scholar]
  96. Gupta V, Kawahara G, Gundry SR, Chen AT, Lencer WI. 96.  et al. 2011. The zebrafish dag1 mutant: a novel genetic model for dystroglycanopathies. Hum. Mol. Genet. 20:1712–25 [Google Scholar]
  97. Gurpur PB, Liu J, Burkin DJ, Kaufman SJ. 97.  2009. Valproic acid activates the PI3K/Akt/mTOR pathway in muscle and ameliorates pathology in a mouse model of Duchenne muscular dystrophy. Am. J. Pathol. 174:999–1008 [Google Scholar]
  98. Haas M, Vlcek V, Balabanov P, Salmonson T, Bakchine S. 98.  et al. 2015. European Medicines Agency review of ataluren for the treatment of ambulant patients aged 5 years and older with Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene. Neuromusc. Disord. 25:5–13 [Google Scholar]
  99. Haidet AM, Rizo L, Handy C, Umapathi P, Eagle A. 99.  et al. 2008. Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. PNAS 105:4318–22 [Google Scholar]
  100. Heier CR, Damsker JM, Yu Q, Dillingham BC, Huynh T. 100.  et al. 2013. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol. Med. 5:1569–85 [Google Scholar]
  101. Heller KN, Montgomery CL, Shontz KM, Clark KR, Mendell JR, Rodino-Klapac LR. 101.  2014. Human a7 integrin gene (ITGA7) delivered by adeno-associated virus reverses the phenotype of the double knock out (DKO) mouse devoid of dystrophin and utrophin Presented at Int. World Muscle Soc. Congr., 19th, Berlin, Oct. 7–11 [Google Scholar]
  102. Helliwell TR, Man NT, Morris GE, Davies KE. 102.  1992. The dystrophin-related protein, utrophin, is expressed on the sarcolemma of regenerating human skeletal muscle fibres in dystrophies and inflammatory myopathies. Neuromusc. Disord. 2:177–84 [Google Scholar]
  103. Hodges BL, Hayashi YK, Nonaka I, Wang W, Arahata K, Kaufman SJ. 103.  1997. Altered expression of the α7β1 integrin in human and murine muscular dystrophies. J. Cell Sci. 110:2873–81 [Google Scholar]
  104. Hoffman EP, Brown RH Jr, Kunkel LM. 104.  1987. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–28 [Google Scholar]
  105. Hoffman EP, Knudson CM, Campbell KP, Kunkel LM. 105.  1987. Subcellular fractionation of dystrophin to the triads of skeletal muscle. Nature 330:754–58 [Google Scholar]
  106. Hosoyama T, McGivern JV, Van Dyke JM, Ebert AD, Suzuki M. 106.  2014. Derivation of myogenic progenitors directly from human pluripotent stem cells using a sphere-based culture. Stem Cells Transl. Med. 3:564–74 [Google Scholar]
  107. Huang X, Poy F, Zhang R, Joachimiak A, Sudol M, Eck MJ. 107.  2000. Structure of a WW domain containing fragment of dystrophin in complex with β-dystroglycan. Nat. Struct. Biol. 7:634–38 [Google Scholar]
  108. Hynes RO. 108.  1992. Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25 [Google Scholar]
  109. Ibraghimov-Beskrovnaya O, Ervasti JM, Leveille CJ, Slaughter CA, Sernett SW, Campbell KP. 109.  1992. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature 355:696–702 [Google Scholar]
  110. Ibraghimov-Beskrovnaya O, Milatovich A, Ozcelik T, Yang B, Koepnick K. 110.  et al. 1993. Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization. Hum. Mol. Genet. 2:1651–57 [Google Scholar]
  111. Ingalls CP, Warren GL, Williams JH, Ward CW, Armstrong RB. 111.  1998. E-C coupling failure in mouse EDL muscle after in vivo eccentric contractions. J. Appl. Physiol. 85:58–67 [Google Scholar]
  112. Ishikawa Y, Miura T, Aoyagi T, Ogata H, Hamada S, Minami R. 112.  2011. Duchenne muscular dystrophy: survival by cardio-respiratory interventions. Neuromusc. Disord. 21:47–51 [Google Scholar]
  113. Ishikawa-Sakurai M, Yoshida M, Imamura M, Davies KE, Ozawa E. 113.  2004. ZZ domain is essentially required for the physiological binding of dystrophin and utrophin to beta-dystroglycan. Hum. Mol. Genet. 13:693–702 [Google Scholar]
  114. Jarver P, O'Donovan L, Gait MJ. 114.  2014. A chemical view of oligonucleotides for exon skipping and related drug applications. Nucleic Acid Ther. 24:37–47 [Google Scholar]
  115. Judge LM, Arnett AL, Banks GB, Chamberlain JS. 115.  2011. Expression of the dystrophin isoform Dp116 preserves functional muscle mass and extends lifespan without preventing dystrophy in severely dystrophic mice. Hum. Mol. Genet. 20:4978–90 [Google Scholar]
  116. Kawahara G, Karpf JA, Myers JA, Alexander MS, Guyon JR, Kunkel LM. 116.  2011. Drug screening in a zebrafish model of Duchenne muscular dystrophy. PNAS 108:5331–36 [Google Scholar]
  117. Kenwrick S, Patterson M, Speer A, Fischbeck K, Davies KE. 117.  1987. Molecular analysis of the Duchenne muscular dystrophy region using pulsed field gel electrophoresis. Cell 48:351–57 [Google Scholar]
  118. Khairallah M, Khairallah RJ, Young ME, Allen BG, Gillis MA. 118.  et al. 2008. Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. PNAS 105:7028–33 [Google Scholar]
  119. Khurana TS, Hoffman EP, Kunkel LM. 119.  1990. Identification of a chromosome 6-encoded dystrophin-related protein. J. Biol. Chem. 265:16717–20 [Google Scholar]
  120. Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D. 120.  et al. 2009. Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 8:918–28 [Google Scholar]
  121. Kingston HM, Sarfarazi M, Thomas NS, Harper PS. 121.  1984. Localisation of the Becker muscular dystrophy gene on the short arm of the X chromosome by linkage to cloned DNA sequences. Hum. Genet. 67:6–17 [Google Scholar]
  122. Klietsch R, Ervasti JM, Arnold W, Campbell KP, Jorgensen AO. 122.  1993. Dystrophin-glycoprotein complex and laminin colocalize to the sarcolemma and transverse tubules of cardiac muscle. Circ. Res. 72:349–60 [Google Scholar]
  123. Klymiuk N, Blutke A, Graf A, Krause S, Burkhardt K. 123.  et al. 2013. Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle. Hum. Mol. Genet. 22:4368–82 [Google Scholar]
  124. Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K. 124.  et al. 1989. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am. J. Hum. Genet. 45:498–506 [Google Scholar]
  125. Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. 125.  1987. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50:509–17 [Google Scholar]
  126. Koenig M, Kunkel LM. 126.  1990. Detailed analysis of the repeat domain of dystrophin reveals four potential hinge segments that may confer flexibility. J. Biol. Chem. 265:4560–66 [Google Scholar]
  127. Koenig M, Monaco AP, Kunkel LM. 127.  1988. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53:219–28 [Google Scholar]
  128. Koo T, Wood MJ. 128.  2013. Clinical trials using antisense oligonucleotides in Duchenne muscular dystrophy. Hum. Gene Ther. 24:479–88 [Google Scholar]
  129. Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A. 129.  et al. 2009. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci. Transl. Med. 1:6ra15 [Google Scholar]
  130. Kotin RM. 130.  2011. Large-scale recombinant adeno-associated virus production. Hum. Mol. Genet. 20:R2–6 [Google Scholar]
  131. Krag TO, Bogdanovich S, Jensen CJ, Fischer MD, Hansen-Schwartz J. 131.  et al. 2004. Heregulin ameliorates the dystrophic phenotype in mdx mice. PNAS 101:13856–60 [Google Scholar]
  132. Kunkel LM, Hejtmancik JF, Caskey CT, Speer A, Monaco AP. 132.  et al. 1986. Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 322:73–77 [Google Scholar]
  133. Kunkel LM, Monaco AP, Middlesworth W, Ochs HD, Latt SA. 133.  1985. Specific cloning of DNA fragments absent from the DNA of a male patient with an X chromosome deletion. PNAS 82:4778–82 [Google Scholar]
  134. Lai Y, Thomas GD, Yue Y, Yang HT, Li D. 134.  et al. 2009. Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. J. Clin. Investig. 119:624–35 [Google Scholar]
  135. Lampen A, Siehler S, Ellerbeck U, Gottlicher M, Nau H. 135.  1999. New molecular bioassays for the estimation of the teratogenic potency of valproic acid derivatives in vitro: activation of the peroxisomal proliferator-activated receptor (PPARδ). Toxicol. Appl. Pharmacol. 160:238–49 [Google Scholar]
  136. Larcher T, Lafoux A, Tesson L, Remy S, Thepenier V. 136.  et al. 2014. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy. PLOS ONE 9:e110371 [Google Scholar]
  137. Le Guiner C, Montus M, Servais L, Cherel Y, Francois V. 137.  et al. 2014. Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients. Mol. Ther. 22:1923–35 [Google Scholar]
  138. Lee SJ, McPherron AC. 138.  2001. Regulation of myostatin activity and muscle growth. PNAS 98:9306–11 [Google Scholar]
  139. Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME. 139.  et al. 2005. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. PNAS 102:18117–22 [Google Scholar]
  140. Leung DG, Herzka DA, Thompson WR, He B, Bibat G. 140.  et al. 2014. Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy. Ann. Neurol. 76:541–49 [Google Scholar]
  141. Li D, Bareja A, Judge L, Yue Y, Lai Y. 141.  et al. 2010. Sarcolemmal nNOS anchoring reveals a qualitative difference between dystrophin and utrophin. J. Cell Sci. 123:2008–13 [Google Scholar]
  142. Li HL, Fujimoto N, Sasakawa N, Shirai S, Ohkame T. 142.  et al. 2015. Precise correction of the dystrophin gene in Duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9. Stem Cell Rep. 4:143–54 [Google Scholar]
  143. Liu J, Burkin DJ, Kaufman SJ. 143.  2008. Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression. Am. J. Physiol. Cell Physiol. 294:C627–40 [Google Scholar]
  144. Ljubicic V, Burt M, Jasmin BJ. 144.  2014. The therapeutic potential of skeletal muscle plasticity in Duchenne muscular dystrophy: phenotypic modifiers as pharmacologic targets. FASEB J. 28:548–68 [Google Scholar]
  145. Ljubicic V, Jasmin BJ. 145.  2013. AMP-activated protein kinase at the nexus of therapeutic skeletal muscle plasticity in Duchenne muscular dystrophy. Trends Mol. Med. 19:614–24 [Google Scholar]
  146. Ljubicic V, Miura P, Burt M, Boudreault L, Khogali S. 146.  et al. 2011. Chronic AMPK activation evokes the slow, oxidative myogenic program and triggers beneficial adaptations in mdx mouse skeletal muscle. Hum. Mol. Genet. 20:3478–93 [Google Scholar]
  147. Love DR, Hill DF, Dickson G, Spurr NK, Byth BC. 147.  et al. 1989. An autosomal transcript in skeletal muscle with homology to dystrophin. Nature 339:55–58 [Google Scholar]
  148. Luise M, Presotto C, Senter L, Betto R, Ceoldo S. 148.  et al. 1993. Dystrophin is phosphorylated by endogenous protein kinases. Biochem. J. 293:243–47 [Google Scholar]
  149. Madhavan R, Jarrett HW. 149.  1999. Phosphorylation of dystrophin and α-syntrophin by Ca2+-calmodulin dependent protein kinase II. Biochim. Biophys. Acta 1434:260–74 [Google Scholar]
  150. Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W. 150.  et al. 2010. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann. Neurol. 67:771–80 [Google Scholar]
  151. Mann CJ, Honeyman K, Cheng AJ, Ly T, Lloyd F. 151.  et al. 2001. Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse. PNAS 98:42–47 [Google Scholar]
  152. Martin EA, Barresi R, Byrne BJ, Tsimerinov EI, Scott BL. 152.  et al. 2012. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy. Sci. Transl. Med. 4:162ra55 [Google Scholar]
  153. Matsumura K, Ervasti JM, Ohlendieck K, Kahl SD, Campbell KP. 153.  1992. Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. Nature 360:588–91 [Google Scholar]
  154. Mayer U, Saher G, Fassler R, Bornemann A, Echtermeyer F. 154.  et al. 1997. Absence of integrin α7 causes a novel form of muscular dystrophy. Nat. Genet. 17:318–23 [Google Scholar]
  155. McGeachie JK, Grounds MD, Partridge TA, Morgan JE. 155.  1993. Age-related changes in replication of myogenic cells in mdx mice: quantitative autoradiographic studies. J. Neurol. Sci. 119:169–79 [Google Scholar]
  156. McGreevy JW, Hakim CH, McIntosh MA, Duan D. 156.  2015. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy. Dis. Models Mech. 8:195–213 [Google Scholar]
  157. McNeil PL, Khakee R. 157.  1992. Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage. Am. J. Pathol. 140:1097–109 [Google Scholar]
  158. McPherron AC, Lawler AM, Lee SJ. 158.  1997. Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 387:83–90 [Google Scholar]
  159. Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C. 159.  et al. 2010. Dystrophin immunity in Duchenne's muscular dystrophy. N. Engl. J. Med. 363:1429–37 [Google Scholar]
  160. Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM. 160.  et al. 1989. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N. Engl. J. Med. 320:1592–97 [Google Scholar]
  161. Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L. 161.  et al. 2013. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann. Neurol. 74:637–47 [Google Scholar]
  162. Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM. 162.  et al. 2015. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Mol. Ther. 23:192–201 [Google Scholar]
  163. Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R. 163.  et al. 2012. Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann. Neurol. 71:304–13 [Google Scholar]
  164. Mercado ML, Amenta AR, Hagiwara H, Rafii MS, Lechner BE. 164.  et al. 2006. Biglycan regulates the expression and sarcolemmal localization of dystrobrevin, syntrophin, and nNOS. FASEB J. 20:1724–26 [Google Scholar]
  165. Meregalli M, Farini A, Belicchi M, Parolini D, Cassinelli L. 165.  et al. 2013. Perspectives of stem cell therapy in Duchenne muscular dystrophy. FEBS J. 280:4251–62 [Google Scholar]
  166. Michalak M, Fu SY, Milner RE, Busaan JL, Hance JE. 166.  1996. Phosphorylation of the carboxyl-terminal region of dystrophin. Biochem. Cell Biol. 74:431–37 [Google Scholar]
  167. Milner RE, Busaan JL, Holmes CF, Wang JH, Michalak M. 167.  1993. Phosphorylation of dystrophin. The carboxyl-terminal region of dystrophin is a substrate for in vitro phosphorylation by p34cdc2 protein kinase. J. Biol. Chem. 268:21901–5 [Google Scholar]
  168. Miura P, Chakkalakal JV, Boudreault L, Belanger G, Hebert RL. 168.  et al. 2009. Pharmacological activation of PPARβ/δ stimulates utrophin A expression in skeletal muscle fibers and restores sarcolemmal integrity in mature mdx mice. Hum. Mol. Genet. 18:4640–49 [Google Scholar]
  169. Moens P, Baatsen PH, Marechal G. 169.  1993. Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch. J. Muscle Res. Cell Motil. 14:446–51 [Google Scholar]
  170. Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM. 170.  1988. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2:90–95 [Google Scholar]
  171. Monaco AP, Bertelson CJ, Middlesworth W, Colletti CA, Aldridge J. 171.  et al. 1985. Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment. Nature 316:842–45 [Google Scholar]
  172. Monaco AP, Neve RL, Colletti-Feener C, Bertelson CJ, Kurnit DM, Kunkel LM. 172.  1986. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 323:646–50 [Google Scholar]
  173. Moorwood C, Lozynska O, Suri N, Napper AD, Diamond SL, Khurana TS. 173.  2011. Drug discovery for Duchenne muscular dystrophy via utrophin promoter activation screening. PLOS ONE 6:e26169 [Google Scholar]
  174. Mulivor A, Cannell M, Davies M, Sako D, Liu J, Bresnahan D. 174.  et al. 2014. ACE-083, a ligand trap for members of the TGFβ superfamily, increases muscle mass locally in a mouse model of Duchenne muscular dystrophy Presented at Action Duchenne Int. Conf., 12th, London, Nov 7–8
  175. Nadarajah VD, van Putten M, Chaouch A, Garrood P, Straub V. 175.  et al. 2011. Serum matrix metalloproteinase-9 (MMP-9) as a biomarker for monitoring disease progression in Duchenne muscular dystrophy (DMD). Neuromusc. Disord. 21:569–78 [Google Scholar]
  176. Nelson MD, Rader F, Tang X, Tavyev J, Nelson SF. 176.  et al. 2014. PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology 82:2085–91 [Google Scholar]
  177. Nguyen TM, Ellis JM, Love DR, Davies KE, Gatter KC. 177.  et al. 1991. Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines. J. Cell Biol. 115:1695–700 [Google Scholar]
  178. Ousterout DG, Kabadi AM, Thakore PI, Perez-Pinera P, Brown MT. 178.  et al. 2015. Correction of dystrophin expression in cells from Duchenne muscular dystrophy patients through genomic excision of exon 51 by zinc finger nucleases. Mol. Ther. 23:523–32 [Google Scholar]
  179. Pane M, Mazzone ES, Fanelli L, De Sanctis R, Bianco F. 179.  et al. 2014. Reliability of the Performance of Upper Limb assessment in Duchenne muscular dystrophy. Neuromusc. Disord. 24:201–6 [Google Scholar]
  180. Pane M, Mazzone ES, Sivo S, Sormani MP, Messina S. 180.  et al. 2014. Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes. PLOS ONE 9:e108205 [Google Scholar]
  181. Partridge TA, Morgan JE, Coulton GR, Hoffman EP, Kunkel LM. 181.  1989. Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts. Nature 337:176–79 [Google Scholar]
  182. Pearce M, Blake DJ, Tinsley JM, Byth BC, Campbell L. 182.  et al. 1993. The utrophin and dystrophin genes share similarities in genomic structure. Hum. Mol. Genet. 2:1765–72 [Google Scholar]
  183. Pfizer. 183.  2014. Pfizer initiates phase 2 study of PF-06252616 in Duchenne muscular dystrophy Press Release, Dec. 17. http://www.pfizer.com/news/press-release/press-release-detail/pfizer_initiates_phase_2_study_of_pf_06252616_in_duchenne_muscular_dystrophy
  184. Pons F, Nicholson LV, Robert A, Voit T, Leger JJ. 184.  1993. Dystrophin and dystrophin-related protein (utrophin) distribution in normal and dystrophin-deficient skeletal muscles. Neuromusc. Disord. 3:507–14 [Google Scholar]
  185. Prins KW, Humston JL, Mehta A, Tate V, Ralston E, Ervasti JM. 185.  2009. Dystrophin is a microtubule-associated protein. J. Cell Biol. 186:363–69 [Google Scholar]
  186. Ray PN, Belfall B, Duff C, Logan C, Kean V. 186.  et al. 1985. Cloning of the breakpoint of an X;21 translocation associated with Duchenne muscular dystrophy. Nature 318:672–75 [Google Scholar]
  187. Roberts RG, Coffey AJ, Bobrow M, Bentley DR. 187.  1993. Exon structure of the human dystrophin gene. Genomics 16:536–38 [Google Scholar]
  188. Rodger S, Lochmuller H, Tassoni A, Gramsch K, Konig K. 188.  et al. 2013. The TREAT-NMD care and trial site registry: an online registry to facilitate clinical research for neuromuscular diseases. Orphanet J. Rare Dis. 8:171 [Google Scholar]
  189. Romero NB, Braun S, Benveniste O, Leturcq F, Hogrel JY. 189.  et al. 2004. Phase I study of dystrophin plasmid-based gene therapy in Duchenne/Becker muscular dystrophy. Hum. Gene Ther. 15:1065–76 [Google Scholar]
  190. Rooney JE, Gurpur PB, Burkin DJ. 190.  2009. Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy. PNAS 106:7991–96 [Google Scholar]
  191. Rooney JE, Gurpur PB, Yablonka-Reuveni Z, Burkin DJ. 191.  2009. Laminin-111 restores regenerative capacity in a mouse model for α7 integrin congenital myopathy. Am. J. Pathol. 174:256–64 [Google Scholar]
  192. Rousseau J, Chapdelaine P, Boisvert S, Almeida LP, Corbeil J. 192.  et al. 2011. Endonucleases: tools to correct the dystrophin gene. J. Gene Med. 13:522–37 [Google Scholar]
  193. Rybakova IN, Patel JR, Ervasti JM. 193.  2000. The dystrophin complex forms a mechanically strong link between the sarcolemma and costameric actin. J. Cell Biol. 150:1209–14 [Google Scholar]
  194. Sacco A, Mourkioti F, Tran R, Choi J, Llewellyn M. 194.  et al. 2010. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell 143:1059–71 [Google Scholar]
  195. Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT. 195.  et al. 2000. Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. PNAS 97:13818–23 [Google Scholar]
  196. Sartori R, Gregorevic P, Sandri M. 196.  2014. TGFβ and BMP signaling in skeletal muscle: potential significance for muscle-related disease. Trends Endocrinol. Metab. 25:464–71 [Google Scholar]
  197. Sartori R, Schirwis E, Blaauw B, Bortolanza S, Zhao J. 197.  et al. 2013. BMP signaling controls muscle mass. Nat. Genet. 45:1309–18 [Google Scholar]
  198. Sciorati C, Miglietta D, Buono R, Pisa V, Cattaneo D. 198.  et al. 2011. A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy. Pharmacol. Res. 64:210–17 [Google Scholar]
  199. Sejerson T, Bushby K. 199.  2009. Standards of care for Duchenne muscular dystrophy: brief TREAT-NMD recommendations. Adv. Exp. Med. Biol. 652:13–21 [Google Scholar]
  200. Senter L, Ceoldo S, Petrusa MM, Salviati G. 200.  1995. Phosphorylation of dystrophin: effects on actin binding. Biochem. Biophys. Res. Commun. 206:57–63 [Google Scholar]
  201. Sewry CA, Matsumura K, Campbell KP, Dubowitz V. 201.  1994. Expression of dystrophin-associated glycoproteins and utrophin in carriers of Duchenne muscular dystrophy. Neuromusc. Disord. 4:401–9 [Google Scholar]
  202. Sharp NJ, Kornegay JN, Van Camp SD, Herbstreith MH, Secore SL. 202.  et al. 1992. An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy. Genomics 13:115–21 [Google Scholar]
  203. Shavlakadze T, White J, Hoh JF, Rosenthal N, Grounds MD. 203.  2004. Targeted expression of insulin-like growth factor-I reduces early myofiber necrosis in dystrophic mdx mice. Mol. Ther. 10:829–43 [Google Scholar]
  204. Shemanko CS, Sanghera JS, Milner RE, Pelech S, Michalak M. 204.  1995. Phosphorylation of the carboxyl terminal region of dystrophin by mitogen-activated protein (MAP) kinase. Mol. Cell Biochem. 152:63–70 [Google Scholar]
  205. Shimatsu Y, Katagiri K, Furuta T, Nakura M, Tanioka Y. 205.  et al. 2003. Canine X-linked muscular dystrophy in Japan (CXMDJ). Exp. Anim. 52:93–97 [Google Scholar]
  206. Siriett V, Salerno MS, Berry C, Nicholas G, Bower R. 206.  et al. 2007. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Mol. Ther. 15:1463–70 [Google Scholar]
  207. Skuk D, Goulet M, Roy B, Chapdelaine P, Bouchard JP. 207.  et al. 2006. Dystrophin expression in muscles of Duchenne muscular dystrophy patients after high-density injections of normal myogenic cells. J. Neuropathol. Exp. Neurol. 65:371–86 [Google Scholar]
  208. Skuk D, Roy B, Goulet M, Chapdelaine P, Bouchard JP. 208.  et al. 2004. Dystrophin expression in myofibers of Duchenne muscular dystrophy patients following intramuscular injections of normal myogenic cells. Mol. Ther. 9:475–82 [Google Scholar]
  209. Sonnemann KJ, Heun-Johnson H, Turner AJ, Baltgalvis KA, Lowe DA, Ervasti JM. 209.  2009. Functional substitution by TAT-utrophin in dystrophin-deficient mice. PLOS Med. 6:e1000083 [Google Scholar]
  210. Squire S, Raymackers JM, Vandebrouck C, Potter A, Tinsley J. 210.  et al. 2002. Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system. Hum. Mol. Genet. 11:3333–44 [Google Scholar]
  211. Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA. 211.  et al. 1991. The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature 352:536–39 [Google Scholar]
  212. Straub V, Bittner RE, Leger JJ, Voit T. 212.  1992. Direct visualization of the dystrophin network on skeletal muscle fiber membrane. J. Cell Biol. 119:1183–91 [Google Scholar]
  213. Swiderski K, Shaffer SA, Gallis B, Odom GL, Arnett AL. 213.  et al. 2014. Phosphorylation within the cysteine-rich region of dystrophin enhances its association with β-dystroglycan and identifies a potential novel therapeutic target for skeletal muscle wasting. Hum. Mol. Genet. 23:6697–711 [Google Scholar]
  214. Thies RS, Chen T, Davies MV, Tomkinson KN, Pearson AA. 214.  et al. 2001. GDF-8 propeptide binds to GDF-8 and antagonizes biological activity by inhibiting GDF-8 receptor binding. Growth Factors 18:251–59 [Google Scholar]
  215. Thomas GD, Sander M, Lau KS, Huang PL, Stull JT, Victor RG. 215.  1998. Impaired metabolic modulation of α-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. PNAS 95:15090–95 [Google Scholar]
  216. Tinsley JM, Blake DJ, Roche A, Fairbrother U, Riss J. 216.  et al. 1992. Primary structure of dystrophin-related protein. Nature 360:591–93 [Google Scholar]
  217. Tinsley JM, Deconinck N, Fisher R, Kahn D, Phelps S. 217.  et al. 1998. Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat. Med. 4:1441–44 [Google Scholar]
  218. Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC. 218.  et al. 2011. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLOS ONE 6:e19189 [Google Scholar]
  219. Tinsley JM, Potter AC, Phelps SR, Fisher R, Trickett JI, Davies KE. 219.  1996. Amelioration of the dystrophic phenotype of mdx mice using a truncated utrophin transgene. Nature 384:349–53 [Google Scholar]
  220. Tinsley JM, Robinson N, Davies KE. 220.  2015. Safety, tolerability, and pharmacokinetics of SMT C1100, a 2-arylbenzoxazole utrophin modulator, following single and multiple-dose administration to healthy male adult volunteers. J. Clin. Pharmacol. 55:698–707 [Google Scholar]
  221. Tonlorenzi R, Dellavalle A, Schnapp E, Cossu G, Sampaolesi M. 221.  2007. Isolation and characterization of mesoangioblasts from mouse, dog, and human tissues. Curr. Protoc. Stem Cell Biol. 3:2B.1 [Google Scholar]
  222. Torrente Y, Belicchi M, Marchesi C, D'Antona G, Cogiamanian F. 222.  et al. 2007. Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients. Cell Transplant. 16:563–77 [Google Scholar]
  223. van Deutekom JC, Bremmer-Bout M, Janson AA, Ginjaar IB, Baas F. 223.  et al. 2001. Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Hum. Mol. Genet. 10:1547–54 [Google Scholar]
  224. van Deutekom JC, Janson AA, Ginjaar IB, Frankhuizen WS, Aartsma-Rus A. 224.  et al. 2007. Local dystrophin restoration with antisense oligonucleotide PRO051. N. Engl. J. Med. 357:2677–86 [Google Scholar]
  225. van Ommen GJB, Bertelson C, Ginjaar HB, den Dunnen JT, Bakker E. 225.  et al. 1987. Long-range genomic map of the Duchenne muscular dystrophy (DMD) gene: isolation and use of J66 (DXS268), a distal intragenic marker. Genomics 1:329–36 [Google Scholar]
  226. van Ommen GJB, Verkerk JM, Hofker MH, Monaco AP, Kunkel LM. 226.  et al. 1986. A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X-chromosome. Cell 47:499–504 [Google Scholar]
  227. Verellen-Dumoulin C, Freund M, De Meyer R, Laterre C, Frederic J. 227.  et al. 1984. Expression of an X-linked muscular dystrophy in a female due to translocation involving Xp21 and non-random inactivation of the normal X chromosome. Hum. Genet. 67:115–19 [Google Scholar]
  228. Voisin V, Sebrie C, Matecki S, Yu H, Gillet B. 228.  et al. 2005. l-Arginine improves dystrophic phenotype in mdx mice. Neurobiol. Dis. 20:123–30 [Google Scholar]
  229. Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N. 229.  et al. 2014. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 13:987–96 [Google Scholar]
  230. Vulin A, Barthelemy I, Goyenvalle A, Thibaud JL, Beley C. 230.  et al. 2012. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol. Ther. 20:2120–33 [Google Scholar]
  231. Wagner KR, Fleckenstein JL, Amato AA, Barohn RJ, Bushby K. 231.  et al. 2008. A phase I/II trial of MYO-029 in adult subjects with muscular dystrophy. Ann. Neurol. 63:561–71 [Google Scholar]
  232. Webster C, Silberstein L, Hays AP, Blau HM. 232.  1988. Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy. Cell 52:503–13 [Google Scholar]
  233. Wehling M, Spencer MJ, Tidball JG. 233.  2001. A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. J. Cell Biol. 155:123–31 [Google Scholar]
  234. Weir AP, Burton EA, Harrod G, Davies KE. 234.  2002. A- and B-utrophin have different expression patterns and are differentially up-regulated in mdx muscle. J. Biol. Chem. 277:45285–90 [Google Scholar]
  235. Weir AP, Morgan JE, Davies KE. 235.  2004. A-utrophin up-regulation in mdx skeletal muscle is independent of regeneration. Neuromusc. Disord. 14:19–23 [Google Scholar]
  236. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ. 236.  et al. 2007. PTC124 targets genetic disorders caused by nonsense mutations. Nature 447:87–91 [Google Scholar]
  237. Winand NJ, Edwards M, Pradhan D, Berian CA, Cooper BJ. 237.  1994. Deletion of the dystrophin muscle promoter in feline muscular dystrophy. Neuromusc. Disord. 4:433–45 [Google Scholar]
  238. Wink DA, Mitchell JB. 238.  1998. Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic. Biol. Med. 25:434–56 [Google Scholar]
  239. Worton RG, Duff C, Sylvester JE, Schmickel RD, Willard HF. 239.  1984. Duchenne muscular dystrophy involving translocation of the DMD gene next to ribosomal RNA genes. Science 224:1447–49 [Google Scholar]
  240. Yamamoto H, Hagiwara Y, Mizuno Y, Yoshida M, Ozawa E. 240.  1993. Heterogeneity of dystrophin-associated proteins. J. Biochem. 114:132–39 [Google Scholar]
  241. Yoshida M, Ozawa E. 241.  1990. Glycoprotein complex anchoring dystrophin to sarcolemma. J. Biochem. 108:748–52 [Google Scholar]
  242. Yoshida M, Suzuki A, Yamamoto H, Noguchi S, Mizuno Y, Ozawa E. 242.  1994. Dissociation of the complex of dystrophin and its associated proteins into several unique groups by n-octyl β-d-glucoside. Eur. J. Biochem. 222:1055–61 [Google Scholar]
  243. Zaharieva IT, Calissano M, Scoto M, Preston M, Cirak S. 243.  et al. 2013. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular dystrophy. PLOS ONE 8:e80263 [Google Scholar]
  244. Zanotti S, Negri T, Cappelletti C, Bernasconi P, Canioni E. 244.  et al. 2005. Decorin and biglycan expression is differentially altered in several muscular dystrophies. Brain 128:2546–55 [Google Scholar]
  245. Zatz M, Vianna-Morgante AM, Campos P, Diament AJ. 245.  1981. Translocation (X;6) in a female with Duchenne muscular dystrophy: implications for the localisation of the DMD locus. J. Med. Genet. 18:442–47 [Google Scholar]
  246. Zubrzycka-Gaarn EE, Bulman DE, Karpati G, Burghes AH, Belfall B. 246.  et al. 1988. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature 333:466–69 [Google Scholar]
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The Pathogenesis and Therapy of Muscular Dystrophies
Annual Review of Genomics and Human Genetics 16, 281 (2015); https://doi.org/10.1146/annurev-genom-090314-025003
/content/journals/10.1146/annurev-genom-090314-025003
/content/journals/10.1146/annurev-genom-090314-025003
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