CoChat
Sign Up
Cited by 85Virus-based gene therapy researchNeurogenetic and Muscular Disorders ResearchMuscle Physiology and Disorders

AAV-microdystrophin Therapy Improves Cardiac Performance in Aged Female mdx Mice

Open access
Bostick, Brian, Shin, Jin-Hong, Yue, Yongping, Duan, Dongsheng·2011·Molecular Therapy
DOI 10.1038/mt.2011.154PMC PMC3188746
Open this paper in CoChat — free accountOpen PDF

Abstract

Dystrophin deficiency leads to lethal dilated Duchenne cardiomyopathy. A promising therapy is to deliver a highly abbreviated microdystrophin gene to the heart using adeno-associated virus (AAV). Microdystrophin has been shown to mitigate dystrophin-deficient skeletal muscle disease. However, it is not clear whether microdystrophin is equally effective in treating Duchenne cardiomyopathy. To evaluate microdystrophin therapy in the heart, we injected 5 × 10(12) viral genome particles/mouse of AAV-9 ΔR4-23/ΔC microdystrophin vector via tail vein to ~16-20-month-old (average 18.7-month-old) female mdx mice, a manifesting model of Duchenne cardiomyopathy. Cardiac transduction and heart function were examined at 2-8 months after gene transfer. We observed robust myocardial microdystrophin expression. Electrocardiography (ECG) and left ventricular catheter hemodynamic assays also revealed significant improvement. Furthermore, AAV-microdystrophin therapy prevented dobutamine-stress induced acute cardiac death. We demonstrate for the first time that AAV microdystrophin therapy significantly ameliorates functional deficiency in a phenotypic model of Duchenne cardiomyopathy. Our results support further exploration of microdystrophin therapy to treat Duchenne cardiomyopathy.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/mt.2011.154

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 37

  1. [1]1. American Academy of Pediatrics, Section on Cardiology and Cardiac Surgery Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy Pediatrics. 2005; 116:1569-1573 Crossref Scopus (185) PubMed Google Scholar
  2. [3]3. Shin, J-H ∙ Bostick, B ∙ Yue, Y ... Duchenne cardiomyopathy gene therapy Duan, D (Editor) Muscle Gene Therapy Springer Science + Business Media, LLC, New York, 2010; 141-162 Crossref Scopus (9) Google Scholar
  3. [4]4. Gregorevic, P ∙ Blankinship, MJ ∙ Allen, JM ... Systemic delivery of genes to striated muscles using adeno-associated viral vectors Nat Med. 2004; 10:828-834 Crossref Scopus (564) PubMed Google Scholar
  4. [5]5. Wang, Z ∙ Zhu, T ∙ Qiao, C ... Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart Nat Biotechnol. 2005; 23:321-328 Crossref Scopus (526) PubMed Google Scholar
  5. [6]6. Pacak, CA ∙ Mah, CS ∙ Thattaliyath, BD ... Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo Circ Res. 2006; 99:e3-e9 Crossref Scopus (331) PubMed Google Scholar
  6. [7]7. Bostick, B ∙ Ghosh, A ∙ Yue, Y ... Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration Gene Ther. 2007; 14:1605-1609 Crossref Scopus (146) PubMed Google Scholar
  7. [8]8. England, SB ∙ Nicholson, LV ∙ Johnson, MA ... Very mild muscular dystrophy associated with the deletion of 46% of dystrophin Nature. 1990; 343:180-182 Crossref Scopus (544) PubMed Google Scholar
  8. [9]9. Fanin, M ∙ Freda, MP ∙ Vitiello, L ... Duchenne phenotype with in-frame deletion removing major portion of dystrophin rod: threshold effect for deletion size Muscle Nerve. 1996; 19:1154-1160 Crossref Scopus (47) PubMed Google Scholar
  9. [10]10. Yue, Y ∙ Liu, M ∙ Duan, D C-terminal-truncated microdystrophin recruits dystrobrevin and syntrophin to the dystrophin-associated glycoprotein complex and reduces muscular dystrophy in symptomatic utrophin/dystrophin double-knockout mice Mol Ther. 2006; 14:79-87 Full Text Full Text (PDF) Scopus (64) PubMed Google Scholar
  10. [11]11. Gregorevic, P ∙ Blankinship, MJ ∙ Allen, JM ... Systemic microdystrophin gene delivery improves skeletal muscle structure and function in old dystrophic mdx mice Mol Ther. 2008; 16:657-664 Full Text Full Text (PDF) Scopus (104) PubMed Google Scholar
  11. [12]12. Gregorevic, P ∙ Allen, JM ∙ Minami, E ... rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice Nat Med. 2006; 12:787-789 Crossref Scopus (262) PubMed Google Scholar
  12. [13]13. Bostick, B ∙ Yue, Y ∙ Long, C ... Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged Mdx mice Mol Ther. 2009; 17:253-261 Full Text Full Text (PDF) Scopus (78) PubMed Google Scholar
  13. [14]14. Yue, Y ∙ Skimming, JW ∙ Liu, M ... Full-length dystrophin expression in half of the heart cells ameliorates beta-isoproterenol-induced cardiomyopathy in mdx mice Hum Mol Genet. 2004; 13:1669-1675 Crossref Scopus (60) PubMed Google Scholar
  14. [15]15. Yue, Y ∙ Li, Z ∙ Harper, SQ ... Microdystrophin gene therapy of cardiomyopathy restores dystrophin-glycoprotein complex and improves sarcolemma integrity in the mdx mouse heart Circulation. 2003; 108:1626-1632 Crossref Scopus (137) PubMed Google Scholar
  15. [16]16. Danialou, G ∙ Comtois, AS ∙ Dudley, R ... Dystrophin-deficient cardiomyocytes are abnormally vulnerable to mechanical stress-induced contractile failure and injury FASEB J. 2001; 15:1655-1657 Crossref Scopus (153) PubMed Google Scholar
  16. [17]17. Van Erp, C ∙ Loch, D ∙ Laws, N ... Timeline of cardiac dystrophy in 3-18-month-old MDX mice Muscle Nerve. 2010; 42:504-513 Crossref Scopus (46) PubMed Google Scholar
  17. [18]18. Quinlan, JG ∙ Hahn, HS ∙ Wong, BL ... Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings Neuromuscul Disord. 2004; 14:491-496 Full Text Full Text (PDF) Scopus (227) PubMed Google Scholar
  18. [19]19. Lefaucheur, JP ∙ Pastoret, C ∙ Sebille, A Phenotype of dystrophinopathy in old mdx mice Anat Rec. 1995; 242:70-76 Crossref Scopus (172) PubMed Google Scholar
  19. [20]20. Wehling-Henricks, M ∙ Jordan, MC ∙ Roos, KP ... Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium Hum Mol Genet. 2005; 14:1921-1933 Crossref Scopus (126) PubMed Google Scholar
  20. [21]21. Bostick, B ∙ Yue, Y ∙ Long, C ... Prevention of dystrophin-deficient cardiomyopathy in twenty-one-month-old carrier mice by mosaic dystrophin expression or complementary dystrophin/utrophin expression Circ Res. 2008; 102:121-130 Crossref Scopus (98) PubMed Google Scholar
  21. [22]22. Bostick, B ∙ Yue, Y ∙ Duan, D Gender influences cardiac function in the mdx model of Duchenne cardiomyopathy Muscle Nerve. 2010; 42:600-603 Crossref Scopus (49) PubMed Google Scholar
  22. [23]23. Bostick, B ∙ Yue, Y ∙ Lai, Y ... Adeno-associated virus serotype-9 microdystrophin gene therapy ameliorates electrocardiographic abnormalities in mdx mice Hum Gene Ther. 2008; 19:851-856 Crossref Scopus (87) PubMed Google Scholar
  23. [24]24. Ghosh, A ∙ Yue, Y ∙ Shin, JH ... 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 Crossref Scopus (39) PubMed Google Scholar
  24. [25]25. Townsend, D ∙ Blankinship, MJ ∙ Allen, JM ... Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure Mol Ther. 2007; 15:1086-1092 Full Text Full Text (PDF) Scopus (116) PubMed Google Scholar
  25. [26]26. Katz, MG ∙ Swain, JD ∙ White, JD ... Cardiac gene therapy: optimization of gene delivery techniques in vivo Hum Gene Ther. 2010; 21:371-380 Crossref Scopus (36) PubMed Google Scholar
  26. [27]27. Ly, HQ ∙ Kawase, Y ∙ Hajjar, RJ Advances in gene-based therapy for heart failure J Cardiovasc Transl Res. 2008; 1:127-136 Crossref Scopus (6) PubMed Google Scholar
  27. [28]28. Jefferies, JL ∙ Eidem, BW ∙ Belmont, JW ... Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy Circulation. 2005; 112:2799-2804 Crossref Scopus (233) PubMed Google Scholar
  28. [29]29. Kaspar, RW ∙ Allen, HD ∙ Ray, WC ... Analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in becker muscular dystrophy Circ Cardiovasc Genet. 2009; 2:544-551 Crossref Scopus (131) PubMed Google Scholar
  29. [30]30. Lai, Y ∙ Yue, Y ∙ Bostick, B ... Delivering large therapeutic genes for muscle gene therapy Duan, D (Editor) Muscle Gene Therapy Springer Science + Business Media, LLC, New York, 2010; 205-218 Crossref Scopus (11) Google Scholar
  30. [31]31. Harper, SQ ∙ Hauser, MA ∙ DelloRusso, C ... Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy Nat Med. 2002; 8:253-261 Crossref Scopus (490) PubMed Google Scholar
  31. [32]32. 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 USA. 2000; 97:13714-13719 Crossref Scopus (429) PubMed Google Scholar
  32. [33]33. Lai, Y ∙ Thomas, GD ∙ Yue, Y ... 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. 2009; 119:624-635 Crossref Scopus (310) PubMed Google Scholar
  33. [34]34. Trollet, C ∙ Athanasopoulos, T ∙ Popplewell, L ... Gene therapy for muscular dystrophy: current progress and future prospects Expert Opin Biol Ther. 2009; 9:849-866 Crossref Scopus (44) PubMed Google Scholar
  34. [35]35. Odom, GL ∙ Gregorevic, P ∙ Chamberlain, JS Viral-mediated gene therapy for the muscular dystrophies: successes, limitations and recent advances Biochim Biophys Acta. 2007; 1772:243-262 Crossref Scopus (87) PubMed Google Scholar
  35. [36]36. Muntoni, F ∙ Di Lenarda, A ∙ Porcu, M ... Dystrophin gene abnormalities in two patients with idiopathic dilated cardiomyopathy Heart. 1997; 78:608-612 Crossref Scopus (77) PubMed Google Scholar
  36. [37]37. Melacini, P ∙ Fanin, M ∙ Danieli, GA ... Myocardial involvement is very frequent among patients affected with subclinical Becker's muscular dystrophy Circulation. 1996; 94:3168-3175 Crossref Scopus (180) PubMed Google Scholar
  37. [38]38. Melis, MA ∙ Cau, M ∙ Muntoni, F ... Elevation of serum creatine kinase as the only manifestation of an intragenic deletion of the dystrophin gene in three unrelated families Eur J Paediatr Neurol. 1998; 2:255-261

Cited by

Sorted by citations

Authors
Bostick, B., Shin, J.-H., Yue, Y., & Duan, D.
Affiliations
University of Missouri (US)
Corresponding author
Duan, Dongsheng
ORCID
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2011-10
Volume
19
Issue
10
Pages
1826-1832
ISSN
1525-0016 (ISSN-L)
DOI
10.1038/mt.2011.154
PMC
PMC3188746
OpenAlex
W2000168224
Cited by
85
References
0
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 9 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 5
FWCI
2.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL091883, HL-91883)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
Duchenne cardiomyopathy, microdystrophin, adeno-associated virus gene therapy, mdx mice, dystrophin deficiency, cardiac function
MeSH terms
Dependovirus, Aging, Animals, Dobutamine, Electrocardiography, Female, Genetic Vectors, Heart Function Tests, Hemodynamics, Transduction, Genetic, Dystrophin, Mice, Inbred mdx, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review