Annals of Clinical Neurophysiology

The Korean Society of Clinical Neurophysiology (대한임상신경생리학회)
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Gene Therapy of Inherited Muscle Diseases

유전성 근육질환의 유전자 치료

  • Shin, Jin-Hong (Department of Neurology, Pusan National University Yangsan Hospital)
  • 신진홍 (양산부산대학교병원 신경과)
  • Received : 2012.12.06
  • Accepted : 2012.12.10
  • Published : 2012.12.30
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Abstract

For the last decades, molecular genetics has achieved great advances that the genes on the list of inherited muscle diseases are piling up. Those diseases of overlapping clinico-pathologic findings are now understood with discrete molecular pathogeneses. We are facing an exciting era that the long-waited gene therapy may eventually come true. Skipping of dystrophin exon 51 is on successful clinical trials, which will benefit about 13% of the children suffering from Duchenne muscular dystrophy. Exon skipping is under active investigation to expand the candidates. Hopefully it may cover majority of Duchenne muscular dystrophy mutations and some of other diseases. Adeno-associated virus is one of the most versatile tools for gene transfer. It may overcome the limitation of exon skipping. Here we review exon skipping technique of Duchenne muscular dystrophy and briefly discuss the other strategies being studied to cure inherited muscle diseases.

Keywords

References

  1. Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987;51:919-928. https://doi.org/10.1016/0092-8674(87)90579-4
  2. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009;461:272-276. https://doi.org/10.1038/nature08250
  3. Sheridan C. Gene therapy finds its niche. Nat Biotech 2011;29:121-128. https://doi.org/10.1038/nbt.1769
  4. Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL, et al. Recombinant human acid ${\alpha}$-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology 2007;68:99-109. https://doi.org/10.1212/01.wnl.0000251268.41188.04
  5. Van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, et al. A randomized study of alglucosidase alfa in late-onset Pompe's disease. N Eng J Med 2010;362:1396-1406. https://doi.org/10.1056/NEJMoa0909859
  6. Meryon E. On granular and fatty degeneration of the voluntary muscles. Med Chir Trans 1852;35:73-84.1.
  7. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010;9:77-93. https://doi.org/10.1016/S1474-4422(09)70271-6
  8. Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL. Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Nat Acad Sci USA 1993;90:3710-3714. https://doi.org/10.1073/pnas.90.8.3710
  9. Aartsma-Rus A, Van Deutekom JCT, Fokkema IF, Van Ommen G-JB, 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;34:135-144. https://doi.org/10.1002/mus.20586
  10. Aartsma-Rus A. Overview on DMD exon skipping. Methods Mol Biol 2012;867:97-116.
  11. Aartsma-Rus A. Overview on AON design. Methods Mol Biol 2012;867:117-129.
  12. Cartegni L, Wang J, Zhu Z, Zhang MQ, Krainer AR. ESEfinder: A web resource to identify exonic splicing enhancers. Nucleic Acids Res 2003;31:3568-3571. https://doi.org/10.1093/nar/gkg616
  13. 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 openlabel, phase 2, dose-escalation study. Lancet 2011;378:595-605. https://doi.org/10.1016/S0140-6736(11)60756-3
  14. 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 Eng J Med 2011;364:1513-1522. https://doi.org/10.1056/NEJMoa1011367
  15. Mendell J, Rodio-Klapac L, Sahenk Z, Roush K, Bird L, Lowes L, et al. Results at 48 weeks of a phase IIb extension study of the exon-skipping drug eteplirsen in patients with Duchenne muscular dystrophy. 17th International Congress of the World Muscle Society. Perth, Australia; 2012.
  16. Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, Van Deutekom J, Van Ommen G-J, et al. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat 2009;30:293-299. https://doi.org/10.1002/humu.20918
  17. 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. https://doi.org/10.1016/j.nmd.2010.03.005
  18. Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord 2002;12:926-929. https://doi.org/10.1016/S0960-8966(02)00140-2
  19. 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. https://doi.org/10.1089/nat.2011.0306
  20. Townsend D, Yasuda S, Li S, Chamberlain JS, Metzger JM. Emergent dilated cardiomyopathy caused by targeted repair of dystrophic skeletal muscle. Mol Ther 2008;16:832-835. https://doi.org/10.1038/mt.2008.52
  21. Moulton HM. In vivo delivery of morpholino oligos by cellpenetrating peptides. Curr Pharm Des 2012;epub.
  22. Shin J-H, Yue Y, Duan D. Recombinant adeno-associated viral vector production and purification. Methods Mol Biol 2012;798:267-284.
  23. Wasala NB, Shin J-H, Duan D. The evolution of heart gene delivery vectors. J Gene Med 2011;13:557-565. https://doi.org/10.1002/jgm.1600
  24. 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:S23-29. https://doi.org/10.1016/S0960-8966(02)00078-0
  25. Liu M, Yue Y, Harper SQ, Grange RW, Chamberlain JS, Duan D. Adeno-associated virus-mediated microdystrophin expression protects young mdx muscle from contraction-induced injury. Mol Ther 2005;11:245-256. https://doi.org/10.1016/j.ymthe.2004.09.013
  26. Gregorevic P, Allen JM, Minami E, Blankinship MJ, Haraguchi M, Meuse L, et al. rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice. Nat Med 2006;12:787-789. https://doi.org/10.1038/nm1439
  27. Shin J-H, Nitahara-Kasahara Y, Hayashita-Kinoh H, Ohshima-Hosoyama S, Kinoshita K, Chiyo T, et al. Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction. Gene Ther 2011;18:910-919. https://doi.org/10.1038/gt.2011.36
  28. Bostick B, Shin J-H, Yue Y, Wasala NB, Lai Y, Duan D. AAV micro-dystrophin gene therapy alleviates stress-induced cardiac death but not myocardial fibrosis in >21-m-old mdx mice, an end-stage model of Duchenne muscular dystrophy cardiomyopathy. J Mol Cell Cardiol 2012;53:217-222. https://doi.org/10.1016/j.yjmcc.2012.05.002
  29. Shin J-H, Yue Y, Srivastava A, Smith B, Lai Y, Duan D. A simplified immune suppression scheme leads to persistent microdystrophin expression in duchenne muscular dystrophy dogs. Hum Gene Ther 2012;23:202-209. https://doi.org/10.1089/hum.2011.147
  30. Bowles DE, McPhee SWJ, 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;20:443-455. https://doi.org/10.1038/mt.2011.237
  31. Vulin A, Barthélémy I, Goyenvalle A, Thibaud J-L, Beley C, Griffith G, et al. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol Ther 2012;20:2120-2133. https://doi.org/10.1038/mt.2012.181
  32. 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. https://doi.org/10.1038/mt.2010.205
  33. Bartel MA, Weinstein JR, Schaffer DV. Directed evolution of novel adeno-associated viruses for therapeutic gene delivery. Gene Ther 2012;19:694-700. https://doi.org/10.1038/gt.2012.20
  34. Aartsma-Rus A, Singh KHK, Fokkema IFAC, Ginjaar IB, Van Ommen G-J, Den Dunnen JT, et al. Therapeutic exon skipping for dysferlinopathies? Eur J Hum Genet 2010;18:889-894. https://doi.org/10.1038/ejhg.2010.4
  35. Grose WE, Clark KR, Griffin D, Malik V, Shontz KM, Montgomery CL, et al. Homologous recombination mediates functional recovery of dysferlin deficiency following AAV5 gene transfer. PLoS One 2012;7:e39233. https://doi.org/10.1371/journal.pone.0039233
  36. 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;287:27629-27636. https://doi.org/10.1074/jbc.M112.391722
  37. Herson S, Hentati F, Rigolet A, Behin A, Romero NB, Leturcq F, et al. A phase I trial of adeno-associated virus serotype 1-${\gamma}$-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C. Brain 2012;135:483-492. https://doi.org/10.1093/brain/awr342
  38. Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, et al. Sustained ${\alpha}$-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol 2010;68:629-638. https://doi.org/10.1002/ana.22251
  39. Buj-Bello A, Fougerousse F, Schwab Y, Messaddeq N, Spehner D, Pierson CR, et al. AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis. Hum Mol Genet 2008;17:2132-2143. https://doi.org/10.1093/hmg/ddn112
  40. Johnson NE, Heatwole CR. Myotonic dystrophy: from bench to bedside. Semin Neurol 2012;32:246-254. https://doi.org/10.1055/s-0032-1329202
  41. 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;488:111-115. https://doi.org/10.1038/nature11362
  42. Chanchlani N. Muscular dystrophy patients could live extra 15 years, if care standards implemented. BMJ 2010;340:c3055. https://doi.org/10.1136/bmj.c3055
  43. Mingozzi F, High KA. Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet 2011;12:341-355.
  44. Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Eng J Med 2008;358:2240-2248. https://doi.org/10.1056/NEJMoa0802315
  45. Flemming A. Regulatory watch: pioneering gene therapy on brink of approval. Nat Rev Drug Discov 2012;11:664.