Current understanding of molecular pathology and treatment of cardiomyopathy in duchenne muscular dystrophy

Molecules

Volumn 20, Issue 5, 2015, Pages 8823-8855

  Van Westering, Tirsa L E ^a   Betts, Corinne A ^a   Wood, Matthew J A ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Calcium; Cell Based Therapy; Dystrophin; Exon skipping; Heart; Mitochondria; NNOS; Read Through; Utrophin Up Regulation; Viral Gene Therapy

Indexed keywords

ANIMAL; CARDIOMYOPATHY; DUCHENNE MUSCULAR DYSTROPHY; HUMAN; PATHOLOGY;

ANIMALS; CARDIOMYOPATHIES; HUMANS; MUSCULAR DYSTROPHY, DUCHENNE;

EID: 84964561725     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules20058823     Document Type: Review

References (203)

1. Finsterer, J.; Stöllberger, C. The heart in human dystrophinopathies. Cardiology 2003, 99, 1-19.
2. Mendell, J.R.; Province, M.A.; Moxley, R.T., 3rd; Griggs, R.C.; Brooke, M.H.; Fenichel, G.M.; Miller, J.P.; Kaiser, K.K.; King, W.; Robison, J.; et al. Clinical investigation of Duchenne muscular dystrophy. A methodology for therapeutic trials based on natural history controls. Arch. Neurol. 1987, 44, 808-811.
3. Fayssoil, A.; Nardi, O.; Orlikowski, D.; Annane, D. Cardiomyopathy in Duchenne muscular dystrophy: Pathogenesis and therapeutics. Heart Fail. Rev. 2010, 15, 103-107.
4. Douglas, A.G.L.; Wood, M.J. A splicing therapy for neuromuscular disease. Mol. Cell. Neurosci. 2013, 56, 169-185.
5. Davies, K.E.; Nowak, K.J. Molecular mechanisms of muscular dystrophies: Old and new players. Nat. Rev. Mol. Cell Biol. 2006, 7, 762-773.
6. Mazur, W.; Hor, K.N.; Germann, J.T.; Fleck, R.J.; Al-Khalidi, H.R.; Wansapura, J.P.; Chung, E.S.; Taylor, M.D.; Jefferies, J.L.; Benson, D.W.; et al. Patterns of left ventricular remodeling in patients with Duchenne Muscular Dystrophy: A cardiac MRI study of ventricular geometry, global function, and strain. Int. J. Cardiovasc. Imag. 2012, 28, 99-107.
7. Kirchmann, C.; Kececioglu, D.; Korinthenberg, R.; Dittrich, S. Echocardiographic and electrocardiographic findings of cardiomyopathy in Duchenne and Becker-Kiener muscular dystrophies. Pediatr. Cardiol. 2005, 26, 66-72.
8. Nigro, G.; Comi, L.I.; Politano, L.; Bain, R.J.I. The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Int. J. Cardiol. 1990, 26, 271-277.
9. Bushby, K.; Muntoni, F.; Bourke, J.P. 107th ENMC International Workshop: The management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7-9 June 2002, Naarden, the Netherlands. Neuromuscular Disord. 2003, 13, 166-172.
10. Sultan, A.; Fayaz, M. Prevalence of cardiomyopathy in Duchenne and Becker's muscular dystrophy. J. Ayub Med. Coll. Abbottabad 2008, 20, 7-13.
11. Sanyal, S.K.; Johnson, W.W.; Thapar, M.K.; Pitner, S.E. An ultrastructural basis for electrocardiographic alterations associated with Duchenne's progressive muscular dystrophy. Circulation 1978, 57, 1122-1129.
12. Sanyal, S.K.; Johnson, W.W. Cardiac conduction abnormalities in children with Duchenne's progressive muscular dystrophy: Electrocardiographic features and morphologic correlates. Circulation 1982, 66, 853-863.
13. Perloff, J.K.; Roberts, W.C.; de Leon, A.C., Jr.; O'Doherty, D. The distinctive electrocardiogram of Duchenne's progressive muscular dystrophy. An electrocardiographic-pathologic correlative study. Am. J. Med. 1967, 42, 179-188.
14. Hor, K.N.; Wansapura, J.; Markham, L.W.; Mazur, W.; Cripe, L.H.; Fleck, R.; Benson, D.W.; Gottliebson, W.M. Circumferential Strain Analysis Identifies Strata of Cardiomyopathy in Duchenne Muscular Dystrophy. A Cardiac Magnetic Resonance Tagging Study. J. Am. Coll. Cardiol. 2009, 53, 1204-1210.
15. Hagenbuch, S.C.; Gottliebson, W.M.; Wansapura, J.; Mazur, W.; Fleck, R.; Benson, D.W.; Hor, K.N. Detection of Progressive Cardiac Dysfunction by Serial Evaluation of Circumferential Strain in Patients With Duchenne Muscular Dystrophy. Am. J. Cardiol. 2010, 105, 1451-1455.
16. Hor, K.N.; Taylor, M.D.; Al-Khalidi, H.R.; Cripe, L.H.; Raman, S.V.; Jefferies, J.L.; O'Donnell, R.; Benson, D.W.; Mazur, W. Prevalence and distribution of late gadolinium enhancement in a large population of patients with Duchenne muscular dystrophy: Effect of age and left ventricular systolic function. J. Cardiovasc. Magn. Reson. 2013, 15, 107.
17. Bulfield, G.; Siller, W.G.; Wight, P.A.; Moore, K.J. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc. Natl. Acad. Sci. USA 1984, 81, 1189-1192.
18. Sicinski, P.; Geng, Y.; Ryder-Cook, A.S.; Barnard, E.A.; Darlison, M.G.; Barnard, P.J. The molecular basis of muscular dystrophy in the mdx mouse: A point mutation. Science 1989, 244, 1578-1580.
19. Pastoret, C.; Sebille, A. mdx mice show progressive weakness and muscle deterioration with age. J. Neurol. Sci. 1995, 129, 97-105.
20. Lynch, G.S.; Hinkle, R.T.; Chamberlain, J.S.; Brooks, S.V.; Faulkner, J.A. Force and power output of fast and slow skeletal muscles from mdx mice 6-28 months old. J. Physiol. 2001, 535, 591-600.
21. Stuckey, D.J.; Carr, C.A.; Camelliti, P.; Tyler, D.J.; Davies, K.E.; Clarke, K. In vivo MRI characterization of progressive cardiac dysfunction in the mdx mouse model of muscular dystrophy. PLoS ONE 2012, 7, e28569.
22. Chu, V.; Otero, J.M.; Lopez, O.; Sullivan, M.F.; Morgan, J.P.; Amende, I.; Hampton, T.G. Electrocardiographic findings in mdx mice: A cardiac phenotype of Duchenne muscular dystrophy. Muscle Nerve 2002, 26, 513-519.
23. Wehling-Henricks, M.; Jordan, M.C.; Roos, K.P.; Deng, B.; Tidball, J.G. Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Hum. Mol. Genet. 2005, 14, 1921-1933.
24. Shin, J.; Tajrishi, M.M.; Ogura, Y.; Kumar, A. Wasting mechanisms in muscular dystrophy. Int. J. Biochem. Cell Biol. 2013, 45, 2266-2279.
25. Mosqueira, M.; Baby, S.M.; Lahiri, S.; Khurana, T.S. Ventilatory Chemosensory Drive Is Blunted in the mdx Mouse Model of Duchenne Muscular Dystrophy (DMD). PLoS ONE 2013, 8, e69567.
26. Amann, K.J.; Guo, A.W.X.; Ervasti, J.M. Utrophin lacks the rod domain actin binding activity of dystrophin. J. Biol. Chem. 1999, 274, 35375-35380.
27. Blake, D.J.; Weir, A.; Newey, S.E.; Davies, K.E. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol. Rev. 2002, 82, 291-329.
28. Allen, D.G.; Whitehead, N.P. Duchenne muscular dystrophy-What causes the increased membrane permeability in skeletal muscle? Int. J. Biochem. Cell Biol. 2011, 43, 290-294.
29. Jung, C.; Martins, A.S.; Niggli, E.; Shirokova, N. Dystrophic cardiomyopathy: Amplification of cellular damage by Ca2+ signalling and reactive oxygen species-generating pathways. Cardiovasc. Res. 2008, 77, 766-773.
30. Altamirano, F.; Lopez, J.R.; Henrvquez, C.; Molinski, T.; Allen, P.D.; Jaimovich, E. Increased resting intracellular calcium modulates NF-κB-dependent inducible nitric-oxide synthase gene expression in dystrophic mdx skeletal myotubes. J. Biol. Chem. 2012, 287, 20876-20887.
31. Wehrens, X.H.T.; Lehnart, S.E.; Reiken, S.R.; Marks, A.R. Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor. Circ. Res. 2004, 94, e61-e70.
32. Shirokova, N.; Niggli, E. Cardiac phenotype of Duchenne Muscular Dystrophy: Insights from cellular studies. J. Mol. Cell. Cardiol. 2013, 58, 217-224.
33. Shan, J.; Betzenhauser, M.J.; Kushnir, A.; Reiken, S.; Meli, A.C.; Wronska, A.; Dura, M.; Chen, B.X.; Marks, A.R. Role of chronic ryanodine receptor phosphorylation in heart failure and β-Adrenergic receptor blockade in mice. J. Clin. Investig. 2010, 120, 4375.
34. Lohan, J.; Ohlendieck, K. Drastic reduction in the luminal Ca2+-binding proteins calsequestrin and sarcalumenin in dystrophin-deficient cardiac muscle. BBA-Mol. Basis Dis. 2004, 1689, 252-258.
35. Petrof, B.J.; Shrager, J.B.; Stedman, H.H.; Kelly, A.M.; Sweeney, H.L. Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc. Natl. Acad. Sci. USA 1993, 90, 3710-3714.
36. Yeung, E.W.; Whitehead, N.P.; Suchyna, T.M.; Gottlieb, P.A.; Sachs, F.; Allen, D.G. Effects of stretch-Activated channel blockers on [Ca2+]i and muscle damage in the mdx mouse. J. Physiol. 2005, 562, 367-380.
37. Yasuda, S.; Townsend, D.; Michele, D.E.; Favre, E.G.; Day, S.M.; Metzger, J.M. Dystrophic heart failure blocked by membrane sealant poloxamer. Nature 2005, 436, 1025-1029.
38. Fanchaouy, M.; Polakova, E.; Jung, C.; Ogrodnik, J.; Shirokova, N.; Niggli, E. Pathways of abnormal stress-induced Ca2+ influx into dystrophic mdx cardiomyocytes. Cell Calcium 2009, 46, 114-121.
39. Clarke, M.S.; Khakee, R.; McNeil, P.L. Loss of cytoplasmic basic fibroblast growth factor from physiologically wounded myofibers of normal and dystrophic muscle. J. Cell Sci. 1993, 106, 121-133.
40. De Palma, C.; Clementi, E. Nitric oxide in myogenesis and therapeutic muscle repair. Mol. Neurobiol. 2012, 46, 682-692.
41. Simon, J.N.; Duglan, D.; Casadei, B.; Carnicer, R. Nitric oxide synthase regulation of cardiac excitation-contraction coupling in health and disease. J. Mol. Cell. Cardiol. 2014, 73, 80-91.
42. Zhang, Y.H.; Casadei, B. Sub-cellular targeting of constitutive NOS in health and disease. J. Mol. Cell. Cardiol. 2012, 52, 341-350.
43. Percival, J.M.; Siegel, M.P.; Knowels, G.; Marcinek, D.J. Defects in mitochondrial localization and ATP synthesis in the mdx mouse model of duchenne muscular dystrophy are not alleviated by PDE5 inhibition. Hum. Mol. Genet. 2013, 22, 153-167.
44. Viola, H.M.; Arthur, P.G.; Hool, L.C. Evidence for regulation of mitochondrial function by the L-Type Ca2+ channel in ventricular myocytes. J. Mol. Cell. Cardiol. 2009, 46, 1016-1026.
45. Viola, H.M.; Adams, A.M.; Davies, S.M.K.; Fletcher, S.; Filipovska, A.; Hool, L.C. Impaired functional communication between the L-Type calcium channel and mitochondria contributes to metabolic inhibition in the mdx heart. Proc. Natl. Acad. Sci. USA 2014, E2905-E2914.
46. Li, Y.; Zhang, S.; Zhang, X.; Li, J.; Ai, X.; Zhang, L.; Yu, D.; Ge, S.; Peng, Y.; Chen, X. Blunted cardiac beta-Adrenergic response as an early indication of cardiac dysfunction in Duchenne muscular dystrophy. Cardiovasc. Res. 2014, 103, 60-71.
47. Rohman, M.S.; Emoto, N.; Takeshima, Y.; Yokoyama, M.; Matsuo, M. Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts. Biochem. Biophys. Res. Commun. 2003, 310, 228-235.
48. Respress, J.L.; van Oort, R.J.; Li, N.; Rolim, N.; Dixit, S.; DeAlmeida, A.; Voigt, N.; Lawrence, W.S.; Skapura, D.G.; Skardal, K.; et al. Role of RyR2 Phosphorylation at S2814 during Heart Failure Progression. Circ. Res. 2012, 110, 1474-1483.
49. Damy, T.; Ratajczak, P.; Shah, A.M.; Camors, E.; Marty, I.; Hasenfuss, G.; Marotte, F.; Samuel, J.L.; Heymes, C. Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet 2004, 363, 1365-1367.
50. Chang, W.J.; Iannaccone, S.T.; Lau, K.S.; Masters, B.S.; McCabe, T.J.; McMillan, K.; Padre, R.C.; Spencer, M.J.; Tidball, J.G.; Stull, J.T. Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proc. Natl. Acad. Sci. USA 1996, 93, 9142-9147.
51. Wallace, G.Q.; McNally, E.M. Mechanisms of muscle degeneration, regeneration, and repair in the muscular dystrophies. Annu. Rev. Physiol. 2009, 71, 37-57.
52. Lorin, C.; Vogeli, I.; Niggli, E. Dystrophic cardiomyopathy: Role of TRPV2 channels in stretch-induced cell damage. Cardiovasc. Res. 2015, 106, 153-162.
53. Ward, M.L.; Williams, I.A.; Chu, Y.; Cooper, P.J.; Ju, Y.K.; Allen, D.G. Stretch-Activated channels in the heart: Contributions to length-dependence and to cardiomyopathy. Prog. Biophys. Mol. Biol. 2008, 97, 232-249.
54. Harisseh, R.; Chatelier, A.; Magaud, C.; Diliot, N.; Constantin, B. Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of α1-syntrophin and PLC/PKC in SOCE regulation. Am. J. Physiol. Cell Physiol. 2013, 304, C881-C894.
55. Blaustein, M.P.; Lederer, W.J. Sodium/calcium exchange: Its physiological implications. Physiol. Rev. 1999, 79, 763-854.
56. Burr, A.R.; Millay, D.P.; Goonasekera, S.A; Park, K.H.; Sargent, M.A; Collins, J.; Altamirano, F.; Philipson, K.D.; Allen, P.D.; Ma, J.; et al. Na+ dysregulation coupled with Ca2+ entry through NCX1 promotes muscular dystrophy in mice. Mol. Cell. Biol. 2014, 34, 1991-2002.
57. Gavillet, B.; Rougier, J.S.; Domenighetti, A.A.; Behar, R.; Boixel, C.; Ruchat, P.; Lehr, H.A.; Pedrazzini, T.; Abriel, H. Cardiac sodium channel Nav1.5 is regulated by a multiprotein complex composed of syntrophins and dystrophin. Circ. Res. 2006, 99, 407-414.
58. Dyachenko, V.; Husse, B.; Rueckschloss, U.; Isenberg, G. Mechanical deformation of ventricular myocytes modulates both TRPC6 and Kir2.3 channels. Cell Calcium 2009, 45, 38-54.
59. Seo, K.; Rainer, P.P.; Lee, D.I.; Hao, S.; Bedja, D.; Birnbaumer, L.; Cingolani, O.H.; Kass, D.A. Hyperactive adverse mechanical stress responses in dystrophic heart are coupled to transient receptor potential canonical 6 and blocked by cgmp-protein kinase g modulation. Circ. Res. 2014, 114, 823-832.
60. Millay, D.P.; Goonasekera, S.A.; Sargent, M.A.; Maillet, M.; Aronow, B.J.; Molkentin, J.D. Calcium influx is sufficient to induce muscular dystrophy through a TRPC-dependent mechanism. Proc. Natl. Acad. Sci. USA 2009, 106, 19023-19028.
61. Hohaus, A.; Person, V.; Behlke, J.; Schaper, J.; Morano, I.; Haase, H. The carboxyl-Terminal region of ahnak provides a link between cardiac L-Type Ca2+ channels and the actin-based cytoskeleton. FASEB J. 2002, 16, 1205-1216.
62. Sadeghi, A.; Doyle, A.D.; Johnson, B.D. Regulation of the cardiac L-Type Ca2+ channel by the actin-binding proteins alpha-Actinin and dystrophin. Am. J. Physiol. Cell Physiol. 2002, 282, C1502-C1511.
63. Tanabe, T.; Beam, K.G.; Adams, B.A.; Niidome, T.; Numa, S. Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling. Nature 1990, 346, 567-569.
64. Koenig, X.; Rubi, L.; Obermair, G.J.; Cervenka, R.; Dang, X.B.; Lukacs, P.; Kummer, S.; Bittner, R.E.; Kubista, H.; Todt, H.; Hilber, K. Enhanced currents through L-Type calcium channels in cardiomyocytes disturb the electrophysiology of the dystrophic heart. Am. J. Physiol. Heart Circ. Physiol. 2013, 306, H564-H573.
65. Alberts, B.; Johnson, A.; Lewis, J.; Raff, M.; Roberts, K.; Walter, P. Molecular Biology of the Cell, 5th ed.; Garland Science: New York, NY, USA, 2007.
66. Niggli, E.; Ullrich, N.D.; Gutierrez, D.; Kyrychenko, S.; Poláková, E.; Shirokova, N. Posttranslational modifications of cardiac ryanodine receptors: Ca2+ signaling and EC-coupling. BBA-Mol. Cell Res. 2013, 1833, 866-875.
67. Marx, S.O.; Reiken, S.; Hisamatsu, Y.; Jayaraman, T.; Burkhoff, D.; Rosemblit, N.; Marks, A.R. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): Defective regulation in failing hearts. Cell 2000, 101, 365-376.
68. Kyrychenko, S.; Poláková, E.; Kang, C.; Pocsai, K.; Ullrich, N.D.; Niggli, E.; Shirokova, N. Hierarchical accumulation of RyR post-Translational modifications drives disease progression in dystrophic cardiomyopathy. Cardiovasc. Res. 2013, 97, 666-675.
69. Mijares, A.; Altamirano, F.; Kolster, J.; Adams, J.A.; López, J.R. Biochemical and Biophysical Research Communications Age-dependent changes in diastolic Ca2+ and Na+ concentrations in dystrophic cardiomyopathy: Role of Ca2+ entry and IP 3. Biochem. Biophys. Res. Commun. 2014, 452, 1054-1059.
70. Gervásio, O.L.; Whitehead, N.P.; Yeung, E.W.; Phillips, W.D.; Allen, D.G. TRPC1 binds to caveolin-3 and is regulated by Src kinase-role in Duchenne muscular dystrophy. J. Cell Sci. 2008, 121, 2246-2255.
71. Ashley, E.A.; Sears, C.E.; Bryant, S.M.; Watkins, H.C.; Casadei, B. Cardiac nitric oxide synthase 1 regulates basal and beta-Adrenergic contractility in murine ventricular myocytes. Circulation 2002, 105, 3011-3016.
72. Wang, H.; Kohr, M.J.; Traynham, C.J.; Wheeler, D.G.; Janssen, P.M.L.; Ziolo, M.T. Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban. Am. J. Physiol. Cell Physiol. 2008, 294, C1566-C1575.
73. Nisoli, E.; Falcone, S.; Tonello, C.; Cozzi, V.; Palomba, L.; Fiorani, M.; Pisconti, A.; Brunelli, S.; Cardile, A.; Francolini, M.; et al. Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc. Natl. Acad. Sci. USA 2004, 101, 16507-16512.
74. Lai, Y.; Zhao, J.; Yue, Y.; Wasala, N.B.; Duan, D. Partial restoration of cardiac function with δPDZ nNOS in aged mdx model of Duchenne cardiomyopathy. Hum. Mol. Genet. 2014, 23, 3189-3199.
75. Alonso, M.T.; Villalobos, C.; Chamero, P.; Alvarez, J.; García-Sancho, J. Calcium microdomains in mitochondria and nucleus. Cell Calcium 2006, 40, 513-525.
76. Ichas, F.; Jouaville, L.S.; Mazat, J.P. Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals. Cell 1997, 89, 1145-1153.
77. Zorov, D.B.; Juhaszova, M.; Sollott, S.J. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release. Physiol. Rev. 2014, 94, 909-950.
78. Khairallah, M.; Khairallah, R.; Young, M.E.; Dyck, J.R.B.; Petrof, B.J.; Des Rosiers, C. Metabolic and signaling alterations in dystrophin-deficient hearts precede overt cardiomyopathy. J. Mol. Cell. Cardiol. 2007, 43, 119-129.
79. Khairallah, R.J.; Khairallah, M.; Gélinas, R.; Bouchard, B.; Young, M.E.; Allen, B.G.; Lopaschuk, G.D.; Deschepper, C.F.; Des Rosiers, C. Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation. J. Mol. Cell. Cardiol. 2008, 45, 230-239.
80. Bernardi, P.; di Lisa, F. The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection. J. Mol. Cell. Cardiol. 2015, 78, 100-106.
81. Pan, X.; Liu, J.; Nguyen, T.; Liu, C.; Sun, J.; Teng, Y.; Fergusson, M.M.; Rovira, I.I.; Allen, M.; Springer, D.A; et al. The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. Nat. Cell Biol. 2013, 15, 1464-1472.
82. Millay, D.P.; Sargent, M.A.; Osinska, H.; Baines, C.P.; Barton, E.R.; Vuagniaux, G.; Sweeney, H.L.; Robbins, J.; Molkentin, J.D. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat. Med. 2008, 14, 442-447.
83. Griggs, R.C.; Moxley, R.T.; Mendell, J.R.; Fenichel, G.M.; Brooke, M.H.; Pestronk, A.; Miller, J.P. Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. Arch. Neurol. 1991, 48, 383-388.
84. Biggar, W.D.; Harris, V.A.; Eliasoph, L.; Alman, B. Long-Term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul. Disord. 2006, 16, 249-255.
85. Barber, B.J.; Andrews, J.G.; Lu, Z.; West, N.A.; Meaney, F.J.; Price, E.T.; Gray, A.; Sheehan, D.W.; Pandya, S.; Yang, M.; et al. Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy. J. Pediatr. 2013, 163, 1080-1084.
86. Wagner, K.R.; Lechtzin, N.; Judge, D.P. Current treatment of adult Duchenne muscular dystrophy. Biochim. Biophys. Acta 2007, 1772, 229-237.
87. Melacini, P.; Vianello, A.; Villanova, C.; Fanin, M.; Miorin, M.; Angelini, C.; Dalla Volta, S. Cardiac and respiratory involvement in advanced stage Duchenne muscular dystrophy. Neuromuscul. Disord. 1996, 6, 367-376.
88. Finsterer, J. Cardiopulmonary support in Duchenne muscular dystrophy. Lung 2006, 184, 205-215.
89. Toussaint, M.; Chatwin, M.; Soudon, P. Mechanical ventilation in Duchenne patients with chronic respiratory insufficiency: Clinical implications of 20 years published experience. Chron. Respir. Dis. 2007, 4, 167-177.
90. Goemans, N.; Buyse, G. Current treatment and management of dystrophinopathies. Curr. Treat. Options Neurol. 2014, 16, 1-13.
91. Viollet, L.; Thrush, P.T.; Flanigan, K.M.; Mendell, J.R.; Allen, H.D. Effects of angiotensin-converting enzyme inhibitors and/or beta blockers on the cardiomyopathy in duchenne muscular dystrophy. Am. J. Cardiol. 2012, 110, 98-102.
92. Ogata, H.; Ishikawa, Y.; Minami, R. Beneficial effects of beta-blockers and angiotensin-converting enzyme inhibitors in Duchenne muscular dystrophy. [Erratum appears in J Cardiol. 2009 Apr;53(2):316]. J. Cardiol. 2009, 53, 72-78.
93. Blain, A.; Greally, E.; Laval, S.; Blamire, A.; Straub, V.; MacGowan, G.A. Beta-Blockers, Left and Right Ventricular Function, and in-Vivo Calcium Influx in Muscular Dystrophy Cardiomyopathy. PLoS ONE 2013, 8, e57260.
94. Fayssoil, A.; Nardi, O.; Annane, D.; Orlikowski, D. Successful cardiac resynchronisation therapy in Duchenne muscular dystrophy: A 5-year follow-up. Presse Med. 2014, 43, 330-331.
95. Ryan, T.D.; Jefferies, J.L.; Sawnani, H.; Wong, B.L.; Gardner, A.; Del Corral, M.; Lorts, A.; Morales, D.L.S. Implantation of the HeartMate II and HeartWare left ventricular assist devices in patients with duchenne muscular dystrophy: Lessons learned from the first applications. ASAIO J. 2014, 60, 246-248.
96. Spurney, C.F.; Guerron, A.D.; Yu, Q.; Sali, A.; van der Meulen, J.H.; Hoffman, E.P.; Nagaraju, K. Membrane sealant Poloxamer P188 protects against isoproterenol induced cardiomyopathy in dystrophin deficient mice. BMC Cardiovasc. Disord. 2011, 11, 20.
97. Khairallah, M.; Khairallah, R.J.; Young, M.E.; Allen, B.G.; Gillis, M.A.; Danialou, G.; Deschepper, C.F.; Petrof, B.J.; Des Rosiers, C. Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. Proc. Natl. Acad. Sci. USA 2008, 105, 7028-7033.
98. Adamo, C.M.; Dai, D.-F.; Percival, J.M.; Minami, E.; Willis, M.S.; Patrucco, E.; Froehner, S.C.; Beavo, J.A. Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. USA 2010, 107, 19079-19083.
99. Percival, J.M.; Whitehead, N.P.; Adams, M.E.; Adamo, C.M.; Beavo, J.A.; Froehner, S.C. Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy. J. Pathol. 2012, 228, 77-87.
100. Leung, D.G.; Herzka, D.A.; Thompson, W.R.; He, B.; Bibat, G.; Tennekoon, G.; Russell, S.D.; Schuleri, K.H.; Lardo, A.C.; Kass, D.A.; et al. Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy. Ann. Neurol. 2014, 76, 541-549.
101. Witting, N.; Kruuse, C.; Nyhuus, B.; Prahm, K.; Citirak, G.; Lundgaard, S.; von Huth, S.; Vejlstrup, N.; Lindberg, U.; Krag, T.; Vissing, J. Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy. Ann. Neurol. 2014, 76, 550-557.
102. Spurney, C.F.; Sali, A.; Guerron, A.D.; Iantorno, M.; Yu, Q.; Gordish-Dressman, H.; Rayavarapu, S.; van der Meulen, J.; Hoffman, E.P.; Nagaraju, K. Losartan decreases cardiac muscle fibrosis and improves cardiac function in dystrophin-deficient mdx mice. J. Cardiovasc. Pharmacol. Ther. 2011, 16, 87-95.
103. Van Erp, C.; Irwin, N.G.; Hoey, A.J. Long-Term administration of pirfenidone improves cardiac function in mdx mice. Muscle Nerve 2006, 34, 327-334.
104. Vianello, S.; Consolaro, F.; Bich, C.; Cancela, J.M.; Roulot, M.; Lanchec, E.; Touboul, D.; Brunelle, A.; Israël, M.; Benoit, E.; et al. Low doses of arginine butyrate derivatives improve dystrophic phenotype and restore membrane integrity in DMD models. FASEB J. 2014, 28, 2603-2619.
105. Sciorati, C.; Staszewsky, L.; Zambelli, V.; Russo, I.; Salio, M.; Novelli, D.; Di Grigoli, G.; Moresco, R.M.; Clementi, E.; Latini, R. Ibuprofen plus isosorbide dinitrate treatment in the mdx mice ameliorates dystrophic heart structure. Pharmacol. Res. 2013, 73, 35-43.
106. Cossu, M.V.; Cattaneo, D.; Fucile, S.; Pellegrino, P.; Baldelli, S.; Cozzi, V.; Capetti, A.; Clementi, E. Combined isosorbide dinitrate and ibuprofen as a novel therapy for muscular dystrophies: Evidence from Phase I studies in healthy volunteers. Drug Des. Devel. Ther. 2014, 8, 411-419.
107. Tinsley, J.M.; Potter, A.C.; Phelps, S.R.; Fisher, R.; Trickett, J.I.; Davies, K.E. Amelioration of the dystrophic phenotype of mdx mice using a truncated utrophin transgene. Nature 1996, 384, 349-353.
108. Tinsley, J.; Deconinck, N.; Fisher, R.; Kahn, D.; Phelps, S.; Gillis, J.M.; Davies, K. Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat. Med. 1998, 4, 1441-1444.
109. Gilbert, R.; Nalbanoglu, J.; Tinsley, J.M.; Massie, B.; Davies, K.E.; Karpati, G. Efficient utrophin expression following adenovirus gene transfer in dystrophic muscle. Biochem. Biophys. Res. Commun. 1998, 242, 244-247.
110. Corbi, N.; Libri, V.; Fanciulli, M.; Tinsley, J.M.; Davies, K.E.; Passananti, C. The artificial zinc finger coding gene "Jazz" binds the utrophin promoter and activates transcription. Gene Ther. 2000, 7, 1076-1083.
111. Lu, Y.; Tian, C.; Danialou, G.; Gilbert, R.; Petrof, B.J.; Karpati, G.; Nalbantoglu, J. Targeting artificial transcription factors to the utrophin A promoter: Effects on dystrophic pathology and muscle function. J. Biol. Chem. 2008, 283, 34720-34727.
112. Onori, A.; Pisani, C.; Strimpakos, G.; Monaco, L.; Mattei, E.; Passananti, C.; Corbi, N. UtroUp is a novel six zinc finger artificial transcription factor that recognises 18 base pairs of the utrophin promoter and efficiently drives utrophin upregulation. BMC Mol. Biol. 2013, 14, 3.
113. Amenta, A.R.; Yilmaz, A.; Bogdanovich, S.; McKechnie, B.A; Abedi, M.; Khurana, T.S.; Fallon, J.R. Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in mdx mice. Proc. Natl. Acad. Sci. USA 2011, 108, 762-767.
114. Tinsley, J.M.; Fairclough, R.J.; Storer, R.; Wilkes, F.J.; Potter, A.C.; Squire, S.E.; Powell, D.S.; Cozzoli, A.; Capogrosso, R.F.; Lambert, A.; et al. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS ONE 2011, 6, e19189.
115. Tinsley, J.; Robinson, N.; Davies, K.E. Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, Following Single-And Multiple-Dose Administration to Healthy Male Adult Volunteers Jon Tinsley, PhD. J. Clin. Pharmacol. 2015, 55, 698-707.
116. Barton-Davis, E.R.; Cordier, L.; Shoturma, D.I.; Leland, S.E.; Sweeney, H.L. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J. Clin. Investig. 1999, 104, 375-381.
117. Malik, V.; Rodino-Klapac, L.R.; Viollet, L.; Wall, C.; King, W.; Al-Dahhak, R.; Lewis, S.; Shilling, C.J.; Kota, J.; Serrano-Munuera, C.; et al. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann. Neurol. 2010, 67, 771-780.
118. Arakawa, M.; Shiozuka, M.; Nakayama, Y.; Hara, T.; Hamada, M.; Kondo, S.; Ikeda, D.; Takahashi, Y.; Sawa, R.; Nonomura, Y.; et al. Negamycin Restores Dystrophin Expression in Skeletal and Cardiac Muscles of mdx Mice. J. Biochem. 2003, 134, 751-758.
119. Welch, E.M.; Barton, E.R.; Zhuo, J.; Tomizawa, Y.; Friesen, W.J.; Trifillis, P.; Paushkin, S.; Patel, M.; Trotta, C.R.; Hwang, S.; et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 2007, 447, 87-91.
120. Hirawat, S.; Welch, E.M.; Elfring, G.L.; Northcutt, V.J.; Paushkin, S.; Hwang, S.; Leonard, E.M.; Almstead, N.G.; Ju, W.; Peltz, S.W.; et al. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single-And multiple-dose administration to healthy male and female adult volunteers. J. Clin. Pharmacol. 2007, 47, 430-444.
121. Finkel, R.S.; Flanigan, K.M.; Wong, B.; Bönnemann, C.; Sampson, J.; Sweeney, H.L.; Reha, A.; Northcutt, V.J.; Elfring, G.; Barth, J.; et al. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLoS ONE 2013, 8, e81302.
122. Bushby, K.; Finkel, R.; Wong, B.; Barohn, R.; Campbell, C.; Comi, G.P.; Connolly, M.; Day, J.W.; Flanigan, K.M. Ataluren Treatment of Patients with Nonsense Mutation Dystrophinopathy. Muscle Nerve 2014, 50, 477-487.
123. Kayali, R.; Ku, J.M.; Khitrov, G.; Jung, M.E.; Prikhodko, O.; Bertoni, C. Read-Through compound 13 restores dystrophin expression and improves muscle function in the MDX mouse model for duchenne muscular dystrophy. Hum. Mol. Genet. 2012, 21, 4007-4020.
124. Li, S.; Kimura, E.; Fall, B.M.; Reyes, M.; Angello, J.C.; Welikson, R.; Hauschka, S.D.; Chamberlain, J.S. Stable transduction of myogenic cells with lentiviral vectors expressing a minidystrophin. Gene Ther. 2005, 12, 1099-1108.
125. Wang, X.; Ha, T.; Liu, L.; Zou, J.; Zhang, X.; Kalbfleisch, J.; Gao, X.; Williams, D.; Li, C. Increased expression of microRNA-146a decreases myocardial ischaemia/reperfusion injury. Cardiovasc. Res. 2013, 97, 432-442.
126. Kimura, E.; Li, S.; Gregorevic, P.; Fall, B.M.; Chamberlain, J.S. Dystrophin delivery to muscles of mdx mice using lentiviral vectors leads to myogenic progenitor targeting and stable gene expression. Mol. Ther. 2010, 18, 206-213.
127. DelloRusso, C.; Scott, J.M.; Hartigan-O'Connor, D.; Salvatori, G.; Barjot, C.; Robinson, A.S.; Crawford, R.W.; Brooks, S.V.; Chamberlain, J.S. Functional correction of adult mdx mouse muscle using gutted adenoviral vectors expressing full-length dystrophin. Proc. Natl. Acad. Sci. USA 2002, 99, 12979-12984.
128. Foster, H.; Sharp, P.S.; Athanasopoulos, T.; Trollet, C.; Graham, I.R.; Foster, K.; Wells, D.J.; Dickson, G. Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2/8 gene transfer. Mol. Ther. 2008, 16, 1825-1832.
129. Gregorevic, P.; Allen, J.M.; Minami, E.; Blankinship, M.J.; Haraguchi, M.; Meuse, L.; Finn, E.; Adams, M.E.; Froehner, S.C.; Murry, C.E.; et al. rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice. Nat. Med. 2006, 12, 787-789.
130. Gregorevic, P.; Blankinship, M.J.; Allen, J.M.; Chamberlain, J.S. Systemic microdystrophin gene delivery improves skeletal muscle structure and function in old dystrophic mdx mice. Mol. Ther. 2008, 16, 657-664.
131. Kornegay, J.N.; Li, J.; Bogan, J.R.; Bogan, D.J.; Chen, C.; Zheng, H.; Wang, B.; Qiao, C.; Howard, J.F.; Xiao, X. Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs. Mol. Ther. 2010, 18, 1501-1508.
132. Bostick, B.; Yue, Y.; Lai, Y.; Long, C.; Li, D.; Duan, D. Adeno-Associated virus serotype-9 microdystrophin gene therapy ameliorates electrocardiographic abnormalities in mdx mice. Hum. Gene Ther. 2008, 19, 851-856.
133. Schinkel, S.; Bauer, R.; Bekeredjian, R.; Stucka, R.; Rutschow, D.; Lochmöller, H.; Kleinschmidt, J.A.; Katus, H.A.; Möller, O.J. Long-Term Preservation of Cardiac Structure and Function After Adeno-Associated Virus Serotype 9-Mediated Microdystrophin Gene Transfer in mdx Mice. Hum. Gene Ther. 2012, 23, 566-575.
134. Partridge, T.A.; Morgan, J.E.; Coulton, G.R.; Hoffman, E.P.; Kunkel, L.M. Conversion of mdx myofibres from dystrophin-negative to-positive by injection of normal myoblasts. Nature 1989, 337, 176-179.
135. Mendell, J.R.; Kissel, J.T.; Amato, A.A.; King, W.; Signore, L.; Prior, T.W.; Sahenk, Z.; Benson, S.; McAndrew, P.E.; Rice, R. Myoblast transfer in the treatment of Duchenne's muscular dystrophy. N. Engl. J. Med. 1995, 333, 832-838.
136. Muir, L.A.; Nguyen, Q.G.; Hauschka, S.D.; Chamberlain, J.S. Engraftment potential of dermal fibroblasts following in vivo myogenic conversion in immunocompetent dystrophic skeletal muscle. Mol. Ther. Methods Clin. Dev. 2014, 1, 14025.
137. Gussoni, E.; Soneoka, Y.; Strickland, C.D.; Buzney, E.A; Khan, M.K.; Flint, A.F.; Kunkel, L.M.; Mulligan, R.C. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999, 401, 390-394.
138. Dell'Agnola, C.; Wang, Z.; Storb, R.; Tapscott, S.J.; Kuhr, C.S.; Hauschka, S.D.; Lee, R.S.; Sale, G.E.; Zellmer, E.; Gisburne, S.; et al. Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs. Blood 2004, 104, 4311-4318.
139. Benchaouir, R.; Meregalli, M.; Farini, A.; D'Antona, G.; Belicchi, M.; Goyenvalle, A.; Battistelli, M.; Bresolin, N.; Bottinelli, R.; Garcia, L.; et al. Restoration of Human Dystrophin Following Transplantation of Exon-Skipping-Engineered DMD Patient Stem Cells into Dystrophic Mice. Cell Stem Cell 2007, 1, 646-657.
140. Torrente, Y.; Belicchi, M.; Marchesi, C.; D'Antona, G.; Cogiamanian, F.; Pisati, F.; Gavina, M.; Giordano, R.; Tonlorenzi, R.; Fagiolari, G.; et al. Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients. Cell Transplant. 2007, 16, 563-577.
141. Sampaolesi, M.; Blot, S.; D'Antona, G.; Granger, N.; Tonlorenzi, R.; Innocenzi, A.; Mognol, P.; Thibaud, J.-L.; Galvez, B.G.; Barthélémy, I.; et al. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 2006, 444, 574-579.
142. Goudenege, S.; Lamarre, Y.; Dumont, N.; Rousseau, J.; Frenette, J.; Skuk, D.; Tremblay, J.P. Laminin-111: A potential therapeutic agent for Duchenne muscular dystrophy. Mol. Ther. 2010, 18, 2155-2163.
143. Goudenege, S.; Lebel, C.; Huot, N.B.; Dufour, C.; Fujii, I.; Gekas, J.; Rousseau, J.; Tremblay, J.P. Myoblasts Derived From Normal hESCs and Dystrophic hiPSCs Efficiently Fuse with Existing Muscle Fibers Following Transplantation. Mol. Ther. 2012, 20, 2153-2167.
144. Darabi, R.; Arpke, R.W.; Irion, S.; Dimos, J.T.; Grskovic, M.; Kyba, M.; Perlingeiro, R.C.R. Human ES-And iPS-derived myogenic progenitors restore dystrophin and improve contractility upon transplantation in dystrophic mice. 2012, 10, 610-619.
145. Lu, Q.L.; Mann, C.J.; Lou, F.; Bou-Gharios, G.; Morris, G.E.; Xue, S.; Fletcher, S.; Partridge, T.A.; Wilton, S.D. Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat. Med. 2003, 9, 1009-1014.
146. Lu, Q.L.; Rabinowitz, A.; Chen, Y.C.; Yokota, T.; Yin, H.; Alter, J.; Jadoon, A.; Bou-Gharios, G.; Partridge, T. Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc. Natl. Acad. Sci. USA 2005, 102, 198-203.
147. Flanigan, K.M.; Voit, T.; Rosales, X.Q.; Servais, L.; Kraus, J.E.; Wardell, C.; Morgan, A.; Dorricott, S.; Nakielny, J.; Quarcoo, N.; et al. Pharmacokinetics and safety of single doses of drisapersen in non-Ambulant subjects with Duchenne muscular dystrophy: results of a double-blind randomized clinical trial. Neuromuscul. Disord. 2014, 24, 16-24.
148. Goemans, N.M.; Tulinius, M.; van den Akker, J.T.; Burm, B.E.; Ekhart, P.F.; Heuvelmans, N.; Holling, T.; Janson, A.A.; Platenburg, G.J.; Sipkens, J.A.; et al. Systemic Administration of PRO051 in Duchenne's Muscular Dystrophy. N. Engl. J. Med. 2011, 364, 1513-1522.
149. lter, J.; Lou, F.; Rabinowitz, A.; Yin, H.; Rosenfeld, J.; Wilton, S.D.; Partridge, T.A.; Lu, Q.L. Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nat. Med. 2006, 12, 175-177.
150. Wu, B.; Xiao, B.; Cloer, C.; Shaban, M.; Sali, A.; Lu, P.; Li, J.; Nagaraju, K.; Xiao, X.; Lu, Q.L. One-year treatment of morpholino antisense oligomer improves skeletal and cardiac muscle functions in dystrophic mdx mice. Mol. Ther. 2011, 19, 576-583.
151. Kinali, M.; Arechavala-Gomeza, V.; Feng, L.; Cirak, S.; Hunt, D.; Adkin, C.; Guglieri, M.; Ashton, E.; Abbs, S.; Nihoyannopoulos, P.; et al. 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. 2009, 8, 918-928.
152. Cirak, S.; Arechavala-Gomeza, V.; Guglieri, M.; Feng, L.; Torelli, S.; Anthony, K.; Abbs, S.; Garralda, M.E.; Bourke, J.; Wells, D.J.; et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: An open-label, phase 2, dose-escalation study. Lancet 2011, 378, 595-605.
153. Mendell, J.R.; Rodino-Klapac, L.R.; Sahenk, Z.; Roush, K.; Bird, L.; Lowes, L.P.; Alfano, L.; Gomez, A.M.; Lewis, S.; Kota, J.; et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann. Neurol. 2013, 74, 637-647.
154. Goyenvalle, A.; Griffith, G.; Babbs, A.; El Andaloussi, S.; Ezzat, K.; Avril, A.; Dugovic, B.; Chaussenot, R.; Ferry, A.; Voit, T.; et al. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat. Med. 2015, 21, 270-275.
155. Wu, B.; Li, Y.; Morcos, P.A.; Doran, T.J.; Lu, P.; Lu, Q.L. Octa-guanidine morpholino restores dystrophin expression in cardiac and skeletal muscles and ameliorates pathology in dystrophic mdx mice. Mol. Ther. 2009, 17, 864-871.
156. Yokota, T.; Nakamura, A.; Nagata, T.; Saito, T.; Kobayashi, M.; Aoki, Y.; Echigoya, Y.; Partridge, T.; Hoffman, E.P.; Takeda, S. Extensive and prolonged restoration of dystrophin expression with vivo-morpholino-mediated multiple exon skipping in dystrophic dogs. Nucleic Acid Ther. 2012, 22, 306-315.
157. Jearawiriyapaisarn, N.; Moulton, H.M.; Buckley, B.; Roberts, J.; Sazani, P.; Fucharoen, S.; Iversen, P.L.; Kole, R. Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice. Mol. Ther. 2008, 16, 1624-1629.
158. Wu, B.; Moulton, H.M.; Iversen, P.L.; Jiang, J.; Li, J.; Li, J.; Spurney, C.F.; Sali, A.; Guerron, A.D.; Nagaraju, K.; et al. Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc. Natl. Acad. Sci. USA 2008, 105, 14814-14819.
159. Moulton, H.M.; Fletcher, S.; Neuman, B.W.; McClorey, G.; Stein, D.A.; Abes, S.; Wilton, S.D.; Buchmeier, M.J.; Lebleu, B.; Iversen, P.L. Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo. Biochem. Soc. Trans. 2007, 35, 826-828.
160. Fletcher, S.; Honeyman, K.; Fall, A.M.; Harding, P.L.; Johnsen, R.D.; Steinhaus, J.P.; Moulton, H.M.; Iversen, P.L.; Wilton, S.D. Morpholino oligomer-mediated exon skipping averts the onset of dystrophic pathology in the mdx mouse. Mol. Ther. 2007, 15, 1587-1592.
161. Goyenvalle, A.; Babbs, A.; Powell, D.; Kole, R.; Fletcher, S.; Wilton, S.D.; Davies, K.E. Prevention of dystrophic pathology in severely affected dystrophin/utrophin-deficient mice by morpholino-oligomer-mediated exon-skipping. Mol. Ther. 2010, 18, 198-205.
162. Deconinck, A.E.; Rafael, J.A.; Skinner, J.A.; Brown, S.C.; Potter, A.C.; Metzinger, L.; Watt, D.J.; Dickson, J.G.; Tinsley, J.M.; Davies, K.E. Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. Cell 1997, 90, 717-727.
163. Yin, H.; Moulton, H.M.; Seow, Y.; Boyd, C.; Boutilier, J.; Iverson, P.; Wood, M.J.A. Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. Hum. Mol. Genet. 2008, 17, 3909-3918.
164. Wu, R.P.; Youngblood, D.S.; Hassinger, J.N.; Lovejoy, C.E.; Nelson, M.H.; Iversen, P.L.; Moulton, H.M. Cell-penetrating peptides as transporters for morpholino oligomers: Effects of amino acid composition on intracellular delivery and cytotoxicity. Nucleic Acids Res. 2007, 35, 5182-5191.
165. Yin, H.; Saleh, A.F.; Betts, C.; Camelliti, P.; Seow, Y.; Ashraf, S.; Arzumanov, A.; Hammond, S.; Merritt, T.; Gait, M.J.; et al. Pip5 transduction peptides direct high efficiency oligonucleotide-mediated dystrophin exon skipping in heart and phenotypic correction in mdx mice. Mol. Ther. 2011, 19, 1295-1303.
166. Betts, C.; Saleh, A.F.; Arzumanov, A.A.; Hammond, S.M.; Godfrey, C.; Coursindel, T.; Gait, M.J.; Wood, M.J. Pip6-PMO, A New Generation of Peptide-oligonucleotide Conjugates With Improved Cardiac Exon Skipping Activity for DMD Treatment. Mol. Ther. Nucleic Acids 2012, 1, e38.
167. Betts, C.A.; Saleh, A.F.; Carr, C.A.; Hammond, S.M.; Coenen-Stass, A.M.L.; Godfrey, C.; McClorey, G.; Varela, M.A.; Roberts, T.C.; Clarke, K.; et al. Prevention of exercise induced cardiomyopathy following Pip-PMO treatment in dystrophic mdx mice. Sci. Rep. 2015, 5, 8986.
168. Samoylova, T.I.; Smith, B.F. Elucidation of muscle-binding peptides by phage display screening. Muscle Nerve 1999, 22, 460-466.
169. Yin, H.; Lu, Q.; Wood, M. Effective exon skipping and restoration of dystrophin expression by peptide nucleic acid antisense oligonucleotides in mdx mice. Mol. Ther 2008 16 38-45.
170. Yin, H.; Moulton, H.M.; Betts, C.; Seow, Y.; Boutilier, J.; Iverson, P.L.; Wood, M.J.A. A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice. Hum. Mol. Genet. 2009, 18, 4405-4414.
171. Seow, Y.; Yin, H.; Wood, M.J.A. Identification of a novel muscle targeting peptide in mdx mice. Peptides 2010, 31, 1873-1877.
172. Jirka, S.M.G.; Heemskerk, H.; Tanganyika-de Winter, C.L.; Muilwijk, D.; Pang, K.H.; de Visser, P.C.; Janson, A.; Karnaoukh, T.G.; Vermue, R.; 't Hoen, P.A.C.; et al. Peptide Conjugation of 2?-O-methyl Phosphorothioate Antisense Oligonucleotides Enhances Cardiac Uptake and Exon Skipping in mdx Mice. Nucleic Acid Ther. 2014, 24, 25-36.
173. Rybakova, I.N.; Ervasti, J.M. Identification of spectrin-like repeats required for high affinity utrophin-Actin interaction. J. Biol. Chem. 2005, 280, 23018-23023.
174. Fairclough, R.J.; Bareja, A.; Davies, K.E. Progress in therapy for Duchenne muscular dystrophy. Exp. Physiol. 2011, 96, 1101-1113.
175. Tinsley, J.M.; Blake, D.J.; Roche, A.; Fairbrother, U.; Riss, J.; Byth, B.C.; Knight, A.E.; Kendrick-Jones, J.; Suthers, G.K.; Love, D.R. Primary structure of dystrophin-related protein. Nature 1992, 360, 591-593.
176. Ishikawa-Sakurai, M.; Yoshida, M.; Imamura, M.; Davies, K.E.; Ozawa, E. ZZ domain is essentially required for the physiological binding of dystrophin and utrophin to beta-dystroglycan. Hum. Mol. Genet 2004 13 693-702.
177. Deconinck, N.; Rafael, J.A.; Beckers-Bleukx, G.; Kahn, D.; Deconinck, A.E.; Davies, K.E.; Gillis, J.M. Consequences of the combined deficiency in dystrophin and utrophin on the mechanical properties and myosin composition of some limb and respiratory muscles of the mouse. Neuromuscul. Disord. 1998, 8, 362-370.
178. Verhaart, I.E.C.; van Duijn, R.J.M.; den Adel, B.; Roest, A.A.W.; Verschuuren, J.J.G.M.; Aartsma-Rus, A.; van der Weerd, L. Assessment of cardiac function in three mouse dystrophinopathies by magnetic resonance imaging. Neuromuscul. Disord. 2012, 22, 418-426.
179. Chun, J.L.; O'Brien, R.; Berry, S.E. Cardiac dysfunction and pathology in the dystrophin and utrophin-deficient mouse during development of dilated cardiomyopathy. Neuromuscul. Disord. 2012, 22, 368-379.
180. Fairclough, R.J.; Wood, M.J.; Davies, K.E. Therapy for Duchenne muscular dystrophy: Renewed optimism from genetic approaches. Nat. Rev. Genet. 2013, 14, 373-378.
181. Finkel, R.S. Read-Through strategies for suppression of nonsense mutations in Duchenne/Becker muscular dystrophy: Aminoglycosides and ataluren (PTC124). J. Child Neurol. 2010, 25, 1158-1164.
182. Konieczny, P.; Swiderski, K.; Chamberlain, J.S. Gene and cell-mediated therapies for muscular dystrophy. Muscle Nerve 2013, 47, 649-663.
183. Muntoni, F.; Wood, M.J. A Targeting RNA to treat neuromuscular disease. Nat. Rev. Drug Discov. 2011, 10, 621-637.
184. Scott, J.M.; Li, S.; Harper, S.Q.; Welikson, R.; Bourque, D.; DelloRusso, C.; Hauschka, S.D.; Chamberlain, J.S. Viral vectors for gene transfer of micro-, mini-, or full-length dystrophin. Neuromuscul. Disord. 2002, 12, 23-29.
185. Asokan, A.; Schaffer, D.V.; Samulski, R.J. The AAV Vector Toolkit: Poised at the Clinical Crossroads. Mol. Ther. 2012, 20, 699-708.
186. Mendell, J.R.; Rodino-Klapac, L.; Sahenk, Z.; Malik, V.; Kaspar, B.K.; Walker, C.M.; Clark, K.R. Gene therapy for muscular dystrophy: Lessons learned and path forward. Neurosci. Lett. 2012, 527, 90-99.
187. Foster, H.; Popplewell, L.; Dickson, G. Genetic Therapeutic Approaches for Duchenne Muscular Dystrophy. Hum. Gene Ther. 2012, 23, 676-687.
188. Wang, Z.; Kuhr, C.S.; Allen, J.M.; Blankinship, M.; Gregorevic, P.; Chamberlain, J.S.; Tapscott, S.J.; Storb, R. Sustained AAV-mediated dystrophin expression in a canine model of Duchenne muscular dystrophy with a brief course of immunosuppression. Mol. Ther. 2007, 15, 1160-1166.
189. Skuk, D.; Goulet, M.; Roy, B.; Tremblay, J.P. Efficacy of myoblast transplantation in nonhuman primates following simple intramuscular cell injections: Toward defining strategies applicable to humans. Exp. Neurol. 2002, 175, 112-126.
190. Huard, C.; Moisset, P.A.; Dicaire, A.; Merly, F.; Tardif, F.; Asselin, I.; Tremblay, J.P. Transplantation of dermal fibroblasts expressing MyoD1 in mouse muscles. Biochem. Biophys. Res. Commun. 1998, 248, 648-654.
191. Goodell, M.A.; Brose, K.; Paradis, G.; Conner, A.S.; Mulligan, R.C. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 1996, 183, 1797-1806.
192. Rousseau, J.; Chapdelaine, P.; Boisvert, S.; Almeida, L.P.; Corbeil, J.; Montpetit, A.; Tremblay, J.P. Endonucleases: Tools to correct the dystrophin gene. J. Gene Med. 2011, 13, 522-537.
193. Li, H.L.; Fujimoto, N.; Sasakawa, N.; Shirai, S.; Ohkame, T.; Sakuma, T.; Tanaka, M.; Amano, N.; Watanabe, A.; Sakurai, H.; et al. Precise Correction of the Dystrophin Gene in Duchenne Muscular Dystrophy Patient Induced Pluripotent Stem Cells by TALEN and CRISPR-Cas9. Stem Cell Rep. 2015, 4, 143-154.
194. Alberts, B.; Johnson, A.; Lewis, J.; Morgan, D.; Raff, M.; Roberts, K.; Walter, P. Molecular Biology of the Cell, 6th ed.; Garland Science: New York, NY, USA, 2014.
195. Popplewell, L.; Koo, T.; Leclerc, X.; Duclert, A.; Mamchaoui, K.; Gouble, A.; Mouly, V.; Voit, T.; Pâques, F.; Cédrone, F.; et al. Gene correction of a duchenne muscular dystrophy mutation by meganuclease-enhanced exon knock-in. Hum. Gene Ther. 2013, 24, 692-701.
196. Wilton, S.D.; Lloyd, F.; Carville, K.; Fletcher, S.; Honeyman, K.; Agrawal, S.; Kole, R. Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides. Neuromuscul. Disord. 1999, 9, 330-338.
197. Cartegni, L.; Chew, S.L.; Krainer, A.R. Listening to silence and understanding nonsense: Exonic mutations that affect splicing. Nat. Rev. Genet. 2002, 3, 285-298.
198. Aartsma-Rus, A.; Fokkema, I.; Verschuuren, J.; Ginjaar, I.; van Deutekom, J.; van Ommen, G.J.; den Dunnen, J.T. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum. Mutat. 2009, 30, 293-299.
199. Voit, T.; Topaloglu, H.; Straub, V.; Muntoni, F.; Deconinck, N.; Campion, G.; de Kimpe, S.J.; Eagle, M.; Guglieri, M.; Hood, S.; et al. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): An exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014, 13, 987-996.
200. Malerba, A.; Thorogood, F.C.; Dickson, G.; Graham, I.R. Dosing regimen has a significant impact on the efficiency of morpholino oligomer-induced exon skipping in mdx mice. Hum. Gene Ther. 2009, 20, 955-965.
201. Malerba, A.; Sharp, P.S.; Graham, I.R.; Arechavala-Gomeza, V.; Foster, K.; Muntoni, F.; Wells, D.J.; Dickson, G. Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx mice. Mol. Ther. 2011, 19, 345-354.
202. Negishi, Y.; Hamano, N.; Shiono, H.; Akiyama, S.; Endo-Takahashi, Y.; Suzuki, R.; Maruyama, K.; Aramaki, Y. The development of an ultrasound-mediated nucleic acid delivery system for treating muscular dystrophies. Yakugaku Zasshi 2012, 132, 1383-1388.
203. Bestas, B.; McClorey, G.; Tedebark, U.; Moreno, P.M.D.; Roberts, T.C.; Hammond, S.M.; Smith, C.I.E.; Wood, M.J.A.; Andaloussi, S. El Design and application of bispecific splice-switching oligonucleotides. Nucleic Acid Ther. 2014, 24, 13-24.