Gene therapy for Duchenne muscular dystrophy

Current Opinion in Neurology

Volumn 25, Issue 5, 2012, Pages 588-596

  Verhaart, Ingrid E C ^a   Aartsma Rus, Annemieke ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Duchenne muscular dystrophy; exon skipping; gene therapy; therapy

Indexed keywords

2' O METHYL PHOSPHOROTHIOATE RNA; ADENOVIRUS VECTOR; ANTISENSE OLIGONUCLEOTIDE; ATALUREN; DYSTROPHIN; GENTAMICIN; MORPHOLINO OLIGONUCLEOTIDE; PLACEBO; UNCLASSIFIED DRUG;

CODON; DISEASE COURSE; DISEASE SEVERITY; DRUG DOSE ESCALATION; DRUG EFFICACY; DUCHENNE MUSCULAR DYSTROPHY; EXON; GENE DELIVERY SYSTEM; GENE MUTATION; GENE THERAPY; GENE TRANSFER; HUMAN; MUSCLE BIOPSY; NONHUMAN; OUTCOME ASSESSMENT; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SINGLE DRUG DOSE; THERAPY EFFECT;

ANIMALS; CLINICAL TRIALS AS TOPIC; CODON, TERMINATOR; EXONS; GENETIC THERAPY; HUMANS; MUSCLE, SKELETAL; MUSCULAR DYSTROPHY, DUCHENNE; OLIGONUCLEOTIDES, ANTISENSE; TREATMENT OUTCOME;

EID: 84866342088     PISSN: 13507540     EISSN: 14736551     Source Type: Journal    
DOI: 10.1097/WCO.0b013e328357b0be     Document Type: Review

References (83)

1. Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol 2003; 2:731-740. (Pubitemid 37443515)
2. Goyenvalle A, Seto JT, Davies KE, Chamberlain J. Therapeutic approaches to muscular dystrophy. Hum Mol Genet 2011; 20:R69-R78.
3. Hammond SM, Wood MJ. Genetic therapies for RNA mis-splicing diseases. Trends Genet 2011; 27:196-205.
4. Muntoni F, Wood MJ. Targeting RNA to treat neuromuscular disease. Nat Rev Drug Discov 2011; 10:621-637.
5. Monaco AP, Bertelson CJ, Liechti-Gallati S, et al. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 1988; 2:90-95.
6. Aartsma-Rus A. Antisense-mediated modulation of splicing: therapeutic implications for Duchenne muscular dystrophy. RNA Biol 2010; 7.
7. Aartsma-Rus A, Fokkema I, Verschuuren J, et al. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat 2009; 30:293-299.
8. Kinali M, Arechavala-Gomeza V, Feng L, 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.
9. van Deutekom JC, Janson AA, Ginjaar IB, et al. Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med 2007; 357:2677-2686.
10. Cirak S, Arechavala-Gomeza V, Guglieri M, 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.
11. Goemans NM, Tulinius M, van den Akker JT, et al. Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med 2011; 364:1513-1522.
12. Malerba A, Boldrin L, Dickson G. Long-term systemic administration of unconjugated morpholino oligomers for therapeutic expression of dystrophin by exon skipping in skeletal muscle: implications for cardiac muscle integrity. Nucleic Acid Ther 2011; 21:293-298.
13. Malerba A, Sharp PS, Graham IR, et al. Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx mice. Mol Ther 2011; 19:345-354.
14. Heemskerk H, de WC, van KP, et al. Preclinical PK and PD studies on 2'-O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model. Mol Ther 2010; 18:1210-1217.
15. Heemskerk HA, de Winter CL, de Kimpe SJ, et al. In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J Gene Med 2009; 11:257-266.
16. Alter J, Lou F, Rabinowitz A, et al. Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nat Med 2006; 12:175-177. (Pubitemid 43214742)
17. Wu B, Xiao B, Cloer C, et al. One-year treatment of morpholino antisense oligomer improves skeletal and cardiac muscle functions in dystrophic mdx mice. Mol Ther 2011; 19:576-583.
18. Wu B, Benrashid E, Lu P, et al. Targeted skipping of human dystrophin exons in transgenic mouse model systemically for antisense drug development. PLoS One 2011; 6:e19906.
19. Yin H, Saleh AF, Betts C, 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.
20. Yin H, Moulton H, Betts C, Wood M. CPP-directed oligonucleotide exon skipping in animal models of Duchenne muscular dystrophy. Methods Mol Biol 2011; 683:321-338.
21. Moulton HM, Moulton JD. Morpholinos and their peptide conjugates: therapeutic promise and challenge for Duchenne muscular dystrophy. Biochim Biophys Acta 2010; 1798:2296-2303.
22. Muntoni F. The development of antisense oligonucleotide therapies for Duchenne muscular dystrophy: report on a TREAT-NMD workshop hosted by the European Medicines Agency (EMA), on September 25th 2009. Neuromuscul Disord 2010; 20:355-362.
23. Romero NB, Braun S, Benveniste O, et al. Phase I study of dystrophin plasmid-based gene therapy in Duchenne/Becker muscular dystrophy. Hum Gene Ther 2004; 15:1065-1076. (Pubitemid 39552288)
24. van Deutekom JC, van Ommen GJ. Advances in Duchenne muscular dystrophy gene therapy. Nat Rev Genet 2003; 4:774-783. (Pubitemid 37193269)
25. Banks GB, Gregorevic P, Allen JM, et al. Functional capacity of dystrophins carrying deletions in the N-terminal actin-binding domain. Hum Mol Genet 2007; 16:2105-2113. (Pubitemid 47354893)
26. Blankinship MJ, Gregorevic P, Chamberlain JS. Gene therapy strategies for Duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors. Mol Ther 2006; 13:241-249. (Pubitemid 43056889)
27. Gregorevic P, Blankinship MJ, Allen JM, et al. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med 2004; 10:828-834. (Pubitemid 39070856)
28. Gregorevic P, Blankinship MJ, Allen JM, Chamberlain JS. Systemic microdystrophin gene delivery improves skeletal muscle structure and function in old dystrophic mdx mice. Mol Ther 2008; 16:657-664. (Pubitemid 351426166)
29. Liu M, Yue Y, Harper SQ, et al. Adeno-associated virus-mediated microdystrophin expression protects young mdx muscle from contraction-induced injury. Mol Ther 2005; 11:245-256.
30. Bowles DE, McPhee SW, Li C, et al. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther 2012; 20:443-455.
31. Mendell JR, Campbell K, Rodino-Klapac L, et al. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med 2010; 363:1429-1437.
32. Denti MA, Incitti T, Sthandier O, et al. Long-term benefit of adeno-associated virus/antisense-mediated exon skipping in dystrophic mice. Hum Gene Ther 2008; 19:601-608. (Pubitemid 351913531)
33. Denti MA, Rosa A, D'Antona G, et al. Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model. Proc Natl Acad Sci USA 2006; 103:3758-3763. (Pubitemid 43376628)
34. Goyenvalle A, Vulin A, Fougerousse F, et al. Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 2004; 306:1796-1799. (Pubitemid 39601401)
35. De Angelis FG, Sthandier O, Berarducci B, et al. Chimeric snRNA molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin premRNA induce exon skipping and restoration of a dystrophin synthesis in Delta 48-50 DMD cells. Proc Natl Acad Sci USA 2002; 99:9456-9461. (Pubitemid 34764635)
36. Goyenvalle A, Babbs A, Wright J, et al. Rescue of severely affected dystrophin/utrophin-deficient mice through scAAV-U7snRNA-mediated exon skipping. Hum Mol Genet 2012; 21:2559-2571.
37. Goyenvalle A, Wright J, Babbs A, et al. Engineering multiple U7snRNA constructs to induce single and multiexon-skipping for Duchenne muscular dystrophy. Mol Ther 2012; 20:1212-1221.
38. Incitti T, De Angelis FG, Cazzella V, et al. Exon skipping and Duchenne muscular dystrophy therapy: selection of the most active U1 snRNA antisense able to induce dystrophin exon 51 skipping. Mol Ther 2010; 18:1675-1682.
39. Ghosh A, Yue Y, Shin JH, Duan D. Systemic trans-splicing adeno-associated viral delivery efficiently transduces the heart of adult mdx mouse, a model for Duchenne muscular dystrophy. Hum Gene Ther 2009; 20:1319-1328.
40. Odom GL, Gregorevic P, Allen JM, Chamberlain JS. Gene therapy of mdx mice with large truncated dystrophins generated by recombination using rAAV6. Mol Ther 2011; 19:36-45.
41. Zhang Y, Duan D. Novel mini-dystrophin gene dual adeno-associated virus vectors restore neuronal nitric oxide synthase expression at the sarcolemma. Hum Gene Ther 2012; 23:98-103.
42. Ishizaki M, Maeda Y, Kawano R, et al. Rescue from respiratory dysfunction by transduction of full-length dystrophin to diaphragm via the peritoneal cavity in utrophin/dystrophin double knockout mice. Mol Ther 2011; 19:1230-1235.
43. Yuasa K, Yoshimura M, Urasawa N, et al. Injection of a recombinant AAV serotype 2 into canine skeletal muscles evokes strong immune responses against transgene products. Gene Ther 2007; 14:1249-1260. (Pubitemid 47299950)
44. Mays LE, Wilson JM. The complex and evolving story of T cell activation to AAV vector-encoded transgene products. Mol Ther 2011; 19:16-27.
45. Tang Y, Cummins J, Huard J, Wang B. AAV-directed muscular dystrophy gene therapy. Expert Opin Biol Ther 2010; 10:395-408.
46. Zaiss AK, Muruve DA. Immune responses to adeno-associated virus vectors. Curr Gene Ther 2005; 5:323-331. (Pubitemid 40895016)
47. Koo T, Okada T, Athanasopoulos T, et al. Long-term functional adenoassociated virus-microdystrophin expression in the dystrophic CXMDj dog. J Gene Med 2011; 13:497-506.
48. Shin JH, Yue Y, Srivastava A, et al. A simplified immune suppression scheme leads to persistent micro-dystrophin expression in Duchenne muscular dystrophy dogs. Hum Gene Ther 2012; 23:202-209.
49. Zincarelli C, Soltys S, Rengo G, et al. Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart. Clin Transl Sci 2010; 3:81-89.
50. Evans VC, Graham IR, Athanasopoulos T, et al. Adeno-associated virus serotypes 7 and 8 outperform serotype 9 in expressing atheroprotective human apoE3 from mouse skeletal muscle. Metabolism 2011; 60:491-498.
51. Gao G, Bish LT, Sleeper MM, et al. Transendocardial delivery of AAV6 results in highly efficient and global cardiac gene transfer in rhesus macaques. Hum Gene Ther 2011; 22:979-984.
52. Moulay G, Boutin S, Masurier C, et al. Polymers for improving the in vivo transduction efficiency of AAV2 vectors. PLoS One 2010; 5:e15576.
53. Hegge JO, Wooddell CI, Zhang G, et al. Evaluation of hydrodynamic limb vein injections in nonhuman primates. Hum Gene Ther 2010; 21:829-842.
54. Wooddell CI, Hegge JO, Zhang G, et al. Dose response in rodents and nonhuman primates after hydrodynamic limb vein delivery of naked plasmid DNA. Hum Gene Ther 2011; 22:889-903.
55. Qiao C, Li J, Zheng H, et al. Hydrodynamic limb vein injection of adenoassociated virus serotype 8 vector carrying canine myostatin propeptide gene into normal dogs enhances muscle growth. Hum Gene Ther 2009; 20:1-10.
56. Zhang G, Wooddell CI, Hegge JO, et al. Functional efficacy of dystrophin expression from plasmids delivered to mdx mice by hydrodynamic limb vein injection. Hum Gene Ther 2010; 21:221-237.
57. Fan Z, Kocis K, Valley R, et al. Safety and feasibility of high-pressure transvenous limb perfusion with 0.9% saline in human muscular dystrophy. Mol Ther 2012; 20:456-461.
58. Bish LT, Sleeper MM, Forbes SC, et al. Long-term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping. Mol Ther 2012; 20:580-589.
59. Bostick B, Shin JH, Yue Y, Duan D. AAV-microdystrophin therapy improves cardiac performance in aged female mdx mice. Mol Ther 2011; 19:1826-1832.
60. Schinkel S, Bauer R, Bekeredjian R, et al. Long-term preservation of cardiac structure and function after AAV9-mediated microdystrophin gene transfer in mdx mice. Hum Gene Ther 2012; 23:566-575.
61. Shin JH, Nitahara-Kasahara Y, Hayashita-Kinoh H, et al. Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction. Gene Ther 2011; 18:910-919.
62. Barton-Davis ER, Cordier L, Shoturma DI, et al. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J Clin Invest 1999; 104:375-381. (Pubitemid 29534321)
63. Dunant P, Walter MC, Karpati G, Lochmuller H. Gentamicin fails to increase dystrophin expression in dystrophin-deficient muscle. Muscle Nerve 2003; 27:624-627. (Pubitemid 36523523)
64. Politano L, Nigro G, Nigro V, et al. Gentamicin administration in Duchenne patients with premature stop codon. Preliminary results. Acta Myol 2003; 22:15-21. (Pubitemid 36966404)
65. Malik V, Rodino-Klapac LR, Viollet L, Mendell Jr. Aminoglycosideinduced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy. Ther Adv Neurol Disord 2010; 3:379-389.
66. Welch EM, Barton ER, Zhuo J, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 2007; 447:87-91. (Pubitemid 46685839)
67. Hirawat S, Welch EM, Elfring GL, 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. (Pubitemid 46465953)
68. Finkel RS. Read-through strategies for suppression of nonsense mutations in Duchenne/Becker muscular dystrophy: aminoglycosides and ataluren (PTC124). J Child Neurol 2010; 25:1158-1164.
69. Hoffman EP, Bronson A, Levin AA, et al. Restoring dystrophin expression in Duchenne muscular dystrophy muscle: progress in exon skipping and stop codon read through. Am J Pathol 2011; 179:12-22.
70. Cacchiarelli D, Incitti T, Martone J, et al. miR-31 modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy. EMBO Rep 2011; 12:136-141.
71. Kang JK, Malerba A, Popplewell L, et al. Antisense-induced myostatin exon skipping leads to muscle hypertrophy in mice following octa-guanidine morpholino oligomer treatment. Mol Ther 2011; 19:159-164.
72. Kemaladewi DU, Hoogaars WM, van Heiningen SH, et al. Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy. BMC Med Genomics 2011; 4:36.
73. Zhu J, Li Y, Lu A, et al. Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis. Am J Pathol 2011; 179:915-930.
74. Verhaart IE, Heemskerk H, Karnaoukh TG, et al. Prednisolone treatment does not interfere with 2'-O-methyl phosphorothioate antisense-mediated exon skipping in Duchenne muscular dystrophy. Hum Gene Ther 2012; 23:262-273.
75. Mazzone E, Vasco G, Sormani MP, et al. Functional changes in Duchenne muscular dystrophy: a 12-month longitudinal cohort study. Neurology 2011; 77:250-256.
76. McDonald CM, Henricson EK, Han JJ, et al. The 6-min walk test in Duchenne/Becker muscular dystrophy: longitudinal observations. Muscle Nerve 2010; 42:966-974.
77. McDonald CM, Henricson EK, Han JJ, et al. The 6-min walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle Nerve 2010; 41:500-510.
78. Cacchiarelli D, Legnini I, Martone J, et al. miRNAs as serum biomarkers for Duchenne muscular dystrophy. EMBO Mol Med 2011; 3:258-265.
79. Nadarajah VD, van PM, Chaouch A, et al. Serum matrix metalloproteinase-9 (MMP-9) as a biomarker for monitoring disease progression in Duchenne muscular dystrophy (DMD). Neuromuscul Disord 2011; 21:569-578.
80. Mizuno H, Nakamura A, Aoki Y, et al. Identification of muscle-specific micro-RNAs in serum of muscular dystrophy animal models: promising novel bloodbased markers for muscular dystrophy. PLoS One 2011; 6:e18388.
81. Finanger EL, Russman B, Forbes SC, et al. Use of skeletal muscle MRI in diagnosis and monitoring disease progression in Duchenne muscular dystrophy. Phys Med Rehabil Clin N Am 2012; 23:1-10; ix.
82. Kinali M, Arechavala-Gomeza V, Cirak S, et al. Muscle histology vs. MRI in Duchenne muscular dystrophy. Neurology 2011; 76:346-353.
83. Garrood P, Hollingsworth KG, Eagle M, et al. MR imaging in Duchenne muscular dystrophy: quantification of T1-weighted signal, contrast uptake, and the effects of exercise. J Magn Reson Imaging 2009; 30:1130-1138.