Tadalafil alleviates muscle ischemia in patients with becker muscular dystrophy

Science Translational Medicine

Volumn 4, Issue 162, 2012, Pages

  Martin, Elizabeth A ^a   Barresi, Rita ^b   Byrne, Barry J ^c   Tsimerinov, Evgeny I ^a   Scott, Bryan L ^a   Walker, Ashley E ^a   Gurudevan, Swaminatha V ^a   Anene, Francine ^d   Elashoff, Robert M ^d,e   Thomas, Gail D ^a   Victor, Ronald G ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

^c UNIVERSITY OF FLORIDA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC GMP; DYSTROPHIN; NITRIC OXIDE SYNTHASE; PLACEBO; TADALAFIL;

ADULT; ARTICLE; BECKER MUSCULAR DYSTROPHY; CLINICAL ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG MECHANISM; EXERCISE; GENE DISRUPTION; GENE MUTATION; HUMAN; HUMAN TISSUE; MALE; MUSCLE BLOOD FLOW; MUSCLE ISCHEMIA; NEUROPROTECTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SARCOLEMMA; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SYMPATHETIC REFLEX; TARGET ORGAN; TISSUE OXYGENATION; VASOCONSTRICTION;

ADOLESCENT; ADULT; ANIMALS; BIOPSY; CARBOLINES; CHILD; CHILD, PRESCHOOL; HUMANS; IMMUNOHISTOCHEMISTRY; ISCHEMIA; MALE; MICE; MIDDLE AGED; MUSCLE, SKELETAL; MUSCULAR DYSTROPHY, DUCHENNE; PHOSPHODIESTERASE 5 INHIBITORS; SYMPATHOLYTICS; YOUNG ADULT;

EID: 84870365475     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3004327     Document Type: Article

References (61)

1. K. Bushby, R. Finkel, D. J. Birnkrant, L. E. Case, P. R. Clemens, L. Cripe, A. Kaul, K. Kinnett, C. McDonald, S. Pandya, J. Poysky, F. Shapiro, J. Tomezsko, C. Constantin; DMD Care Considerations Working Group, Diagnosis and management of Duchenne muscular dystrophy, part 1: Diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9, 77-93 (2010).
2. K. Bushby, R. Finkel, D. J. Birnkrant, L. E. Case, P. R. Clemens, L. Cripe, A. Kaul, K. Kinnett, C. McDonald, S. Pandya, J. Poysky, F. Shapiro, J. Tomezsko, C. Constantin; DMD Care Considerations Working Group, Diagnosis and management of Duchenne muscular dystrophy, part 2: Implementation of multidisciplinary care. Lancet Neurol. 9, 177-189 (2010).
3. A. E. Emery, The muscular dystrophies. Lancet 359, 687-695 (2002).
4. M. Koenig, A. H. Beggs, M. Moyer, S. Scherpf, K. Heindrich, T. Bettecken, G. Meng, C. R. Müller, M. Lindlöf, H. Kaariainen, A. de la Chapelle, A. Kiuru, M.-L. Savontaus, H. Gilgenkrantz, D. Récan, J. Chelly, J.-C. Kaplan, A. E. Covone, N. Archidiacono, G. Romeo, S. Liechti-Gallati, V. Schneider, S. Braga, H. Moser, B. T. Darras, P. Murphy, U. Francke, J. D. Chen, G. Morgan, M. Denton, C. R. Greenberg, K. Wrogemann, L. A. J. Blonden, H. M. B. van Paassen, G. J. B. van Ommen, L. M. Kunkel, The molecular basis for Duchenne versus Becker muscular dystrophy: Correlation of severity with type of deletion. Am. J. Hum. Genet. 45, 498-506 (1989).
5. A. P. Monaco, C. J. Bertelson, S. Liechti-Gallati, H. Moser, L. M. Kunkel, An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2, 90-95 (1988).
6. D. Duan, Duchenne muscular dystrophy gene therapy: Lost in translation? Res. Rep. Biol. 2011, 31-42 (2011).
7. D. J. Blake, A. Weir, S. E. Newey, K. E. Davies, Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol. Rev. 82, 291-329 (2002).
8. B. J. Petrof, J. B. Shrager, H. H. Stedman, A. M. Kelly, H. L. Sweeney, Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc. Natl. Acad. Sci. U.S.A. 90, 3710-3714 (1993).
9. J. E. Brenman, D. S. Chao, H. Xia, K. Aldape, D. S. Bredt, Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82, 743-752 (1995).
10. W. J. Chang, S. T. Iannaccone, K. S. Lau, B. S. Masters, T. J. McCabe, K. McMillan, R. C. Padre, M. J. Spencer, J. G. Tidball, J. T. Stull, Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proc. Natl. Acad. Sci. U.S.A. 93, 9142-9147 (1996).
11. Y. Lai, G. D. Thomas, Y. Yue, H. T. Yang, D. Li, C. Long, L. Judge, B. Bostick, J. S. Chamberlain, R. L. Terjung, D. Duan, 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. Invest. 119, 624-635 (2009).
12. B. Chavoshan, M. Sander, T. E. Sybert, J. Hansen, R. G. Victor, G. D. Thomas, Nitric oxide-dependent modulation of sympathetic neural control of oxygenation in exercising human skeletal muscle. J. Physiol. 540, 377-386 (2002).
13. J. Hansen, G. D. Thomas, S. A. Harris, W. J. Parsons, R. G. Victor, Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle. J. Clin. Invest. 98, 584-596 (1996).
14. M. Sander, B. Chavoshan, S. A. Harris, S. T. Iannaccone, J. T. Stull, G. D. Thomas, R. G. Victor, Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. U.S.A. 97, 13818-13823 (2000).
15. G. D. Thomas, J. Hansen, R. G. Victor, Inhibition of alpha 2-adrenergic vasoconstriction during contraction of glycolytic, not oxidative, rat hindlimb muscle. Am. J. Physiol. 266, H920-H929 (1994).
16. G. D. Thomas, M. Sander, K. S. Lau, P. L. Huang, J. T. Stull, R. G. Victor, Impaired metabolic modulation of α-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. Proc. Natl. Acad. Sci. U.S.A. 95, 15090-15095 (1998).
17. G. D. Thomas, R. G. Victor, Nitric oxide mediates contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. J. Physiol. 506 (Pt. 3), 817-826 (1998).
18. G. D. Thomas, W. Zhang, R. G. Victor, Impaired modulation of sympathetic vasoconstriction in contracting skeletal muscle of rats with chronic myocardial infarctions: Role of oxidative stress. Circ. Res. 88, 816-823 (2001).
19. G. D. Thomas, P. W. Shaul, I. S. Yuhanna, S. C. Froehner, M. E. Adams, Vasomodulation by skeletal muscle-derived nitric oxide requires α-syntrophin-mediated sarcolemmal localization of neuronal nitric oxide synthase. Circ. Res. 92, 554-560 (2003).
20. W. Vongpatanasin, Z. Wang, D. Arbique, G. Arbique, B. Adams-Huet, J. H. Mitchell, R. G. Victor, G. D. Thomas, Functional sympatholysis is impaired in hypertensive humans. J. Physiol. 589, 1209-1220 (2011).
21. B. G. Wallin, R. G. Victor, A. L. Mark, Sympathetic outflow to resting muscles during static handgrip and postcontraction muscle ischemia. Am. J. Physiol. 256, H105-H110 (1989).
22. M. Wehling-Henricks, M. C. Jordan, K. P. Roos, B. Deng, J. G. Tidball, Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Hum. Mol. Genet. 14, 1921-1933 (2005).
23. M. Wehling, M. J. Spencer, J. G. Tidball, A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. J. Cell Biol. 155, 123-131 (2001).
24. E. R. Barton, L. Morris, M. Kawana, L. T. Bish, T. Toursel, Systemic administration of L-arginine benefits mdx skeletal muscle function. Muscle Nerve 32, 751-760 (2005).
25. V. Voisin, C. Sébrié, S. Matecki, H. Yu, B. Gillet, M. Ramonatxo, M. Israël, S. De la Porte, L-arginine improves dystrophic phenotype in mdx mice. Neurobiol. Dis. 20, 123-130 (2005).
26. S. Brunelli, C. Sciorati, G. D'Antona, A. Innocenzi, D. Covarello, B. G. Galvez, C. Perrotta, A. Monopoli, F. Sanvito, R. Bottinelli, E. Ongini, G. Cossu, E. Clementi, Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy. Proc. Natl. Acad. Sci. U.S.A. 104, 264-269 (2007).
27. C. Sciorati, D. Miglietta, R. Buono, V. Pisa, D. Cattaneo, E. Azzoni, S. Brunelli, E. Clementi, 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, 210-217 (2011).
28. A. Asai, N. Sahani, M. Kaneki, Y. Ouchi, J. A. Martyn, S. E. Yasuhara, Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phosphodiesterase-5 inhibitor therapy in mouse muscular dystrophy. PLoS One 2, e806 (2007).
29. Y. M. Kobayashi, E. P. Rader, R. W. Crawford, N. K. Iyengar, D. R. Thedens, J. A. Faulkner, S. V. Parikh, R. M. Weiss, J. S. Chamberlain, S. A. Moore, K. P. Campbell, Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature 456, 511-515 (2008).
30. C. M. Adamo, D. F. Dai, J. M. Percival, E. Minami, M. S. Willis, E. Patrucco, S. C. Froehner, J. A. Beavo, Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. U.S.A. 107, 19079-19083 (2010).
31. M. Khairallah, R. J. Khairallah, M. E. Young, B. G. Allen, M. A. Gillis, G. Danialou, C. F. Deschepper, B. J. Petrof, C. Des Rosiers, Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. Proc. Natl. Acad. Sci. U.S.A. 105, 7028-7033 (2008).
32. G. Kawahara, J. A. Karpf, J. A. Myers, M. S. Alexander, J. R. Guyon, L. M. Kunkel, Drug screening in a zebrafish model of Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. U.S.A. 108, 5331-5336 (2011).
33. D. S. Chao, J. R. Gorospe, J. E. Brenman, J. A. Rafael, M. F. Peters, S. C. Froehner, E. P. Hoffman, J. S. Chamberlain, D. S. Bredt, Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy. J. Exp. Med. 184, 609-618 (1996).
34. S. Torelli, S. C. Brown, C. Jimenez-Mallebrera, L. Feng, F. Muntoni, C. A. Sewry, Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions. Neuropathol. Appl. Neurobiol. 30, 540-545 (2004).
35. K. E. Wells, S. Torelli, Q. Lu, S. C. Brown, T. Partridge, F. Muntoni, D. J. Wells, Relocalization of neuronal nitric oxide synthase (nNOS) as a marker for complete restoration of the dystrophin associated protein complex in skeletal muscle. Neuromuscul. Disord. 13, 21-31 (2003).
36. A. Romfh, E. M. McNally, Cardiac assessment in Duchenne and Becker muscular dystrophies. Curr. Heart Fail. Rep. 7, 212-218 (2010).
37. W. Zhao, S. A. Swanson, J. Ye, X. Li, J. M. Shelton, W. Zhang, G. D. Thomas, Reactive oxygen species impair sympathetic vasoregulation in skeletal muscle in angiotensin II-dependent hypertension. Hypertension 48, 637-643 (2006).
38. P. Bagher, D. Duan, S. S. Segal, Evidence for impaired neurovascular transmission in a murine model of Duchenne muscular dystrophy. J. Appl. Physiol. 110, 601-609 (2011).
39. J. H. Lombard, Microcirculation in a mouse model of Duchenne muscular dystrophy: Another blow to the vascular hypothesis? J. Appl. Physiol. 110, 587-588 (2011).
40. C. Gentil, F. Leturcq, R. Ben Yaou, J. C. Kaplan, P. Laforet, I. Pénisson-Besnier, C. Espil-Taris, T. Voit, L. Garcia, F. Piétri-Rouxel, Variable phenotype of del45-55 Becker patients correlated with nNOSμ mislocalization and RYR1 hypernitrosylation. Hum. Mol. Genet. 21, 3449-3460 (2012).
41. V. Palit, I. Eardley, An update on new oral PDE5 inhibitors for the treatment of erectile dysfunction. Nat. Rev. Urol. 7, 603-609 (2010).
42. G. Ravipati, J. A. McClung, W. S. Aronow, S. J. Peterson, W. H. Frishman, Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease. Cardiol. Rev. 15, 76-86 (2007).
43. R. W. Kaspar, H. D. Allen, W. C. Ray, C. E. Alvarez, J. T. Kissel, A. Pestronk, R. B. Weiss, K. M. Flanigan, J. R. Mendell, F. Montanaro, Analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in Becker muscular dystrophy. Circ. Cardiovasc. Genet. 2, 544-551 (2009).
44. P. J. Fadel, M. Farias III, K. M. Gallagher, Z. Wang, G. D. Thomas, Oxidative stress and enhanced sympathetic vasoconstriction in contracting muscles of nitrate-tolerant rats and humans. J. Physiol. 590, 395-407 (2012).
45. J. M. Percival, K. N. Anderson, P. Huang, M. E. Adams, S. C. Froehner, Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle. J. Clin. Invest. 120, 816-826 (2010).
46. K. Anthony, S. Cirak, S. Torelli, G. Tasca, L. Feng, V. Arechavala-Gomeza, A. Armaroli, M. Guglieri, C. S. Straathof, J. J. Verschuuren, A. Aartsma-Rus, P. Helderman-van den Enden, K. Bushby, V. Straub, C. Sewry, A. Ferlini, E. Ricci, J. E. Morgan, F. Muntoni, Dystrophin quantification and clinical correlations in Becker muscular dystrophy: Implications for clinical trials. Brain 134, 3547-3559 (2011).
47. E. L. Finanger Hedderick, J. L. Simmers, A. Soleimani, E. Andres-Mateos, R. Marx, D. C. Files, L. King, T. O. Crawford, A. M. Corse, R. D. Cohn, Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders. Neurology 76, 960-967 (2011).
48. NIH RePORT, Planning a multicenter trial of PDE5A inhibition for Duchenne muscular dystrophy, http://projectreporter.nih.gov/project-info-description. cfm?aid=8295579&icde=13915249amp;ddparam=&ddvalue=&ddsub=&cr= 1&csb=default&cs=ASC [accessed 26 September 2012].
49. S. Cirak, V. Arechavala-Gomeza, M. Guglieri, L. Feng, S. Torelli, K. Anthony, S. Abbs, M. E. Garralda, J. Bourke, D. J. Wells, G. Dickson, M. J. Wood, S. D. Wilton, V. Straub, R. Kole, S. B. Shrewsbury, C. Sewry, J. E. Morgan, K. Bushby, F. Muntoni, 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 378, 595-605 (2011).
50. S. Cirak, L. Feng, K. Anthony, V. Arechavala-Gomeza, S. Torelli, C. Sewry, J. E. Morgan, F. Muntoni, Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy. Mol. Ther. 20, 462-467 (2012).
51. N. Suzuki, N. Motohashi, A. Uezumi, S. Fukada, T. Yoshimura, Y. Itoyama, M. Aoki, Y. Miyagoe-Suzuki, S. Takeda, NO production results in suspension-induced muscle atrophy through dislocation of neuronal NOS. J. Clin. Invest. 117, 2468-2476 (2007).
52. F. Zeng, Z. R. Ren, S. Z. Huang, M. Kalf, M. Mommersteeg, M. Smit, S. White, C. L. Jin, M. Xu, D. W. Zhou, J. B. Yan, M. J. Chen, R. van Beuningen, S. Z. Huang, J. den Dunnen, Y. T. Zeng, Y. Wu, Array-MLPA: Comprehensive detection of deletions and duplications and its application to DMD patients. Hum. Mutat. 29, 190-197 (2008).
53. T. Lalic, R. H. Vossen, J. Coffa, J. P. Schouten, M. Guc-Scekic, D. Radivojevic, M. Djurisic, M. H. Breuning, S. J. White, J. T. den Dunnen, Deletion and duplication screening in the DMD gene using MLPA. Eur. J. Hum. Genet. 13, 1231-1234 (2005).
54. K. M. Flanigan, A. von Niederhausern, D. M. Dunn, J. Alder, J. R. Mendell, R. B. Weiss, Rapid direct sequence analysis of the dystrophin gene. Am. J. Hum. Genet. 72, 931-939 (2003).
55. E. Gratton, S. Fantini, M. A. Franceschini, G. Gratton, M. Fabiani, Measurements of scattering and absorption changes in muscle and brain. Philos. Trans. R. Soc. Lond. B Biol. Sci. 352, 727-735 (1997).
56. F. F. Jöbsis, Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198, 1264-1267 (1977).
57. R. G. Victor, D. R. Seals, A. L. Mark, Differential control of heart rate and sympathetic nerve activity during dynamic exercise. Insight from intraneural recordings in humans. J. Clin. Invest. 79, 508-516 (1987).
58. T. N. Jacobsen, B. J. Morgan, U. Scherrer, S. F. Vissing, R. A. Lange, N. Johnson, W. S. Ring, P. S. Rahko, P. Hanson, R. G. Victor, Relative contributions of cardiopulmonary and sinoaortic baroreflexes in causing sympathetic activation in the human skeletal muscle circulation during orthostatic stress. Circ. Res. 73, 367-378 (1993).
59. R. G. Victor, W. N. Leimbach Jr., Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans. J. Appl. Physiol. 63, 2558-2562 (1987).
60. S. F. Vissing, U. Scherrer, R. G. Victor, Relation between sympathetic outflow and vascular resistance in the calf during perturbations in central venous pressure. Evidence for cardiopulmonary afferent regulation of calf vascular resistance in humans. Circ. Res. 65, 1710-1717 (1989).
61. L. V. Anderson, K. Davison, Multiplex Western blotting system for the analysis of muscular dystrophy proteins. Am. J. Pathol. 154, 1017-1022 (1999).