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Review article: Biomedical intelligence

Vol. 144 No. 0708 (2014)

Molecular targets to treat muscular dystrophies

  • Jochen Kinter
  • Michael Sinnreich
DOI
https://doi.org/10.4414/smw.2014.13916
Cite this as:
Swiss Med Wkly. 2014;144:w13916
Published
09.02.2014

Summary

Muscular dystrophies are classically subdivided according to their clinical phenotype, and were historically defined as progressive myopathies in which muscle biopsies demonstrate muscle fibre necrosis and regeneration, as well as replacement of muscle fibres by adipose and connective tissue. In recent years, great progress has been made in identifying the genetic basis of many myopathies, thereby presenting opportunities to develop therapeutic strategies that act on specific molecular pathomechanisms. The different therapeutic strategies and their molecular targets will be reviewed.

References

  1. Emery AE. Duchenne Muscular Dystrophy. New York: Oxford University Press; 1993.
  2. Emery AE, Skinner R. Clinical studies in benign (Becker type) X-linked muscular dystrophy. Clin Genet. 1976;10(4):189–201. PubMed PMID: 975594.
  3. Nigro G, Comi LI, Politano L, Bain RJ. The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Int J Cardiol. 1990;26(3):271–7. PubMed PMID: 2312196..
  4. Nigro G, Comi LI, Politano L, Limongelli FM, Nigro V, De Rimini ML, et al. Evaluation of the cardiomyopathy in Becker muscular dystrophy. Muscle Nerve. 1995;18(3):283–91. PubMed PMID: 7870105.
  5. Mestroni L, Giacca M. Molecular genetics of dilated cardiomyopathy. Curr Opin Cardiol. 1997;12(3):303–9. PubMed PMID: 9243088.
  6. Grain L, Cortina-Borja M, Forfar C, Hilton-Jones D, Hopkin J, Burch M. Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls. Neuromuscul Disord. 2001;11(2):186–91. PubMed PMID: 11257476.
  7. Mercier S, Toutain A, Toussaint A, Raynaud M, de Barace C, Marcorelles P, et al. Genetic and clinical specificity of 26 symptomatic carriers for dystrophinopathies at pediatric age. Eur J Hum Genet. 2013;21(8):855–63. PubMed PMID: 23299919. Pubmed Central PMCID: PMC3722679.
  8. Viggiano E, Picillo E, Cirillo A, Politano L. Comparison of X-chromosome inactivation in Duchenne muscle/myocardium-manifesting carriers, non-manifesting carriers and related daughters. Clin Genet. 2013;84(3):265–70. PubMed PMID: 23110537.
  9. Soltanzadeh P, Friez MJ, Dunn D, von Niederhausern A, Gurvich OL, Swoboda KJ, et al. Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscul Disord. 2010;20(8):499–504. PubMed PMID: 20630757. Pubmed Central PMCID: PMC2944769.
  10. Nobile C, Marchi J, Nigro V, Roberts RG, Danieli GA. Exon-intron organization of the human dystrophin gene. Genomics. 1997;45(2):421–4. PubMed PMID: 9344670.
  11. Hoffman EP, Brown RH, Jr., Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987;51(6):919–28. PubMed PMID: 3319190.
  12. Culligan KG, Mackey AJ, Finn DM, Maguire PB, Ohlendieck K. Role of dystrophin isoforms and associated proteins in muscular dystrophy (review). Int J Mol Med. 1998;2(6):639–48. PubMed PMID: 9850730.
  13. Ervasti JM, Campbell KP. Membrane organization of the dystrophin-glycoprotein complex. Cell. 1991;66(6):1121–31. PubMed PMID: 1913804.
  14. Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT. Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve. 2006;34(2):135–44. PubMed PMID: 16770791.
  15. Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2008(1). PubMed PMID: WOS:000252926800138.
  16. Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2004(2):CD003725. PubMed PMID: 15106215.
  17. Moxley RT, 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, et al. Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2005;64(1):13–20. PubMed PMID: 15642897.
  18. Ricotti V, Ridout DA, Scott E, Quinlivan R, Robb SA, Manzur AY, et al. Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry. 2013;84(6):698–705. PubMed PMID: 23250964.
  19. Partridge TA, Grounds M, Sloper JC. Evidence of fusion between host and donor myoblasts in skeletal muscle grafts. Nature. 1978;273(5660):306–8. PubMed PMID: 652035.
  20. Law PK, Yap JL. New muscle transplant method produces normal twitch tension in dystrophic muscle. Muscle Nerve. 1979;2(5):356–63. PubMed PMID: 492212.
  21. Skuk D, Goulet M, Roy B, Chapdelaine P, Bouchard JP, Roy R, et al. Dystrophin expression in muscles of duchenne muscular dystrophy patients after high-density injections of normal myogenic cells. J Neuropathol Exp Neurol. 2006;65(4):371–86. PubMed PMID: 16691118.
  22. Skuk D, Goulet M, Roy B, Piette V, Côté CH, Chapdelaine P, et al. First test of a “high-density injection” protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: eighteen months follow-up. Neuromuscul Disord. 2007;17(1):38–46. PubMed PMID: 17142039.
  23. Wein N, Avril A, Bartoli M, Beley C, Chaouch S, Laforêt P, et al. Efficient bypass of mutations in dysferlin deficient patient cells by antisense-induced exon skipping. Hum Mutat. 2010;31(2):136–42. PubMed PMID: 19953532.
  24. Skuk D, Paradis M, Goulet M, Tremblay JP. Ischemic central necrosis in pockets of transplanted myoblasts in nonhuman primates: implications for cell-transplantation strategies. Transplantation. 2007;84(10):1307–15. PubMed PMID: 18049116.
  25. Torrente Y, Belicchi M, Marchesi C, D'Antona G, Cogiamanian F, Pisati F, et al. Autologous transplantation of muscle-derived CD133(+) stem cells in Duchenne muscle patients. Cell Transplant. 2007;16(6):563–77. PubMed PMID: WOS:000249513200001.
  26. Moisset PA, Skuk D, Asselin I, Goulet M, Roy B, Karpati G, et al. Successful transplantation of genetically corrected DMD myoblasts following ex vivo transduction with the dystrophin minigene. Biochem Biophys Res Commun. 1998;247(1):94–9. PubMed PMID: 9636661.
  27. Moisset PA, Gagnon Y, Karpati G, Tremblay JP. Expression of human dystrophin following the transplantation of genetically modified mdx myoblasts. Gene Ther. 1998;5(10):1340–6. PubMed PMID: 9930339.
  28. Ikemoto M, Fukada S, Uezumi A, Masuda S, Miyoshi H, Yamamoto H, et al. Autologous transplantation of SM/C-2.6(+) satellite cells transduced with micro-dystrophin CS1 cDNA by lentiviral vector into mdx mice. Mol Ther. 2007;15(12):2178–85. PubMed PMID: 17726457.
  29. Tedesco FS, Dellavalle A, Diaz-Manera J, Messina G, Cossu G. Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells. J Clin Invest. 2010;120(1):11–9. PubMed PMID: 20051632. Pubmed Central PMCID: PMC2798695..
  30. Kazuki Y, Hiratsuka M, Takiguchi M, Osaki M, Kajitani N, Hoshiya H, et al. Complete genetic correction of ips cells from Duchenne muscular dystrophy. Mol Ther. 2010;18(2):386–93. PubMed PMID: 19997091. Pubmed Central PMCID: PMC2839293..
  31. Goudenege S, Lebel C, Huot NB, Dufour C, Fujii I, Gekas J, et al. Myoblasts derived from normal hESCs and dystrophic hiPSCs efficiently fuse with existing muscle fibers following transplantation. Mol Ther. 2012;20(11):2153–67. PubMed PMID: 22990676. Pubmed Central PMCID: PMC3498803..
  32. Karpati G, Carpenter S, Morris GE, Davies KE, Guerin C, Holland P. Localization and quantitation of the chromosome 6-encoded dystrophin-related protein in normal and pathological human muscle. J Neuropathol Exp Neurol. 1993;52(2):119–28. PubMed PMID: 8440993.
  33. Gussoni E, Pavlath GK, Lanctot AM, Sharma KR, Miller RG, Steinman L, et al. Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation. Nature. 1992;356(6368):435–8. PubMed PMID: 1557125.
  34. Mendell JR, Kissel JT, Amato AA, King W, Signore L, Prior TW, et al. Myoblast transfer in the treatment of Duchenne’s muscular dystrophy. N Engl J Med. 1995;333(13):832–8. PubMed PMID: 7651473.
  35. Torrente Y, Belicchi M, Sampaolesi M, Pisati F, Meregalli M, D’Antona G, et al. Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. J Clin Invest. 2004;114(2):182–95. PubMed PMID: 15254585. Pubmed Central PMCID: PMC449743.
  36. Sampaolesi M, Torrente Y, Innocenzi A, Tonlorenzi R, D'Antona G, Pellegrino MA, et al. Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science. 2003;301(5632):487–92. PubMed PMID: WOS:000184340500034.
  37. Sampaolesi M, Blot S, D’Antona G, Granger N, Tonlorenzi R, Innocenzi A, et al. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature. 2006;444(7119):574–9. PubMed PMID: 17108972.
  38. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, et al. Direct gene transfer into mouse muscle in vivo. Science. 1990;247(4949 Pt 1):1465–8. PubMed PMID: 1690918.
  39. DelloRusso C, Scott JM, Hartigan-O’Connor D, Salvatori G, Barjot C, Robinson AS, et al. Functional correction of adult mdx mouse muscle using gutted adenoviral vectors expressing full-length dystrophin. Proc Natl Acad Sci U S A. 2002;99(20):12979–84. PubMed PMID: 12271128.
  40. Watchko J, O’Day T, Wang B, Zhou L, Tang Y, Li J, et al. Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther. 2002;13(12):1451–60. PubMed PMID: 12215266.
  41. Wolff JA, Ludtke JJ, Acsadi G, Williams P, Jani A. Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet. 1992;1(6):363–9. PubMed PMID: 1301910.
  42. Acsadi G, Dickson G, Love DR, Jani A, Walsh FS, Gurusinghe A, et al. Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs. Nature. 1991;352(6338):815–8. PubMed PMID: 1881437.
  43. Liu F, Nishikawa M, Clemens PR, Huang L. Transfer of full-length Dmd to the diaphragm muscle of Dmd(mdx/mdx) mice through systemic administration of plasmid DNA. Mol Ther. 2001;4(1):45–51. PubMed PMID: 11472105.
  44. Liang KW, Nishikawa M, Liu F, Sun B, Ye Q, Huang L. Restoration of dystrophin expression in mdx mice by intravascular injection of naked DNA containing full-length dystrophin cDNA. Gene Ther. 2004;11(11):901–8. PubMed PMID: 14985786.
  45. Zhang G, Ludtke JJ, Thioudellet C, Kleinpeter P, Antoniou M, Herweijer H, et al. Intraarterial delivery of naked plasmid DNA expressing full-length mouse dystrophin in the mdx mouse model of duchenne muscular dystrophy. Hum Gene Ther. 2004;15(8):770–82. PubMed PMID: 15319034.
  46. Romero NB, Braun S, Benveniste O, Leturcq F, Hogrel JY, Morris GE, et al. Phase I study of dystrophin plasmid-based gene therapy in Duchenne/Becker muscular dystrophy. Hum Gene Ther. 2004;15(11):1065–76. PubMed PMID: 15610607.
  47. Li S, Kimura E, Fall BM, Reyes M, Angello JC, Welikson R, et al. Stable transduction of myogenic cells with lentiviral vectors expressing a minidystrophin. Gene Ther. 2005;12(14):1099–108. PubMed PMID: WOS:000230323100002.
  48. Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348(3):255–6. PubMed PMID: WOS:000180390600013.
  49. Yi Y, Hahm SH, Lee KH. Retroviral gene therapy: safety issues and possible solutions. Curr Gene Ther. 2005;5(1):25–35. PubMed PMID: 15638709.
  50. Bachrach E, Perez AL, Choi YH, Illigens BMW, Jun SJ, Del Nido P, et al. Muscle engraftment of myogenic progenitor cells following intraarterial transplantation. Muscle Nerve. 2006;34(1):44–52. PubMed PMID: WOS:000238688000004.
  51. Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L, et al. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nature Cell Biol. 2007;9(3):255–U30. PubMed PMID: WOS:000244558600010.
  52. Acsadi G, Lochmuller H, Jani A, Huard J, Massie B, Prescott S, et al. Dystrophin expression in muscles of mdx mice after adenovirus-mediated in vivo gene transfer. Hum Gene Ther. 1996;7(2):129–40. PubMed PMID: WOS:A1996UG13500001.
  53. Vincent N, Ragot T, Gilgenkrantz H, Couton D, Chafey P, Gregoire A, et al. Long-term correction of mouse dystrophic degeneration by adenovirus-mediated transfer of a minidystrophin gene. Nature Genet. 1993;5(2):130–4. PubMed PMID: WOS:A1993MA05600009.
  54. Clemens PR, Kochanek S, Sunada Y, Chan S, Chen HH, Campbell KP, et al. In vivo muscle gene transfer of full-length dystrophin with an adenoviral vector that lacks all viral genes. Gene Ther. 1996;3(11):965–72. PubMed PMID: WOS:A1996VR64300004.
  55. Gilbert R, Dudley RW, Liu AB, Petrof BJ, Nalbantoglu J, Karpati G. Prolonged dystrophin expression and functional correction of mdx mouse muscle following gene transfer with a helper-dependent (gutted) adenovirus-encoding murine dystrophin. Hum Mol Genet. 2003;12(11):1287–99. PubMed PMID: 12761044.
  56. Dudley RW, Lu Y, Gilbert R, Matecki S, Nalbantoglu J, Petrof BJ, et al. Sustained improvement of muscle function one year after full-length dystrophin gene transfer into mdx mice by a gutted helper-dependent adenoviral vector. Hum Gene Ther. 2004;15(2):145–56. PubMed PMID: 14975187.
  57. Scott JM, Li S, Harper SQ, Welikson R, Bourque D, DelloRusso C, et al. Viral vectors for gene transfer of micro-, mini-, or full-length dystrophin. Neuromuscul Disord. 2002;12(Suppl 1):S23–9. PubMed PMID: 12206791.
  58. Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000;97(25):13714–9. PubMed PMID: 11095710.
  59. Gregorevic P, Blankinship MJ, Allen JM, Crawford RW, Meuse L, Miller DG, et al. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med. 2004;10(8):828–34. PubMed PMID: 15273747.
  60. Herzog RW, Yang EY, Couto LB, Hagstrom JN, Elwell D, Fields PA, et al. Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector. Nat Med. 1999;5(1):56–63. PubMed PMID: WOS:000077885000030.
  61. Manno CS, Chew AJ, Hutchison S, Larson PJ, Herzog RW, Arruda VP, et al. AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood. 2003;101(8):2963–72. PubMed PMID: WOS:000182101400015.
  62. Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, et al. Dystrophin immunity in Duchenne’s muscular dystrophy. N Engl J Med. 2010;363(15):1429–37. PubMed PMID: 20925545. Pubmed Central PMCID: PMC3014106.
  63. Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ, Camp AS, et al. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther. 2012;20(2):443–55. PubMed PMID: 22068425. Pubmed Central PMCID: PMC3277234.
  64. Barton-Davis ER, Cordier L, Shoturma DI, Leland SE, Sweeney HL. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J Clin Invest. 1999;104(4):375–81. PubMed PMID: 10449429.
  65. Dunant P, Walter MC, Karpati G, Lochmuller H. Gentamicin fails to increase dystrophin expression in dystrophin-deficient muscle. Muscle Nerve. 2003;27(5):624–7. PubMed PMID: 12707984.
  66. Wagner KR, Hamed S, Hadley DW, Gropman AL, Burstein AH, Escolar DM, et al. Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations. Ann Neurol. 2001;49(6):706–11. PubMed PMID: 11409421.
  67. Serrano C WC, Moore. Gentamicin treatment for muscular dystrophy with stop codon mutations. Neurology. 2001;56(Suppl 3): A79.
  68. Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W, Al-Dahhak R, et al. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann Neurol. 2010;67(6):771–80. PubMed PMID: 20517938.
  69. Aurino S, Nigro V. Readthrough strategies for stop codons in Duchenne muscular dystrophy. Acta Myol. 2006;25(1):5–12. PubMed PMID: 17039975.
  70. Finkel RS. Read-through strategies for suppression of nonsense mutations in Duchenne/ Becker muscular dystrophy: aminoglycosides and ataluren (PTC124). J Child Neurol. 2010;25(9):1158–64. PubMed PMID: 20519671.
  71. Hoffman EP, Bronson A, Levin AA, Takeda S, Yokota T, Baudy AR, et al. Restoring dystrophin expression in duchenne muscular dystrophy muscle progress in exon skipping and stop codon read through. Am J Pathol. 2011;179(1):12-22. PubMed PMID: 21703390. Pubmed Central PMCID: PMC3124804.
  72. Dunckley MG, Manoharan M, Villiet P, Eperon IC, Dickson G. Modification of splicing in the dystrophin gene in cultured Mdx muscle cells by antisense oligoribonucleotides. Hum Mol Genet. 1998;7(7):1083–90. PubMed PMID: 9618164.
  73. Lu QL, Rabinowitz A, Chen YC, Yokota T, Yin H, Alter J, et al. Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc Natl Acad Sci U S A. 2005;102(1):198–203. PubMed PMID: 15608067.
  74. McClorey G, Moulton HM, Iversen PL, Fletcher S, Wilton SD. Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD. Gene Ther. 2006;13(19):1373–81. PubMed PMID: 16724091.
  75. Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, 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(9791):595–605. PubMed PMID: 21784508. Pubmed Central PMCID: PMC3156980.
  76. Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF, Heuvelmans N, et al. Systemic Administration of PRO051 in Duchenne's Muscular Dystrophy. N Engl J Med. 2011;364(16):1513–22. PubMed PMID: WOS:000289722700008.
  77. Opar A. Exon-skipping drug pulls ahead in muscular dystrophy field. Nat Med. 2012;18(9):1314. PubMed PMID: 22961147.
  78. Ohlendieck K, Ervasti JM, Matsumura K, Kahl SD, Leveille CJ, Campbell KP. Dystrophin-related protein is localized to neuromuscular junctions of adult skeletal muscle. Neuron. 1991;7(3):499–508. PubMed PMID: 1654951.
  79. Khurana TS, Watkins SC, Chafey P, Chelly J, Tome FM, Fardeau M, et al. Immunolocalization and developmental expression of dystrophin related protein in skeletal muscle. Neuromuscul Disord. 1991;1(3):185–94. PubMed PMID: 1822793.
  80. Matsumura K, Ervasti JM, Ohlendieck K, Kahl SD, Campbell KP. Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. Nature. 1992;360(6404):588–91. PubMed PMID: 1461282.
  81. Tinsley JM, Blake DJ, Roche A, Fairbrother U, Riss J, Byth BC, et al. Primary structure of dystrophin-related protein. Nature. 1992;360(6404):591–3. PubMed PMID: 1461283.
  82. Tinsley J, Deconinck N, Fisher R, Kahn D, Phelps S, Gillis JM, et al. Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat Med. 1998;4(12):1441–4. PubMed PMID: 9846586.
  83. Moorwood C, Lozynska O, Suri N, Napper AD, Diamond SL, Khurana TS. Drug discovery for Duchenne muscular dystrophy via utrophin promoter activation screening. PLoS One. 2011;6(10):e26169. PubMed PMID: 22028826. Pubmed Central PMCID: PMC3197614.
  84. Tinsley JM, Fairclough RJ, Storer R, Wilkes FJ, Potter AC, Squire SE, 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(5). PubMed PMID: WOS:000290305600014.
  85. Krag TO, Bogdanovich S, Jensen CJ, Fischer MD, Hansen-Schwartz J, Javazon EH, et al. Heregulin ameliorates the dystrophic phenotype in mdx mice. Proc Natl Acad Sci U S A. 2004;101(38):13856–60. PubMed PMID: 15365169. Pubmed Central PMCID: PMC518764.
  86. Gilbert R, Nalbanoglu J, Tinsley JM, Massie B, Davies KE, Karpati G. Efficient utrophin expression following adenovirus gene transfer in dystrophic muscle. Biochem Biophys Res Commun. 1998;242(1):244–7. PubMed PMID: 9439643.
  87. Cerletti M, Negri T, Cozzi F, Colpo R, Andreetta F, Croci D, et al. Dystrophic phenotype of canine X-linked muscular dystrophy is mitigated by adenovirus-mediated utrophin gene transfer. Gene Ther. 2003;10(9):750–7. PubMed PMID: 12704413.
  88. Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, et al. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet. 1998;20(1):37–42. PubMed PMID: 9731527.
  89. Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, et al. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998;20(1):31–6. PubMed PMID: 9731526.
  90. Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, et al. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature. 2003;423(6936):168–72. PubMed PMID: 12736685.
  91. Han R, Campbell KP. Dysferlin and muscle membrane repair. Curr Opin Cell Biol. 2007;19(4):409–16. PubMed PMID: 17662592. Pubmed Central PMCID: PMC2144911.
  92. Weiler T, Bashir R, Anderson LV, Davison K, Moss JA, Britton S, et al. Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s). Hum Mol Genet. 1999;8(5):871–7. PubMed PMID: 10196377.
  93. Illarioshkin SN, Ivanova-Smolenskaya IA, Greenberg CR, Nylen E, Sukhorukov VS, Poleshchuk VV, et al. Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and distal myopathy. Neurology. 2000;55(12):1931–3. PubMed PMID: 11134403.
  94. Wenzel K, Geier C, Qadri F, Hubner N, Schulz H, Erdmann B, et al. Dysfunction of dysferlin-deficient hearts. J Mol Med (Berl). 2007;85(11):1203–14. PubMed PMID: 17828519.
  95. Sinnreich M, Therrien C, Karpati G. Lariat branch point mutation in the dysferlin gene with mild limb-girdle muscular dystrophy. Neurology. 2006;66(7):1114–6. PubMed PMID: 16606933.
  96. Aartsma-Rus A, Singh KH, Fokkema IF, Ginjaar IB, van Ommen GJ, den Dunnen JT, et al. Therapeutic exon skipping for dysferlinopathies? Eur J Hum Genet. 2010;18(8):889–94. PubMed PMID: 20145676. Pubmed Central PMCID: PMC2987387.
  97. Wang B, Yang Z, Brisson BK, Feng H, Zhang Z, Welch EM, et al. Membrane blebbing as an assessment of functional rescue of dysferlin-deficient human myotubes via nonsense suppression. J Appl Physiol. 2010;109(3):901–5. PubMed PMID: 20558759.
  98. Krahn M, Wein N, Bartoli M, Lostal W, Courrier S, Bourg-Alibert N, et al. A naturally occurring human minidysferlin protein repairs sarcolemmal lesions in a mouse model of dysferlinopathy. Sci Transl Med. 2010;2(50):50ra69. PubMed PMID: 20861509.
  99. Azakir BA, Di Fulvio S, Salomon S, Brockhoff M, Therrien C, Sinnreich M. Modular dispensability of dysferlin C2 domains reveals rational design for mini-dysferlin molecules. J Biol Chem. 2012;287(33):27629–36. PubMed PMID: 22736764. Pubmed Central PMCID: PMC3431656.
  100. Azakir BA, Di Fulvio S, Kinter J, Sinnreich M. Proteasomal inhibition restores biological function of mis-sense mutated dysferlin in patient-derived muscle cells. J Biol Chem. 2012;287(13):10344–54. PubMed PMID: 22318734. Pubmed Central PMCID: PMC3323038.
  101. Schoewel V, Marg A, Kunz S, Overkamp T, Carrazedo RS, Zacharias U, et al. Dysferlin-peptides reallocate mutated dysferlin thereby restoring function. PLoS One. 2012;7(11):e49603. PubMed PMID: 23185377. Pubmed Central PMCID: PMC3502493.
  102. Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992;68(4):799–808. PubMed PMID: 1310900.
  103. Liquori CL, Ricker K, Moseley ML, Jacobsen JF, Kress W, Naylor SL, et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science. 2001;293(5531):864–7. PubMed PMID: 11486088.
  104. de Die-Smulders CE, Howeler CJ, Thijs C, Mirandolle JF, Anten HB, Smeets HJ, et al. Age and causes of death in adult-onset myotonic dystrophy. Brain. 1998;121(Pt 8):1557–63. PubMed PMID: 9712016.
  105. Harper PS. Congenital myotonic dystrophy in Britain. I. Clinical aspects. Arch Dis Child. 1975;50(7):505-13. PubMed PMID: 1101835.
  106. Reardon W, Harley HG, Brook JD, Rundle SA, Crow S, Harper PS, et al. Minimal expression of myotonic dystrophy: a clinical and molecular analysis. J Med Genet. 1992;29(11):770–3. PubMed PMID: 1453424.
  107. MacDonald JR, Hill JD, Tarnopolsky MA. Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy. Neurology. 2002;59(12):1876–80. PubMed PMID: 12499477.
  108. Damian MS, Gerlach A, Schmidt F, Lehmann E, Reichmann H. Modafinil for excessive daytime sleepiness in myotonic dystrophy. Neurology. 2001;56(6):794–6. PubMed PMID: 11274321.
  109. Brunner HG, Bruggenwirth HT, Nillesen W, Jansen G, Hamel BC, Hoppe RL, et al. Influence of sex of the transmitting parent as well as of parental allele size on the CTG expansion in myotonic dystrophy (DM). Am J Hum Genet. 1993;53(5):1016–23. PubMed PMID: 8213829.
  110. Jansen G, Willems P, Coerwinkel M, Nillesen W, Smeets H, Vits L, et al. Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n repeat variation and selection against extreme expansion in sperm. Am J Hum Genet. 1994;54(4):575–85. PubMed PMID: 8128954.
  111. Kovtun IV, McMurray CT. Trinucleotide expansion in haploid germ cells by gap repair. Nat Genet. 2001;27(4):407–11. PubMed PMID: 11279522.
  112. Fu YH, Friedman DL, Richards S, Pearlman JA, Gibbs RA, Pizzuti A, et al. Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy. Science. 1993;260(5105):235–8. PubMed PMID: 8469976.
  113. Reddy S, Smith DB, Rich MM, Leferovich JM, Reilly P, Davis BM, et al. Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy. Nat Genet. 1996;13(3):325–35. PubMed PMID: 8673132.
  114. Jansen G, Groenen PJ, Bachner D, Jap PH, Coerwinkel M, Oerlemans F, et al. Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice. Nat Genet. 1996;13(3):316–24. PubMed PMID: 8673131.
  115. Mankodi A, Logigian E, Callahan L, McClain C, White R, Henderson D, et al. Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science. 2000;289(5485):1769–73. PubMed PMID: 10976074.
  116. Michalowski S, Miller JW, Urbinati CR, Paliouras M, Swanson MS, Griffith J. Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein. Nucleic Acids Res. 1999;27(17):3534–42. PubMed PMID: 10446244.
  117. Mooers BH, Logue JS, Berglund JA. The structural basis of myotonic dystrophy from the crystal structure of CUG repeats. Proc Natl Acad Sci U S A. 2005;102(46):16626–31. PubMed PMID: 16269545.
  118. Kino Y, Mori D, Oma Y, Takeshita Y, Sasagawa N, Ishiura S. Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats. Hum Mol Genet. 2004;13(5):495–507. PubMed PMID: 14722159.
  119. Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA, et al. Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. Embo J. 2000;19(17):4439–48. PubMed PMID: 10970838.
  120. Faustino NA, Cooper TA. Pre-mRNA splicing and human disease. Genes Dev. 2003;17(4):419–37. PubMed PMID: 12600935.
  121. Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D, et al. A muscleblind knockout model for myotonic dystrophy. Science. 2003;302(5652):1978–80. PubMed PMID: 14671308.
  122. Kuyumcu-Martinez NM, Wang GS, Cooper TA. Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation. Mol Cell. 2007;28(1):68–78. PubMed PMID: 17936705. Pubmed Central PMCID: PMC2083558.
  123. Ho TH, Bundman D, Armstrong DL, Cooper TA. Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy. Hum Mol Genet. 2005;14(11):1539–47. PubMed PMID: 15843400.
  124. Mulders S, van den Broek W, Wheeler T, Croes H, van Kuik-Romeijn P, de Kimpe S, et al. Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy. Proc Natl Acad Sci U S A. 2009;106(33):13915-20. PubMed PMID: 19667189. Pubmed Central PMCID: PMC2728995.
  125. Wheeler T, Sobczak K, Lueck J, Osborne R, Lin X, Dirksen R, et al. Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA. Science. 2009;325(5938):336–9. PubMed PMID: 19608921.
  126. Lee JE, Bennett CF, Cooper TA. RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1. Proc Natl Acad Sci U S A. 2012;109(11):4221–6. PubMed PMID: 22371589. Pubmed Central PMCID: PMC3306674.
  127. Wheeler TM, Leger AJ, Pandey SK, MacLeod AR, Nakamori M, Cheng SH, et al. Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature. 2012;488(7409):111–5. PubMed PMID: 22859208.
  128. Furling D, Doucet G, Langlois MA, Timchenko L, Belanger E, Cossette L, et al. Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions. Gene Ther. 2003;10(9):795–802. PubMed PMID: 12704419.
  129. Langlois MA, Boniface C, Wang G, Alluin J, Salvaterra PM, Puymirat J, et al. Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in myotonic dystrophy cells. J Biol Chem. 2005;280(17):16949–54. PubMed PMID: 15722335.
  130. Langlois MA, Lee NS, Rossi JJ, Puymirat J. Hammerhead ribozyme-mediated destruction of nuclear foci in myotonic dystrophy myoblasts. Mol Ther. 2003;7(5 Pt 1):670-80. PubMed PMID: 12718910.
  131. García-López A, Llamusí B, Orzáez M, Pérez-Payá E, Artero RD. In vivo discovery of a peptide that prevents CUG-RNA hairpin formation and reverses RNA toxicity in myotonic dystrophy models. Proc Natl Acad Sci U S A. 2011;108(29):11866–71. PubMed PMID: 21730182. Pubmed Central PMCID: PMC3141925.
  132. Pushechnikov A, Lee M, Childs-Disney J, Sobczak K, French J, Thornton C, et al. Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3. J Am Chem Soc. 2009;131(28):9767–79. PubMed PMID: 19552411. Pubmed Central PMCID: PMC2731475.
  133. Childs-Disney JL, Hoskins J, Rzuczek SG, Thornton CA, Disney MD. Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive. ACS Chem Biol. 2012;7(5):856–62. PubMed PMID: 22332923. Pubmed Central PMCID: PMC3356481.
  134. Warf M, Nakamori M, Matthys C, Thornton C, Berglund J. Pentamidine reverses the splicing defects associated with myotonic dystrophy. Proc Natl Acad Sci U S A. 2009;106(44):18551–6. PubMed PMID: 19822739. Pubmed Central PMCID: PMC2774031.
  135. Lunt PW, Harper PS. Genetic counselling in facioscapulohumeral muscular dystrophy. J Med Genet. 1991;28(10):655–64. PubMed PMID: 1941962.
  136. Jardine PE, Koch MC, Lunt PW, Maynard J, Bathke KD, Harper PS, et al. De novo facioscapulohumeral muscular dystrophy defined by DNA probe p13E-11 (D4F104S1). Arch Dis Child. 1994;71(3):221–7. PubMed PMID: 7979495.
  137. Wohlgemuth M, van der Kooi EL, van Kesteren RG, van der Maarel SM, Padberg GW. Ventilatory support in facioscapulohumeral muscular dystrophy. Neurology. 2004;63(1):176–8. PubMed PMID: 15249635.
  138. Wohlgemuth M, de Swart BJ, Kalf JG, Joosten FB, Van der Vliet AM, Padberg GW. Dysphagia in facioscapulohumeral muscular dystrophy. Neurology. 2006;66(12):1926–8. PubMed PMID: 16801662.
  139. Fitzsimons RB, Gurwin EB, Bird AC. Retinal vascular abnormalities in facioscapulohumeral muscular dystrophy. A general association with genetic and therapeutic implications. Brain. 1987;110 ( Pt 3):631–48. PubMed PMID: 3580827.
  140. Padberg GW, Frants RR, Brouwer OF, Wijmenga C, Bakker E, Sandkuijl LA. Facioscapulohumeral muscular dystrophy in the Dutch population. Muscle Nerve. 1995;2:S81–4. PubMed PMID: 7739631.
  141. Wijmenga C, Padberg GW, Moerer P, Wiegant J, Liem L, Brouwer OF, et al. Mapping of facioscapulohumeral muscular dystrophy gene to chromosome 4q35-qter by multipoint linkage analysis and in situ hybridization. Genomics. 1991;9(4):570–5. PubMed PMID: 2037288.
  142. van Deutekom JC, Wijmenga C, van Tienhoven EA, Gruter AM, Hewitt JE, Padberg GW, et al. FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet. 1993;2(12):2037–42. PubMed PMID: 8111371.
  143. van Geel M, Dickson MC, Beck AF, Bolland DJ, Frants RR, van der Maarel SM, et al. Genomic analysis of human chromosome 10q and 4q telomeres suggests a common origin. Genomics. 2002;79(2):210–7. PubMed PMID: 11829491.
  144. Lemmers RJ, de Kievit P, Sandkuijl L, Padberg GW, van Ommen GJ, Frants RR, et al. Facioscapulohumeral muscular dystrophy is uniquely associated with one of the two variants of the 4q subtelomere. Nat Genet. 2002;32(2):235–6. PubMed PMID: 12355084.