Moving towards successful exon-skipping therapy for Duchenne muscular dystrophy


Duchenne muscular dystrophy (DMD) is an X chromosome-linked lethal muscular disorder with progressing muscle wasting and weakness caused by mutations in the gene encoding a subsarcolemmal protein dystrophin. For a long time, there was no effective cure; however, advances in molecular biology have allowed the development of radical treatment approaches. Among them, exon-skipping therapy using antisense oligonucleotides is very promising, because it corrects the reading frame of the dystrophin-encoding gene and restores protein expression, resulting in the conversion of DMD to a clinically milder form, Becker muscular dystrophy (BMD). However, clinical trials in exon-skipping therapy did not provide satisfactory results, which may be attributed to inefficient exon skipping, low expression level of restored dystrophin and inadequate methods of muscle function evaluation. To date, exon-skipping approaches have particularly focused on the correction of the gene-reading frame. However, the problem is that the relationship between the resultant and expected phenotypes in terms of definite symptomatic improvement has not yet been elucidated. In other words, previously conducted clinical trials have not been planned based on the comprehensive assessment of genotype–phenotype relationship in BMD, which demonstrates a broad range of symptom severity depending on the functional activity of the truncated dystrophin. The analysis I present in this review strongly suggests that the development of exon-skipping therapy and its clinical trials should be based on large-cohort studies of BMD.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2


  1. 1

    Hoffman, E. P., Brown, R. H. & Kunkel, L. M. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51, 919–928 (1987).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2

    Sunada, Y. & Campbell, K. P. Dystrophin-glycoprotein complex: molecular organization and critical roles in skeletal muscle. Curr. Opin. Neurol. 8, 379–384 (1995).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3

    Yeung, E. W., Whitehead, N. P., Suchyna, T. M., Gottieb, P. A., Sachs, F. & Allen, D. D. Effects of stretch-activated channel blockers on [Ca2+]i and muscle damage in the mdx mouse. J. Physiol. 562, 367–380 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Porter, J. D., Khanna, S., Kaminski, H. J., Rao, J. S., Merriam, A. P., Richmonds, C. R. et al. A chronic inflammatory response dominates the skeletal muscle molecular signature in dystrophin-deficient mdx mice. Hum. Mol. Genet. 11, 263–272 (2002).

    CAS  Article  Google Scholar 

  5. 5

    Monaco, A. P., Bertelson, C. J., Liechti-Gallati, S., Moser, H. & Kunkel, L. M. An explanation for the phenotype differences between patients bearing partial deletions of the DMD locus. Genomics 2, 90–95 (1998).

    Article  Google Scholar 

  6. 6

    Koenig, M., Beggs, A. H., Moyer, M., Scherpf, S., Heindrich, K. & Bettecken, T. el al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am. J. Hum. Genet. 45, 498–506 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Tuffery-Giraud, S., Beroud, C., Leturcq, F., Yaou, R. B., Hamroun, D., Michel-Calemard, L. et al. Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using UMD-DMD database: a model of nationwide knowledgebase. Hum. Mutat. 30, 934–945 (2009).

    CAS  Article  Google Scholar 

  8. 8

    Bushby, K., Finkel, R., Birnkrant, D. J., Case, L. E., Clemens, P. R., Cripe, L. et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9, 77–93 (2010).

    Article  Google Scholar 

  9. 9

    Yokota, T., Pistilli, E., Duddy, W. & Nagaraju, K. Potential of oligonucleotide-mediated exon-skipping therapy for Duchenne muscular dystrophy. Expert. Opin. Biol. Ther. 7, 831–842 (2007).

    CAS  Article  Google Scholar 

  10. 10

    Okada, T. & Takeda, S. Current challenges and future directions in recombinant AAV-mediated gene therapy of Duchenne muscular dystrophy. Pharmaceuticals (Basel) 6, 813–836 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11

    Welch, E. M., Barton, E. R., Zhuo, J., Tomizawa, Y., Friesen, W. J., Trifillis, P. et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 447, 87–92 (2007).

    CAS  Article  Google Scholar 

  12. 12

    Bajek, A., Porowinska, D., Kloskowski, T., Brzoska, E., Ciemerych, M. A. & Drewa, T. Cell therapy in Duchenne muscular dystrophy treatment: clinical trials overview. Crit. Rev. Eukaryot. Gene Expr. 25, 1–11 (2015).

    Article  Google Scholar 

  13. 13

    Houang, E. M., Haman, K. J., Filareto, A., Perlingeiro, R. C., Bates, F. S., Lowe, D. A. et al. Membrane-stabilizing copolymers confer marked protection to dystrophic skeletal muscle in vivo. Mol. Ther. Methods Clin. Dev. 2, 15042 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Iwata, Y., Katanosaka, Y., Arai, Y., Shigekawa, M. & Wakabayashi, S. Dominant-negative inhibition of Ca2+ influx via TRPV2 ameliorates muscular dystrophy in animal models. Hum. Mol. Genet. 18, 824–834 (2009).

    CAS  Article  Google Scholar 

  15. 15

    Ermolova, N. V., Martinez, L., Vetrone, S. A., Jordan, M. C., Roos, K. P., Sweeney, H. L. et al. Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function. Neuromuscul. Disord. 24, 583–595 (2014).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16

    Childers, M. K., Bogan, J. R., Bogan, D. J., Greiner, H., Holder, M., Grange, R. W. et al. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of duchenne muscular dystrophy. Front. Pharmacol. 2, 89 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17

    Morales, M. G., Cabrera, D., Céspedes, C., Vio, C. P., Vazquez, Y., Brandan, E. et al. Inhibition of the angiotensin-converting enzyme decreases skeletal muscle fibrosis in dystrophic mice by a diminution in the expression and activity of connective tissue growth factor (CTGF/CCN-2). Cell Tissue Res. 353, 173–187 (2013).

    CAS  Article  Google Scholar 

  18. 18

    Apolinário, L. M., De Carvalho, S. C., Santo Neto, H. & Marques, M. J. Long-term therapy with omega-3 ameliorates myonecrosis and benefits skeletal muscle regeneration in Mdx mice. Anat. Rec. (Hoboken) 298, 1589–1596 (2015).

    Article  Google Scholar 

  19. 19

    Hayashiji, N., Yuasa, S., Miyagoe-Suzuki, Y., Hara, M., Ito, N., Hashimoto, H. et al. G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy. Nat. Commun. 6, 6745 (2015).

    CAS  Article  Google Scholar 

  20. 20

    Ricotti, V., Spinty, S., Roper, H., Hughes, I., Tejuram, B., Robinsonm, N. et al. Safety, tolerability, and pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole utrophin modulator, following single- and multiple-dose administration to pediatric patients with Duchenne muscular dystrophy. PLoS ONE 11, e0152840 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Messina, S., Bitto, A., Vita, G. L., Aguennouz, M., Irrera, N., Licata, N. et al. Modulation of neuronal nitric oxide synthase and apoptosis by the isoflavone genistein in Mdx mice. Biofactors 41, 324–329 (2015).

    CAS  Article  Google Scholar 

  22. 22

    Wilton, S. D., Dye, D. E., Blechynden, L. M. & Laing, N. G. Revertant fibres: a possible genetic therapy for Duchenne muscular dystrophy? Neuromuscl. Disord. 7, 329–335 (1997).

    CAS  Article  Google Scholar 

  23. 23

    Crawford, G. E., Lu, Q. L., Partridge, T. A. & Chamberlain, J. S. Suppression of revertant fibers in mdx mice by expression on a functional dystrophin. Hum. Mol. Genet. 10, 2745–2750 (2001).

    CAS  Article  Google Scholar 

  24. 24

    Nakamura, A. & Takeda, S. Exon-skipping therapy for Duchenne muscular dystrophy. Neuropathology 29, 494–501 (2009).

    Article  Google Scholar 

  25. 25

    Echigoya, Y., Mouly, V., Garcia, L., Yokota, T. & Duddy, W. In silico screening based on predictive algorithms as a design tool for exon skipping of oligonucleotides in Duchenne muscular dystrophy. PLoS ONE 10, e0120058 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26

    Nakamura, A. & Takeda, S. Mammalian models of Duchenne muscular dystrophy: pathological characteristics and therapeutic applications. J. Biomed. Biotechnol. 2011, 184393 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    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 81, 1189–1192 (1984).

    CAS  Article  Google Scholar 

  28. 28

    Tanabe, Y., Esaki, K. & Nomura, T. Skeletal muscle pathology in X chromosome-linked muscular dystrophy (mdx) mouse. Acta Neuropathol. 79, 91–95 (1986).

    Article  Google Scholar 

  29. 29

    Dunckley, M. G., Manoharan, M., Villiet, P., Eperon, I. C. & Dickson, G. Modification of splicing in the dystrophin gene in cultured Mdx muscle cells by antisense oligoribonucleotides. Hum. Mol. Genet. 7, 1083–1090 (1998).

    CAS  Article  Google Scholar 

  30. 30

    Mann, C. J., Honeyman, K., Cheng, A. J., Ly, T., Lloyd, F., Fletcher, S. et al. Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse. Proc. Natl Acad. Sci. USA 98, 42–47 (2001).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31

    Lu, Q. L., Mann, C. J., Lou, F., Bou-Gharios, G., Morris, G. E., Xue, S. A. et al. Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat. Med. 9, 1009–1014 (2003).

    CAS  Article  Google Scholar 

  32. 32

    Lu, Q. L., Rabinowitz, A., Chen, Y. C., 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. USA 102, 198–203 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33

    Wells, K. E., Fletcher, S., Mann, C. J., Wilton, S. D. & Wells, D. J. Enhanced in vivo delivery of antisense oligonucleotides to restore dystrophin expression in adult mdx mouse muscle. FEBS Lett. 552, 145–149 (2003).

    CAS  Article  Google Scholar 

  34. 34

    Fletcher, S., Honeyman, K., Fall, A. M., Harding, P. L., Johnsen, R. D. & Wilton, S. D. Dystrophin expression in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide. J. Gene Med. 8, 207–216 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35

    Alter, J., Lou, F., Rabinowitz, A., Yin, H., Rosenfeld, J., Wilton, S. D. et al. Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology. Nat. Med. 12, 175–177 (2006).

    CAS  Article  Google Scholar 

  36. 36

    Cooper, B. J., Winand, N. J., Stedman, H., Valentine, B. A., Hoffman, E. P., Kunkel, L. M. et al. The homologue of the Duchenne locus in defective in X-linked muscular dystrophy of dogs. Nature 334, 154–156 (1988).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37

    Valentine, B. A., Cooper, B. J., De Lahunta, R., Valentine, B. A., Hoffman, E. P., Kunkel, L. M. et al. Canine X-linked muscular dystrophy. An animal model of Duchenne muscular dystrophy: clinical studies. J. Neurol. Sci. 88, 69–81 (1988).

    CAS  Article  Google Scholar 

  38. 38

    Sharp, N. J. H., Kornegay, J. N., van Camp, S. D., Herbstreith, M. H., Secore, S. L., Kettle, S. et al. An error in dystrophin mRNA processing in golden retriever muscular dystrophy, an animal homologue of Duchenne muscular dystrophy. Genomics 13, 115–121 (1992).

    CAS  Article  PubMed  Google Scholar 

  39. 39

    Shimatsu, Y., Katagiri, K., Furuta, T., Nakura, M., Tanioka, Y., Yuasa, K. et al. Canine X-linked muscular dystrophy in Japan (CXMDJ . Exp. Anim. 52, 93–97 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Shimatsu, Y., Yoshimura, M., Yuasa, K., Urasawa, N., Tomohiro, M., Nakura, M. et al. Major clinical and histopathological characteristics of canine X-linked muscular dystrophy in Japan, CXMDJ . Acta Myol. 24, 145–154 (2005).

    CAS  Google Scholar 

  41. 41

    Yugeta, N., Urasawa, N., Fujii, Y., Yoshimura, M., Yuasa, K., Wada, M. R. et al. Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ: electrocardiographic, echocardiographic, and morphologic studies. BMC Cardiovasc. Disord. 6, 47 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42

    Yokota, T., Lu, Q. L., Partridge, T., Kobayashi, M., Nakamura, A., Takeda, S. et al. Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs. Ann. Neurol. 65, 667–676 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  43. 43

    Curran, F. J. & Colbert, A. P. Ventilator management in Duchenne muscular dystrophy and postpoliomyelitis syndrome: twelve years’ experience. Arch. Phys. Med. Rehabil. 70, 180–185 (1989).

    CAS  Google Scholar 

  44. 44

    Jearawiriyapaisarn, N., Moulton, H. M., Buckley, B., Roberts, J., Sazani, P., Fucharoen, S. et al. Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscle of mdx mice. Mol. Ther. 16, 1624–1629 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45

    Beroud, C., Tuffery-Giraud, S., Matsuo, M., Hamroun, D., Humbertclaude, V., Monnier, N. et al. Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy. Hum. Mutat. 28, 196–202 (2007).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. 46

    Bladen, C. L., Salgado, D., Monges, S., Foncuberta, M. E., Kekou, K., Kosma, K. et al. The TREAT-NMD DMD Global Database: analysis of more than 7000 Duchenne muscular dystrophy mutations. Hum. Mutat. 36, 395–402 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47

    Araki, E., Nakamura, K., Nakao, K., Kameya, S., Kobayashi, O., Nonaka, I. et al. Targeted disruption of exon 52 in the mouse dystrophin gene induced muscle degeneration similar to that observed in Duchenne muscular dystrophy. Biochem. Biophys. Res. Commun. 238, 492–497 (1997).

    CAS  Article  Google Scholar 

  48. 48

    Kameya, S., Araki, E., Katsuki, M., Mizota, A., Adachi, E., Nakahara, K. et al. Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of beta-dystroglycan in the outer plexiform layer of the retina. Hum. Mol. Genet. 6, 2195–2203 (1997).

    CAS  Article  Google Scholar 

  49. 49

    Aoki, Y., Nakamura, A., Yokota, T., Saito, T., Okazawa, H., Nagata, T. et al. In-frame dystrophin following exon 51-skipping improves muscle pathology and function in the exon 52-deficient mdx mouse. Mol. Ther. 18, 1995–2005 (2010).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50

    Servais, L., Montus, M., Guiner, C. L., Ben Yaou, R., Annoussamy, M., Moraux, A. et al. Non-ambulant Duchenne patients theoretically treatable by exon 53 skipping have severe phenotype. J. Neuromuscul. Dis. 2, 269–279 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51

    van Deutekom, J. C., Janson, A. A., Ginjaar, I. B., Frankhuizen, W. S., Aartsma-Rus, A., Bremmer-Bout, M. et al. Local dystrophin restoration with antisense oligonucleotide PRO051. N. Engl. J. Med. 357, 2677–2686 (2007).

    CAS  Article  Google Scholar 

  52. 52

    Voit, T., Topaloglu, H., Straub, V., Muntoni, F., Deconinck, N., Campion, G. 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. 13, 987–996 (2014).

    CAS  Article  Google Scholar 

  53. 53

    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 378, 595–605 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54

    Goemans, N. M., Tulinius, M., van den Hauwe, M., Kroksmark, A. K., Buyse, G., Wilson, R. J. et al. Long-term efficacy, safety, and pharmacokinetics of drisapersen in Duchenne muscular dystrophy: results from an open-label extension study. PLoS ONE 11, e0161955 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55

    Syed, Y. Y. Eteplirsen: first global approval. Drugs 76, 1699–1704 (2016).

    CAS  Article  Google Scholar 

  56. 56

    Carver, M. P., Charleston, J. S., Shanks, C., Zhang, J., Mense, M., Sharma, A. K. et al. Toxicological characterization of exon skipping phosphorodiamidate morpholino oligomers (PMOs) in non-human primates. J. Neuromuscul. Dis. 3, 381–393 (2016).

    Article  Google Scholar 

  57. 57

    Betts, C. A., Hammond, S. M., Yin, H. F. & Wood, M. J. Optimizing tissue-specific antisense oligonucleotide-peptide conjugates. Methods Mol. Biol. 867, 415–435 (2012).

    CAS  Article  Google Scholar 

  58. 58

    Aoki, Y., Nagata, T., Yokota, T., Nakamura, A., Wood, M. J., Partridge, T. et al. High efficient in vivo delivery of PMO in to regenerating myotubes and rescue in laminin-α2 chain null congenital muscular dystrophy mice. Hum. Mol. Genet. 22, 4914–4928 (2013).

    CAS  Article  Google Scholar 

  59. 59

    Ezzat, K., Aoki, Y., Koo, T., McClorey, G., Benner, L., Coenen-Stass, A. et al. Self-assembly into nanoparticles is essential for receptor mediated uptake of therapeutic antisense oligonucleotides. Nano Lett. 15, 4364–4373 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60

    Nakamura, A., Yoshida, K., Fukushima, K., Ueda, H., Urasawa, N., Koyama, J. et al. Follow-up of three patients with a large in-frame deletion of exons 45-55 in the Duchenne muscular dystrophy (DMD) gene. J. Clin. Neurosci. 15, 757–763 (2008).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  61. 61

    Taglia, A., Petillo, R., D’Ambrosio, P., Picillo, E., Torella, A., Orsini, C. et al. Clinical features pf patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene. Acta Myol. 34, 9–13 (2015).

    PubMed  PubMed Central  Google Scholar 

  62. 62

    Nakamura, A. & Takeda, S. Exon skipping therapy for Duchenne muscular dystrophy. Lancet 378, 546–547 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  63. 63

    Aoki, Y., Yokota, T., Nagata, T., Nakamura, A., Tanihata, J., Saito, T. et al. Bodywide skipping of exons 45-55 in dystrophic mdx52 mice by systemic antisense delivery. Proc. Natl Acad. Sci. USA 109, 13763–13768 (2012).

    CAS  Article  Google Scholar 

  64. 64

    Nakamura, A., Shiba, N., Miyazaki, D., Nishizawa, H., Inaba, Y., Fueki, N. et al. Comparison of the phenotypes of patients harboring in-frame deletions starting at exon 45 in the Duchenne muscular dystrophy gene indicates potential for the development of exon skipping therapy. J. Hum. Genet. 62, 459–463 (2016).

    Article  Google Scholar 

  65. 65

    Nicolas, A., Raguénès-Nicol, C., Ben Yaou, R., Ameziane-Le Hir, S., Chéron, A., Vié, V. et al. Becker muscular dystrophy severity is linked to the structure of dystrophin. Hum. Mol. Genet. 24, 1267–1279 (2015).

    CAS  Article  Google Scholar 

  66. 66

    Nakamura, A., Fueki, N., Shiba, N., Motoki, H., Miyazaki, D., Nishizawa, H. et al. Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy. J. Hum. Genet. 61, 663–667 (2016).

    CAS  Article  Google Scholar 

  67. 67

    Pane, M., Mazzone, E. S., Sivo, S., Sormani, M. P., Messina, S., D’Amico, A. et al. Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes. PLoS ONE 9, e108205 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  68. 68

    De Sanctis, R., Pane, M., Sivo, S., Ricotti, V., Baranello, G., Frosini, S. et al. Suitability of North Star Ambulatory Assessment in young boys with Duchenne muscular dystrophy. Neuromuscul. Disord. 25, 14–18 (2015).

    Article  Google Scholar 

  69. 69

    Kimura, S., Ozasa, S., Nomura, K., Yoshioka, K. & Endo, F. Estimation of muscle strength from actigraph data in Duchenne muscular dystrophy. Pediatr. Int. 56, 748–752 (2014).

    Article  Google Scholar 

  70. 70

    Nishizawa, H., Shiba, N. & Nakamura, A. Usefulness of continuous actigraph monitoring in the assessment of the effect of corticosteroid treatment for Duchenne muscular dystrophy: a case report. J. Phys. Ther. Sci. 28, 3249–3251 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

Download references


This study was supported by an Intramural Research Grant (26-6) for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry (to AN).

Author information



Corresponding author

Correspondence to Akinori Nakamura.

Ethics declarations

Competing interests

The author declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nakamura, A. Moving towards successful exon-skipping therapy for Duchenne muscular dystrophy. J Hum Genet 62, 871–876 (2017).

Download citation

Further reading


Quick links