inbred mdx mice

Summary

Summary: A strain of mice arising from a spontaneous MUTATION (mdx) in inbred C57BL mice. This mutation is X chromosome-linked and produces viable homozygous animals that lack the muscle protein DYSTROPHIN, have high serum levels of muscle ENZYMES, and possess histological lesions similar to human MUSCULAR DYSTROPHY. The histological features, linkage, and map position of mdx make these mice a worthy animal model of DUCHENNE MUSCULAR DYSTROPHY.

Top Publications

  1. ncbi Long-term administration of pirfenidone improves cardiac function in mdx mice
    Christel Van Erp
    Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland 4350, Australia
    Muscle Nerve 34:327-34. 2006
  2. ncbi Systemic administration of L-arginine benefits mdx skeletal muscle function
    Elisabeth R Barton
    Department of Anatomy and Cell Biology, School of Dental Medicine, 441 Levy Building, 240 South 40th Street, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Muscle Nerve 32:751-60. 2005
  3. ncbi Expression of dystrophin driven by the 1.35-kb MCK promoter ameliorates muscular dystrophy in fast, but not in slow muscles of transgenic mdx mice
    Patrick Dunant
    Gene Center, Friedrich Baur Institute, and Department of Neurology, Ludwig Maximilians University, 81377, Munich, Germany
    Mol Ther 8:80-9. 2003
  4. ncbi Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophy
    Christopher J Mann
    Australian Neuromuscular Research Institute, Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia, 6907
    J Gene Med 4:644-54. 2002
  5. ncbi Helper (CD4(+)) and cytotoxic (CD8(+)) T cells promote the pathology of dystrophin-deficient muscle
    M J Spencer
    Department of Pediatrics, University of California at Los Angeles, California 90095-1606, USA
    Clin Immunol 98:235-43. 2001
  6. pmc Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration
    Zhuqing Qu-Petersen
    Growth and Development Laboratory, Children s Hospital of Pittsburgh, Department of Orthopaedic Surgery, University of Pittsburgh, PA 15260, USA
    J Cell Biol 157:851-64. 2002
  7. ncbi Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy
    R M Grady
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell 90:729-38. 1997
  8. ncbi Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
    A E Deconinck
    Department of Biochemistry, University of Oxford, United Kingdom
    Cell 90:717-27. 1997
  9. ncbi Absence of integrin alpha 7 causes a novel form of muscular dystrophy
    U Mayer
    Max Planck Institute for Biochemistry, Martinsried, Germany
    Nat Genet 17:318-23. 1997
  10. pmc Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibers detected with Ca2+-activated K+ channels
    N Mallouk
    Laboratoire de Physiologie des Elements Excitables, Unite Mixte de Recherche, Centre National de la Recherche Scientifique 5578, Universite Claude Bernard Lyon I, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
    Proc Natl Acad Sci U S A 97:4950-5. 2000

Detail Information

Publications307 found, 100 shown here

  1. ncbi Long-term administration of pirfenidone improves cardiac function in mdx mice
    Christel Van Erp
    Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland 4350, Australia
    Muscle Nerve 34:327-34. 2006
    ..These results show that the TGF-beta antagonist, pirfenidone, can improve cardiac function in mdx mice, potentially providing a new avenue for developing cardiac therapies for patients with Duchenne muscular dystrophy...
  2. ncbi Systemic administration of L-arginine benefits mdx skeletal muscle function
    Elisabeth R Barton
    Department of Anatomy and Cell Biology, School of Dental Medicine, 441 Levy Building, 240 South 40th Street, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Muscle Nerve 32:751-60. 2005
    ..Together, these results show that L-arginine treatment can be beneficial to mdx muscle function, perhaps through a combination of enhanced calcium handling and increased utrophin, thereby decreasing muscle degeneration...
  3. ncbi Expression of dystrophin driven by the 1.35-kb MCK promoter ameliorates muscular dystrophy in fast, but not in slow muscles of transgenic mdx mice
    Patrick Dunant
    Gene Center, Friedrich Baur Institute, and Department of Neurology, Ludwig Maximilians University, 81377, Munich, Germany
    Mol Ther 8:80-9. 2003
    ..Additionally, expression was strong in glycolytic but weak in oxidative fibers of fast-twitch muscles. This study may have important implications for the design of future gene therapy trials for muscular dystrophy...
  4. ncbi Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophy
    Christopher J Mann
    Australian Neuromuscular Research Institute, Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia, 6907
    J Gene Med 4:644-54. 2002
    ..We have investigated and improved the design of AOs capable of removing exon 23, and thus the disease-causing nonsense mutation, from mRNA in the mdx mouse model of DMD...
  5. ncbi Helper (CD4(+)) and cytotoxic (CD8(+)) T cells promote the pathology of dystrophin-deficient muscle
    M J Spencer
    Department of Pediatrics, University of California at Los Angeles, California 90095-1606, USA
    Clin Immunol 98:235-43. 2001
    ..These results indicate that T cells promote the mdx pathology and suggest that immune-based therapies may provide benefit to DMD patients...
  6. pmc Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration
    Zhuqing Qu-Petersen
    Growth and Development Laboratory, Children s Hospital of Pittsburgh, Department of Orthopaedic Surgery, University of Pittsburgh, PA 15260, USA
    J Cell Biol 157:851-64. 2002
    ..Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell-mediated therapies...
  7. ncbi Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy
    R M Grady
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell 90:729-38. 1997
    ..Thus, utrophin attenuates the effects of dystrophin deficiency, and the double mutant may provide a useful model for studies of pathogenesis and therapy...
  8. ncbi Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
    A E Deconinck
    Department of Biochemistry, University of Oxford, United Kingdom
    Cell 90:717-27. 1997
    ..Detailed study of these mice should provide novel insights into the pathogenesis of DMD and provide an improved model for rapid evaluation of gene therapy strategies...
  9. ncbi Absence of integrin alpha 7 causes a novel form of muscular dystrophy
    U Mayer
    Max Planck Institute for Biochemistry, Martinsried, Germany
    Nat Genet 17:318-23. 1997
    ....
  10. pmc Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibers detected with Ca2+-activated K+ channels
    N Mallouk
    Laboratoire de Physiologie des Elements Excitables, Unite Mixte de Recherche, Centre National de la Recherche Scientifique 5578, Universite Claude Bernard Lyon I, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
    Proc Natl Acad Sci U S A 97:4950-5. 2000
    ..These data favor the hypothesis according to which an increased calcium entry is associated with the absence of dystrophin in mdx skeletal muscle, leading to Ca(2+) overload at the subsarcolemmal level...
  11. ncbi Anti-TNFalpha (Remicade) therapy protects dystrophic skeletal muscle from necrosis
    Miranda D Grounds
    School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Hwy, Crawley, Western Australia, Australia 6009
    FASEB J 18:676-82. 2004
    ..Remicade is a highly specific anti-inflammatory intervention, and clinical application to muscular dystrophies is suggested by this marked protective effect against skeletal muscle breakdown...
  12. ncbi Histological parameters for the quantitative assessment of muscular dystrophy in the mdx-mouse
    Alexandre Briguet
    MyoContract Ltd, Hammerstrasse 25, CH 4410 Liestal, Switzerland
    Neuromuscul Disord 14:675-82. 2004
    ..In addition, we compare the variance coefficients of the muscle fiber size with the percentage of muscle fibers with centralized nuclei; another histological hallmark of muscular dystrophy...
  13. pmc Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling
    R Turk
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, Nederland
    BMC Genomics 6:98. 2005
    ..To characterize the molecular processes associated with regeneration, we compared gene expression levels in hindlimb muscle tissue of mdx and control mice at 9 timepoints, ranging from 1-20 weeks of age...
  14. ncbi Functional improvement of dystrophic muscle by myostatin blockade
    Sasha Bogdanovich
    Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Richards A 601, Philadelphia, Pennsylvania 19104 6085, USA
    Nature 420:418-21. 2002
    ....
  15. pmc In situ measurements of calpain activity in isolated muscle fibres from normal and dystrophin-lacking mdx mice
    P Gailly
    Laboratory of Cell Physiology, Catholic University of Louvain, 1200 Brussels, Belgium
    J Physiol 582:1261-75. 2007
    ....
  16. ncbi Reduced necrosis of dystrophic muscle by depletion of host neutrophils, or blocking TNFalpha function with Etanercept in mdx mice
    Stuart Hodgetts
    School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia
    Neuromuscul Disord 16:591-602. 2006
    ..Etanercept is a highly specific anti-inflammatory drug, widely used clinically, and potential application to muscular dystrophies is suggested by this reduced breakdown of mdx skeletal muscle...
  17. ncbi PTC124 targets genetic disorders caused by nonsense mutations
    Ellen M Welch
    PTC Therapeutics, 100 Corporate Court, South Plainfield, New Jersey 07080, USA
    Nature 447:87-91. 2007
    ....
  18. pmc A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cells
    J E Anderson
    Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3
    Mol Biol Cell 11:1859-74. 2000
    ..A model proposes the hypothesis that NO release mediates satellite cell activation, possibly via shear-induced rapid increases in NOS activity that produce "NO transients."..
  19. pmc Effects of stretch-activated channel blockers on [Ca2+]i and muscle damage in the mdx mouse
    Ella W Yeung
    School of Medical Sciences and Institute for Biomedical Research, University of Sydney F13, NSW 2006, Australia
    J Physiol 562:367-80. 2005
    ..This result suggests that blockers of stretch-activated channels may protect against muscle damage in the intact mdx mouse...
  20. pmc Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx mice
    Natee Jearawiriyapaisarn
    Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Mol Ther 16:1624-9. 2008
    ..This is the first report of oligonucleotide-mediated exon skipping and dystrophin protein induction in the heart of treated animals...
  21. ncbi T-cell-dependent fibrosis in the mdx dystrophic mouse
    J Morrison
    Muscle Cell Biology Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
    Lab Invest 80:881-91. 2000
    ..This suggests that T-cells play a role in the onset of the fibrotic events that undermines the ability of dystrophic muscle to regenerate...
  22. pmc Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane
    Cosimo De Bari
    Laboratory for Skeletal Development and Joint Disorders, Dept of Rheumatology, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium
    J Cell Biol 160:909-18. 2003
    ..When administered into dystrophic muscles of immunosuppressed mdx mice, hSM-MSCs restored sarcolemmal expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor...
  23. ncbi The role of reactive oxygen species in the hearts of dystrophin-deficient mdx mice
    Iwan A Williams
    Bosch Institute, School of Medical Sciences, University of Sydney F13, NSW 2006 Australia
    Am J Physiol Heart Circ Physiol 293:H1969-77. 2007
    ..Therapies designed to reduce oxidative damage might be beneficial to DMD patients with heart failure...
  24. pmc The action potential-evoked sarcoplasmic reticulum calcium release is impaired in mdx mouse muscle fibres
    Christopher E Woods
    Department of Physiology, UCLA School of Medicine, Los Angeles, CA 90095, USA
    J Physiol 557:59-75. 2004
    ..Since the myoplasmic Ca(2+) concentration is a critical regulator of muscle contraction, these results may help to explain the weakness observed in skeletal muscle fibres from mdx mice and, possibly, Duchenne muscular dystrophy patients...
  25. ncbi Why do cultured transplanted myoblasts die in vivo? DNA quantification shows enhanced survival of donor male myoblasts in host mice depleted of CD4+ and CD8+ cells or Nk1.1+ cells
    S I Hodgetts
    Department of Anatomy and Human Biology, The University of Western Australia, Nedlands, Perth
    Cell Transplant 9:489-502. 2000
    ..These results provide a strategic approach to enhance donor myoblast survival in clinical trials of MTT...
  26. ncbi Differential expression of dystrophin isoforms in strains of mdx mice with different mutations
    W B Im
    Upjohn Company, Kalamazoo, MI 49001, USA
    Hum Mol Genet 5:1149-53. 1996
    ..The mdx4cv and mdx5cv strains may be of additional use in gene transfer studies due to their low frequency of mutation reversion...
  27. ncbi Leukemia inhibitory factor and interleukin-6 are produced by diseased and regenerating skeletal muscle
    J B Kurek
    Melbourne Neuromuscular Research Centre, St Vincent s Hospital, Fitzroy, Victoria, Australia
    Muscle Nerve 19:1291-301. 1996
    ....
  28. pmc Massive idiosyncratic exon skipping corrects the nonsense mutation in dystrophic mouse muscle and produces functional revertant fibers by clonal expansion
    Q L Lu
    Muscle Cell Biology, Medical Research Council Clinical Science Center, Hammersmith Hospital, London W12 ONN, UK
    J Cell Biol 148:985-96. 2000
    ..The dystrophin gene in the mdx mouse provides a favored system for study of exon skipping associated with nonsense mutations...
  29. ncbi Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice
    Masashi Nakatani
    Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Sciences ICMS, Fujita Health University, Toyoake, Aichi 470 1192, Japan
    FASEB J 22:477-87. 2008
    ..Muscle strength is also recovered in the mdx/FS I-I mice. These results indicate that myostatin blockade by FS I-I has a therapeutic potential for muscular dystrophy...
  30. ncbi Expansion of revertant fibers in dystrophic mdx muscles reflects activity of muscle precursor cells and serves as an index of muscle regeneration
    Toshifumi Yokota
    Muscle Cell Biology Group, Medical Research Council Clinical Science Centre, Hammersmith Hospital Campus, Imperial College School of Medicine, London University, Du Cane Road, London, W12 0NN, UK
    J Cell Sci 119:2679-87. 2006
    ..This expansion of revertant clusters depicts the cumulative history of regeneration, thus providing a useful index for functional evaluation of therapies that counteract muscle degeneration...
  31. ncbi Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system
    S Squire
    MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK
    Hum Mol Genet 11:3333-44. 2002
    ..The new model shows that utrophin therapy, initiated after birth, can be effective, but the extent of correction of the various symptoms of dystrophinopathy critically depends on the amount of utrophin expressed...
  32. ncbi rAAV6-microdystrophin rescues aberrant Golgi complex organization in mdx skeletal muscles
    Justin M Percival
    Department of Physiology and Biophysics, University of Washington, Box 357290, 1959 NE Pacific Street, Seattle, WA 98195, USA
    Traffic 8:1424-39. 2007
    ..In summary, GC distribution abnormalities are a novel component of mdx skeletal muscle pathology rescued by microdystrophin expression...
  33. ncbi Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides
    S D Wilton
    Department of Pathology, Australian Neuromuscular Research Institute, University of Western Australia, QE II Medical Centre, Nedlands, Australia
    Neuromuscul Disord 9:330-8. 1999
    ..Molecular intervention at dystrophin pre-mRNA splicing has the potential to reduce the severity of a Duchenne mutation to the milder Becker phenotype...
  34. ncbi Loss of myostatin attenuates severity of muscular dystrophy in mdx mice
    Kathryn R Wagner
    Department of Neurology, The Johns Hopkins University, 725 N Wolfe Street, Baltimore, MD 21205, USA
    Ann Neurol 52:832-6. 2002
    ..Mdx mice lacking myostatin were stronger and more muscular than their mdx counterparts. Diaphragm muscle showed less fibrosis and fatty remodeling, suggesting improved muscle regeneration...
  35. ncbi Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy
    J E Brenman
    Department of Physiology, University of California, San Francisco School of Medicine 94143 0444, USA
    Cell 82:743-52. 1995
    ..Aberrant regulation of nNOS may contribute to preferential degeneration of fast-twitch muscle fibers in DMD...
  36. pmc Force and power output of fast and slow skeletal muscles from mdx mice 6-28 months old
    G S Lynch
    Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109 2007, USA
    J Physiol 535:591-600. 2001
    ..For muscles of both strains, normalised force and power decreased approximately 28 % with age, and consequently weakness was more severe in muscles of old mdx than in those of old control mice...
  37. ncbi Satellite cells from dystrophic (mdx) mice display accelerated differentiation in primary cultures and in isolated myofibers
    Zipora Yablonka-Reuveni
    Department of Biological Structure, School of Medicine, University of Washington, Seattle, Washington, USA
    Dev Dyn 235:203-12. 2006
    ..Furthermore, the study demonstrated that FDB myofibers are an excellent model of the in vivo state of muscle, as they accurately represented the dystrophic phenotype...
  38. pmc Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation
    Chang Hao Cui
    Department of Reproductive Biology and Pathology, National Institute for Child Health and Development, Tokyo, 157 8535, Japan
    Mol Biol Cell 18:1586-94. 2007
    ..These results demonstrate that the endometrial progenitor cells and menstrual blood-derived cells can transfer dystrophin into dystrophied myocytes through cell fusion and transdifferentiation in vitro and in vivo...
  39. ncbi Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathology
    Melissa J Spencer
    Department of Pediatrics and UCLA Duchenne Muscular Dystrophy Research Center, University of California, Los Angeles, CA 90095 1606, USA
    Hum Mol Genet 11:2645-55. 2002
    ..These data suggest that calpains play an active role in necrotic processes in dystrophic muscle and that inhibition of calpains might provide a good therapeutic option for treatment of DMD...
  40. ncbi Dosing regimen has a significant impact on the efficiency of morpholino oligomer-induced exon skipping in mdx mice
    Alberto Malerba
    School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, United Kingdom
    Hum Gene Ther 20:955-65. 2009
    ..These results clearly demonstrate the key role of the optimization of dosing regimen for the systemic administration of PMO in patients, and support the clinical feasibility of this approach with naked PMO...
  41. pmc Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy
    Jachinta E Rooney
    Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557, USA
    Proc Natl Acad Sci U S A 106:7991-6. 2009
    ..These findings demonstrate that laminin-111 is a highly potent therapeutic agent for the mdx mouse model of DMD and represents a paradigm for the systemic delivery of extracellular matrix proteins as therapies for genetic diseases...
  42. pmc Intramembrane charge movement and L-type calcium current in skeletal muscle fibers isolated from control and mdx mice
    C Collet
    Laboratoire de Physiologie des Elements Excitables, Universite Claude Bernard, F69622 Villeurbanne, France
    Biophys J 84:251-65. 2003
    ..They may be speculated to result, at least in part, from remodeling of the submembranous cytoskeleton network due to the absence of dystrophin...
  43. ncbi Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse
    Jerry Chan
    Experimental Fetal Medicine Group, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London, United Kingdom
    Stem Cells 25:875-84. 2007
    ..Although the low-level of chimerism achieved is not curative for DMD, this approach may be useful in other severe mesenchymal or enzyme deficiency syndromes, where low-level protein expression may ameliorate disease pathology...
  44. ncbi Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdx mouse muscle
    Bianca L Gebski
    Centre for Neuromuscular and Neurological Disorders, University of Western Australia, 4th Floor, A Block, QE II Medical Centre, Verdun Street, Nedlands, Perth, Western Australia 6009, Australia
    Hum Mol Genet 12:1801-11. 2003
    ..We show enhanced delivery of a morpholino AO, enabling the advantageous properties to be exploited for potentially therapeutic outcomes...
  45. pmc A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel
    Yuko Iwata
    Department of Molecular Physiology, National Cardiovascular Center Research Institute, Osaka, Japan
    J Cell Biol 161:957-67. 2003
    ..The results suggest that GRC is a key player in the pathogenesis of myocyte degeneration caused by dystrophin-glycoprotein complex disruption...
  46. pmc Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy
    Michelle Wehling-Henricks
    Department of Physiological Science, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA90095 1606, USA
    Hum Mol Genet 17:2280-92. 2008
    ....
  47. pmc Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle
    Yvan Torrente
    Stem Cell Laboratory, Department of Neurological Science, Instituto di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, Centro Dino Ferrari, University of Milan, Italy
    J Clin Invest 114:182-95. 2004
    ..As these cells can be isolated from the blood, manipulated in vitro, and delivered through the circulation, they represent a possible tool for future cell therapy applications in DMD disease or other muscular dystrophies...
  48. pmc Duchenne's muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategies
    C A Collins
    Muscle Cell Biology Group, MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London, UK
    Int J Exp Pathol 84:165-72. 2003
    ..It is possible that a successful treatment will eventually be identified through the integration of studies in multiple species differentially suited to addressing particular questions...
  49. pmc Effects of T-lymphocyte depletion on muscle fibrosis in the mdx mouse
    Jamie Morrison
    Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK
    Am J Pathol 166:1701-10. 2005
    ....
  50. ncbi MyoD is required for myogenic stem cell function in adult skeletal muscle
    L A Megeney
    Institute for Molecular Biology and Biotechnology, Cancer Research Group, McMaster University, Hamilton, Ontario, Canada
    Genes Dev 10:1173-83. 1996
    ....
  51. ncbi Effective exon skipping and restoration of dystrophin expression by peptide nucleic acid antisense oligonucleotides in mdx mice
    HaiFang Yin
    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
    Mol Ther 16:38-45. 2008
    ..Our results demonstrate that PNAs have a higher efficiency of exon skipping than 2'O methyl phosphorothioate AOs do, and have a potential use in AO chemistry for antisense therapy of DMD...
  52. ncbi Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibers
    François Xavier Boittin
    Laboratory of Pharmacology, Geneva Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva 4, Switzerland
    J Cell Sci 119:3733-42. 2006
    ..The Ca2+-independent phospholipase A2 pathway therefore appears as an attractive target to reduce excessive Ca2+ influx and subsequent degeneration occurring in dystrophic fibers...
  53. ncbi Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury from acute mechanical stress
    Robert W Grange
    Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 0430, USA
    Am J Physiol Cell Physiol 283:C1090-101. 2002
    ..stretch condition. These data suggest that the sarcolemma of maturing dystrophic EDL muscles are resistant to acute mechanical injury...
  54. pmc Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice
    Elisabeth R Barton
    Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 157:137-48. 2002
    ..These results suggest that a combination of promoting muscle regenerative capacity and preventing muscle necrosis could be an effective treatment for the secondary symptoms caused by the primary loss of dystrophin...
  55. pmc Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles
    Qi Long Lu
    Muscle Cell Biology, Medical Research Council Clinical Science Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
    Proc Natl Acad Sci U S A 102:198-203. 2005
    ..We conclude that a significant therapeutic effect may be achieved by further optimization in dose and regime of administration of antisense oligonucleotide...
  56. pmc Fibrinogen drives dystrophic muscle fibrosis via a TGFbeta/alternative macrophage activation pathway
    Berta Vidal
    Program on Differentiation and Cancer, Center for Genomic Regulation CRG, Pompeu Fabra University UPF, E 08003 Barcelona, Spain
    Genes Dev 22:1747-52. 2008
    ..Fibrinogen, by engaging its alphavbeta3 receptor on fibroblasts, also directly promotes collagen synthesis. These data unveil a profibrotic role of fibrinogen deposition in muscle dystrophy...
  57. ncbi Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology
    Julia Alter
    Muscle Cell Biology, MRC Clinical Science Centre, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
    Nat Med 12:175-7. 2006
    ..Although the level of dystrophin expression achieved varies considerably between muscles, antisense therapy may provide a realistic hope for the treatment of a majority of individuals with DMD...
  58. ncbi Impact of prednisone on TGF-beta1 and collagen in diaphragm muscle from mdx mice
    J V Hartel
    Department of Physical Therapy, Exercise and Nutrition Sciences, 405 Kimball Tower, State University of New York at Buffalo, Buffalo, New York 14214, USA
    Muscle Nerve 24:428-32. 2001
    ..Although prednisone was beneficial in preventing collagen accumulation, it resulted in a higher level of the HP cross-link, presumably by decreasing collagen turnover..
  59. ncbi Running endurance abnormality in mdx mice
    Hajime Hara
    Division of Neurology, Department of Medicine, Showa University, Fujigaoka Hospital, 1 30, Fujigaoka, Aobaku, Yokohamashi 227 0043, Japan
    Muscle Nerve 25:207-11. 2002
    ..This assay is noninvasive, has the advantage of unbiased automatic data collection, and should be useful for quantifying the mdx deficit in therapeutic studies...
  60. ncbi Differential targeting of nNOS and AQP4 to dystrophin-deficient sarcolemma by membrane-directed alpha-dystrobrevin
    Marvin E Adams
    Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA
    J Cell Sci 121:48-54. 2008
    ..Thus, although nNOS and AQP4 both require interaction with the PDZ domain of alpha-syntrophin for sarcolemmal association, their localization is regulated differentially...
  61. ncbi Steroids in Duchenne muscular dystrophy: from clinical trials to genomic research
    Francesco Muntoni
    The Dubowitz Neuromuscular Centre, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK
    Neuromuscul Disord 12:S162-5. 2002
    ....
  62. pmc Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem cell-like properties as the myogenic source
    J R Beauchamp
    Muscle Cell Biology Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom
    J Cell Biol 144:1113-22. 1999
    ..This minority is behaviorally distinct, slowly dividing in tissue culture, but rapidly proliferative after grafting, suggesting a subpopulation with stem cell-like characteristics...
  63. pmc Interleukin-15 administration improves diaphragm muscle pathology and function in dystrophic mdx mice
    Leah J Harcourt
    Department of Physiology, University of Melbourne, Victoria, Australia, 3010
    Am J Pathol 166:1131-41. 2005
    ....
  64. ncbi The molecular regulation of myogenesis
    L A Sabourin
    Institute for Molecular Biology and Biotechnology, MOBIX, McMaster University, Hamilton, Ontario, Canada
    Clin Genet 57:16-25. 2000
    ..This has put forward the hypothesis that these factors also play specific biological roles following muscle injury and repair...
  65. ncbi Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping
    Aurelie Goyenvalle
    Généthon and CNRS UMR 8115, 1, rue de l Internationale, Evry, France
    Science 306:1796-9. 2004
    ..We report the sustained production of functional dystrophin at physiological levels in entire groups of muscles and the correction of the muscular dystrophy...
  66. pmc Long-term self-renewal of postnatal muscle-derived stem cells
    B M Deasy
    Department of Bioengineering, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Mol Biol Cell 16:3323-33. 2005
    ....
  67. pmc Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and enhanced cell death
    Carole Hirn
    Laboratory of Pharmacology, Geneva Lausanne School of Pharmaceutical Sciences, University of Geneva, CH 1211 Geneva 4, Switzerland
    J Gen Physiol 132:199-208. 2008
    ..4 gating properties and increased Na(+) concentrations are strongly correlated with increased cell death in mdx fibers and that both cell death and Na(+) overload can be reversed by 3 nM tetrodotoxin, a specific Na(v)1.4 blocker...
  68. ncbi Cyclic nucleotide phosphodiesterase isozymes expressed in mouse skeletal muscle
    Timothy J Bloom
    Department of Pharmaceutical Sciences, Campbell University School of Pharmacy, P O Box 1090, Buies Creek, NC 27506, USA
    Can J Physiol Pharmacol 80:1132-5. 2002
    ..Total PDE activity was found to be elevated in tissue extracts from a mouse model of Duchenne's muscular dystrophy...
  69. ncbi Progression of kyphosis in mdx mice
    Nicola Laws
    Centre for Biomedical Research, Faculty of Sciences, Univ of Southern Queensland, Toowoomba, QLD, Australia 4350
    J Appl Physiol (1985) 97:1970-7. 2004
    ..05). We conclude that kyphotic index is a useful measure in mdx and other kyphotic mouse strains, and assessment of paralumbar and accessory respiratory muscles enhance understanding of spinal deformity in muscular dystrophy...
  70. ncbi Dystrophin restoration in skeletal, heart and skin arrector pili smooth muscle of mdx mice by ZM2 NP-AON complexes
    A Ferlini
    Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Ferrara, Italy
    Gene Ther 17:432-8. 2010
    ....
  71. ncbi A-utrophin up-regulation in mdx skeletal muscle is independent of regeneration
    Andrew P Weir
    Department of Human Anatomy and Genetics, University of Oxford, South Parks Rd, Oxford, UK
    Neuromuscul Disord 14:19-23. 2004
    ..These results have important implications for future studies aiming to effect therapeutic utrophin up-regulation in Duchenne muscular dystrophy patients...
  72. pmc Changes in mechanosensitive channel gating following mechanical stimulation in skeletal muscle myotubes from the mdx mouse
    Alfredo Franco-Obregón
    Department of Cellular and Molecular Pharmacology, School of Medicine, University of California, San Francisco, CA 94143 0450, USA
    J Physiol 539:391-407. 2002
    ..We discuss possible mechanisms for the changes in MS channel gating in relation to the known cytoskeletal abnormalities of mdx muscle and its possible implications for the pathogenesis of Duchenne dystrophy...
  73. ncbi Differential expression of the skeletal muscle proteome in mdx mice at different ages
    Yue Ge
    Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor 48109 0606, USA
    Electrophoresis 25:2576-85. 2004
    ..Finally, we analyzed alterations of protein expression in mdx mice at one and six months of age to determine how protein expression changes with disease progression...
  74. ncbi In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping
    Hans A Heemskerk
    DMD Genetic Therapy Group, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    J Gene Med 11:257-66. 2009
    ..In vivo studies are mainly performed using 2'-O-methyl phosphorothioate (2OMePS) or morpholino (PMO) AONs. These compounds were never directly compared...
  75. ncbi Micro-dystrophin cDNA ameliorates dystrophic phenotypes when introduced into mdx mice as a transgene
    Miki Sakamoto
    Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 1 1 Ogawa Higashi, Kodaira, Tokyo 187 8502, Japan
    Biochem Biophys Res Commun 293:1265-72. 2002
    ..These data suggest that the rod structure, and its length in particular, is crucial for the function of micro-dystrophin...
  76. ncbi Talin, vinculin and DRP (utrophin) concentrations are increased at mdx myotendinous junctions following onset of necrosis
    D J Law
    Department of Physiological Science, University of California, Los Angeles 90024 1527
    J Cell Sci 107:1477-83. 1994
    ..These findings indicate that mdx mice may compensate in part for the absence of dystrophin by increased expression of other molecules that subsume dystrophin's mechanical function...
  77. ncbi beta-Dystroglycan can be revealed in microsomes from mdx mouse muscle by detergent treatment
    Nicolas Cluchague
    Faculte de Medecine, UMR CNRS 6026, CS 34317, 35043 Rennes Cedex France
    FEBS Lett 572:216-20. 2004
    ..This result shows that, in dystrophin-deficient muscles, beta-dystroglycan is indeed targeted to the plasma membrane but remains inaccessible to classical solubilizing treatments and to antibodies used for immunolocalization...
  78. ncbi The urokinase plasminogen activator: an interesting way to improve myoblast migration following their transplantation
    E el Fahime
    Unité de Recherche en Génétique Humaine, Centre hospitalier de l Universite Laval, Ste Foy, Quebec, G1V 4G2, Canada
    Exp Cell Res 280:169-78. 2002
    ..These results suggest that increasing uPA expression by an appropriate combination of growth factors and ECM components constitutes a possible approach to improving the migration of myogenic cells after transplantation...
  79. pmc Intracellular calcium signals measured with indo-1 in isolated skeletal muscle fibres from control and mdx mice
    C Collet
    Laboratoire de Physiologie des Elements Excitables, CNRS UMR 5578, Universite Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
    J Physiol 520:417-29. 1999
    ..5. Overall results show that mdx skeletal muscle fibres are quite capable of handling [Ca2+]i at rest and in response to membrane depolarizations...
  80. ncbi Effect of injecting primary myoblasts versus putative muscle-derived stem cells on mass and force generation in mdx mice
    Gunhild M Mueller
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Hum Gene Ther 13:1081-90. 2002
    ..This may, in part, explain the failure of cellular therapy to alter the contractile properties of murine dystrophic muscle...
  81. ncbi Enhanced dystrophic progression in mdx mice by exercise and beneficial effects of taurine and insulin-like growth factor-1
    Annamaria De Luca
    Department of Pharmacobiology, Unit of Pharmacology, University of Bari, Bari, Italy
    J Pharmacol Exp Ther 304:453-63. 2003
    ..Taurine > PDN > IGF-1, but not creatine, significantly ameliorated the negative threshold voltage values of the EDL fibers. The results predict a potential benefit of taurine and IGF-1 for treating human dystrophy...
  82. ncbi Alteration in calcium handling at the subcellular level in mdx myotubes
    V Robert
    Department of Biomedical Sciences, CNR Center of Biomembranes, University of Padova, 35131 Padua, Italy
    J Biol Chem 276:4647-51. 2001
    ..Taking into account the key role played by mitochondria Ca(2+) handling in the control of cell death, our data suggest that mitochondria are potential targets of impaired Ca(2+) homeostasis in muscular dystrophy...
  83. ncbi Platelet-derived growth factor and its receptors are related to the progression of human muscular dystrophy: an immunohistochemical study
    Yajuan Zhao
    Department of Pediatrics, Tohoku University School of Medicine, Sendai 980 8574, Japan
    J Pathol 201:149-59. 2003
    ..They also have roles in muscle fibre regeneration and signalling at neuromuscular junctions in both normal and diseased muscle...
  84. ncbi Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings
    John G Quinlan
    Departments of Neurology, University of Cincinnati, 4011 Medical Science Building, 231 Cincinnati, OH 45267 0525, USA
    Neuromuscul Disord 14:491-6. 2004
    ..These results show that the mdx cardiac function is more impaired than was previously thought and shares important clinical features with the cardiomyopathy of Duchenne muscular dystrophy...
  85. pmc Mechanosensitive channel properties and membrane mechanics in mouse dystrophic myotubes
    Thomas M Suchyna
    Department of Physiology and Biophysics, Center for Single Molecule Biophysics, State University New York SUNY at Buffalo, Buffalo, NY 14214, USA
    J Physiol 581:369-87. 2007
    ..Spontaneous Ca2+ transients in mdx mouse cells are sensitive to depolarization and are inhibited by the specific MSC inhibitor GsMTx4, in both the D and L forms...
  86. pmc L-arginine decreases inflammation and modulates the nuclear factor-kappaB/matrix metalloproteinase cascade in mdx muscle fibers
    Karim Hnia
    INSERM ERI 25 Muscle et Pathologies, CHU A de Villeneuve, Université de Montpellier1, EA 4202, 34295 Montpellier Cedex 5, France
    Am J Pathol 172:1509-19. 2008
    ....
  87. ncbi Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse
    Qi Long Lu
    Muscle Cell Biology, MRC Clinical Science Centre, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK
    Nat Med 9:1009-14. 2003
    ..Our data establishes the realistic practicality of an approach that is applicable, in principle, to a majority of cases of severe dystrophinopathy...
  88. ncbi Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies
    R M Grady
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nat Cell Biol 1:215-20. 1999
    ..These results indicate that both signalling and structural functions of the DGC are required for muscle stability, and implicate alpha-dystrobrevin in the former...
  89. ncbi Expression of matrix metalloproteinases 2 and 9 in regenerating skeletal muscle: a study in experimentally injured and mdx muscles
    S Kherif
    Developpement, Pathologie, Régénération du Système Neuromusculaire Institut de Myologie, INSERM U 153, Rue du Mur des Fermiers Généraux, 47, Bd de l Hopital, Paris Cedex 13, FR 75651, France
    Dev Biol 205:158-70. 1999
    ....
  90. ncbi Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances muscle function in Mdx mice
    Sonia Messina
    Department of Neuroscience, Psychiatry and Anaesthesiology, University of Messina, Italy
    Exp Neurol 198:234-41. 2006
    ..Most importantly, these new findings may have clinical implications for the pharmacological treatment of patients with DMD...
  91. ncbi Impact of sarcoglycan complex on mechanical signal transduction in murine skeletal muscle
    Elisabeth R Barton
    Department of Anatomy and Cell Biology, School of Dental Medicine, and Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia 19104, USA
    Am J Physiol Cell Physiol 290:C411-9. 2006
    ..This study provides evidence that the SGs are involved in the transduction of mechanical information in skeletal muscle, potentially unique from the entire DGC...
  92. pmc Heregulin ameliorates the dystrophic phenotype in mdx mice
    Thomas O B Krag
    Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 101:13856-60. 2004
    ....
  93. ncbi Abnormal cardiac morphology, function and energy metabolism in the dystrophic mdx mouse: an MRI and MRS study
    Wen Zhang
    Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Oxford, UK
    J Mol Cell Cardiol 45:754-60. 2008
    ..We conclude that the absence of dystrophin in adult mdx mouse heart, as in the heart of human patient, is associated with right ventricular dilatation, left ventricular diastolic dysfunction and abnormal energy metabolism...
  94. pmc Microutrophin delivery through rAAV6 increases lifespan and improves muscle function in dystrophic dystrophin/utrophin-deficient mice
    Guy L Odom
    Department of Neurology, Senator Paul D Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington School of Medicine, Seattle, Washington, USA
    Mol Ther 16:1539-45. 2008
    ..This approach may hold promise as a treatment option for DMD because it avoids the potential immune responses that are associated with the delivery of exogenous dystrophin...
  95. ncbi Loss of dystrophin causes aberrant mechanotransduction in skeletal muscle fibers
    Ashok Kumar
    Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
    FASEB J 18:102-13. 2004
    ..Our results show that dystrophin is a load-bearing element and its deficiency leads to loss of muscle stiffness and aberrant mechanotransduction in skeletal muscle fibers...
  96. ncbi Myostatin propeptide gene delivery by adeno-associated virus serotype 8 vectors enhances muscle growth and ameliorates dystrophic phenotypes in mdx mice
    Chunping Qiao
    Division of Molecular Pharmaceutics, University of North Carolina School of Pharmacy, Chapel Hill, NC 27599, USA
    Hum Gene Ther 19:241-54. 2008
    ..These results clearly demonstrate the efficacy of AAV8-mediated myostatin propeptide gene delivery in a rodent model of DMD, and warrant further investigation in large animal models and eventually in human patients...
  97. ncbi Targeted inhibition of Ca2+ /calmodulin signaling exacerbates the dystrophic phenotype in mdx mouse muscle
    Joe V Chakkalakal
    Department of Cellular and Molecular Medicine, Centre for Neuromuscular Diseases, Faculty of Medicine, University of Ottawa, Ottawa, Ont, Canada K1H 8M5
    Hum Mol Genet 15:1423-35. 2006
    ..Finally, our results further support the concept that strategies aimed at promoting the slow oxidative myofiber program in muscle may be effective in altering the relentless progression of DMD...
  98. ncbi Regeneration-blocked mdx muscle: in vivo model for testing treatments
    J G Quinlan
    Department of Neurology, University of Cincinnati, Ohio 45237 0525, USA
    Muscle Nerve 20:1016-23. 1997
    ..Regeneration-blocked normal muscle showed stunted growth but neither progressive wasting nor microscopic pathological changes...
  99. ncbi Expression of full-length utrophin prevents muscular dystrophy in mdx mice
    J Tinsley
    Department of Human Anatomy and Genetics, University of Oxford, UK
    Nat Med 4:1441-4. 1998
    ..These results also have important implications for DMD therapies in which utrophin replacement is achieved by delivery using exogenous vectors...
  100. ncbi Passive mechanical properties of maturing extensor digitorum longus are not affected by lack of dystrophin
    Andrew V Wolff
    Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
    Muscle Nerve 34:304-12. 2006
    ..Determining this threshold may have important clinical implications for treatments of muscular dystrophy involving physical activity...
  101. pmc A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice
    M Wehling
    Department of Physiological Science, University of California at Los Angeles School of Medicine, Los Angeles, CA 90095, USA
    J Cell Biol 155:123-31. 2001
    ..Together, these findings indicate that macrophages promote injury of dystrophin-deficient muscle, and the loss of normal levels of NO production by dystrophic muscle exacerbates inflammation and membrane injury in muscular dystrophy...

Research Grants62

  1. MR Monitoring of PTC124 Treatment in DMD
    KRISTA H VANDENBORNE; Fiscal Year: 2010
    ..The availability of a reliable, nondestructive monitoring method that can be routinely and repeatedly implemented in patients will greatly benefit clinical trials in muscle diseases. ..
  2. Role of murine induced pluripotent stem cells on the correction of cardiac and sk
    Diego Fraidenraich; Fiscal Year: 2010
    ..These experiments will help elucidate the molecular mechanisms that the iPS cells may utilize to effect corrections in cardiac and skeletal muscle and will broaden the therapeutic applicability of the iPS cells. ..
  3. Planning a Multicenter Trial of PDE5A Inhibition for Duchenne Muscular Dystrophy
    Ronald G Victor; Fiscal Year: 2012
    ....
  4. Intravenous Protein Therapy for Treatment of Congenital Muscular Dystrophy
    Bradley L Hodges; Fiscal Year: 2010
    ..The end result of our efforts will be an intravenously delivered protein therapy for patients with MCD1A, DMD and LGMD2C-F...
  5. Excitation-contraction Coupling in Normal and Dystrophic Mammalian Muscle
    Julio L Vergara; Fiscal Year: 2013
    ..The results will significantly broaden our understanding of muscle disease mechanisms and will potentially provide therapeutic molecular tools which are deemed necessary for further advances in gene therapy. ..
  6. Generation of Wunen/LPP3-based therapy for muscular dystrophy
    Hannele Ruohola Baker; Fiscal Year: 2010
    ..Ultimately, in the future we wish to test whether manipulating sphingolipid metabolism can serve therapeutic function in muscular dystrophy treatment. ..
  7. Dual AAV Vectors for Duchenne Muscular Dystrophy Therapy
    Dongsheng Duan; Fiscal Year: 2012
    ..Our findings will pave the way to eventually move dual AAV gene therapy to human trials in the future. ..
  8. Targeting fibrocytes in Duchenne muscular dystrophy
    Lan Zhou; Fiscal Year: 2013
    ..Our long-term goal is to utilize the knowledge gained from these studies to develop novel therapies to reduce scar formation and improve muscle function for patients with DMD. ..
  9. Cardiac Dystrophy: Cellular Mechanisms
    NATALIA V SHIROKOVA; Fiscal Year: 2013
    ..With this basic science project we hope to contribute significantly to translational research in the field of cardiac myopathies and to help to bridge the gap from the molecular defect underlying muscular dystrophy to the bedside. ..
  10. Protein Therapeutics for Muscular Dystrophy
    Norio Takizawa; Fiscal Year: 2013
    ..Completion of the safety/toxicology evaluations will provide the final step in preparation for filing of an IND application testing the use of recombinant MG53 in treatment of muscular dystrophy in human patients. ..
  11. Role of ERK1/2 in Neuromuscular Synapses and Myofiber Development in vivo
    Mendell Rimer; Fiscal Year: 2013
    ....
  12. Effect of Satellite Cell Ablation on the Aging Diaphragm
    Esther E Dupont-Versteegden; Fiscal Year: 2013
    ..abstract_text> ..
  13. Golgi-associated NO-cGMP Signaling Defect in Muscular Dystrophy
    Gail D Thomas; Fiscal Year: 2013
    ..In general, the knowledge generated by this project will be relevant to many types of muscle diseases. ..
  14. Signaling Mechanisms of the Dystrophin-Glycoprotein Complex
    Andrea Arnett; Fiscal Year: 2012
    ..We will also evaluate aspects of skeletal muscle biology, including regeneration, satellite cell activation, extracellular matrix organization, and mitochondrial function that may be influenced by the DGC. ..
  15. Modulation of Muscle Regenerationby Growth Factors
    Elisabeth R Barton; Fiscal Year: 2013
    ..The mechanisms underlying their actions are essential to understand so that repair-enhancing therapies based on their functions can be developed. ..
  16. Spectroscopic Probes of the Muscle Cytoskeleton
    David D Thomas; Fiscal Year: 2013
    ..The findings of the proposed research will provide structure-function guidelines for future therapeutic development. ..
  17. TrkB.T1 as a Genetic Disease Modifier of Muscular Dystrophy
    CHRISTOPHER WILLIAM WARD; Fiscal Year: 2010
    ..This study will try to figure out why these two molecules may be possible therapeutic targets. Our goal is to prevent, improve, or restore muscle function in patients with muscular dystrophy. ..
  18. NF-kappaB signaling in dystrophic cardiomyopathy
    Jennifer M Peterson; Fiscal Year: 2013
    ..Understanding the role of NF-?B signaling in the heart is critical for determining if we can target this pathway for therapy to slow disease progression and improve quality of life for patients. ..
  19. Mitochondria and calcium signaling in skeletal muscle
    NATALIA V SHIROKOVA; Fiscal Year: 2012
    ..2). Define how altered ROS/RNS generation affect cellular Ca2+ homeostasis in muscle from MH-susceptible and mdx mice (a mice model of DMD). ..
  20. Treatment of Muscular Dystrophy-associated Dilated Cardiomyopathy with P-188
    Bruce E Markham; Fiscal Year: 2012
    ..If successful, Phrixus would be able to switch from IV to SQ delivery and greatly increase the likelihood of developing a drug capable helping this patient population. ..
  21. Preclinical Testing of Integrin Enhancing Molecules for the Treatment of Muscular
    Dean J Burkin; Fiscal Year: 2011
    ..This study aims to conduct preclinical testing of novel drugs that enhanced 17 integrin expression in muscle to determine if they maybe of therapeutic value to DMD patients. ..
  22. DYSTROPHIN REPLACEMENT IN MDX MICE
    Jeffrey S Chamberlain; Fiscal Year: 2013
    ..The ultimate goal of this work is to develop a clinically relevant treatment for DMD and other diseases of striated muscle. ..
  23. PHYSIOLOGY OF THYROID HORMONE-DEPENDENT GENE EXPRESSION
    PHILIP REED LARSEN; Fiscal Year: 2013
    ..We will also determine whether therapeutic manipulations of deiodinase activities could be used to enhance the treatment of conditions such as traumatic or degenerative muscle injury or the sarcopenia of the elderly. ..
  24. Structure-Function Analysis of Sarcospan
    RACHELLE HOPE CROSBIE-WATSON; Fiscal Year: 2013
    ..We plan to test the physiological properties of these mice and investigate the mechanisms of sarcospan amelioration. ..
  25. High Content Screening for Muscular Dystrophy
    Herman H Vandenburgh; Fiscal Year: 2010
    ..While not a cure for the disease, these new drug therapies are aimed at enhancing quality and longevity of life of the DMD patient. ..
  26. Calcium and oxidative stress in muscular dystrophy
    Rainer Ng; Fiscal Year: 2012
    ..These mutant mdx mice will be valuable additions to current dystrophic mouse models, as they allow investigators to isolate the contribution of specific CaSeq/Antiox pathways to the dystrophic phenotype. ..
  27. NF-kappaBeta Therapy for Duchenne Muscular Dystrophy
    Denis C Guttridge; Fiscal Year: 2012
    ..Results obtained from this proposal may lead to the development of a new treatment option to improve the quality of life and/or survival of DMD patients. ..
  28. Molecular and Cellular Therapies for Muscular Dystrophy
    Stanley C Froehner; Fiscal Year: 2013
    ..The mechanism of NPC1 phenotype amelioration and its applicability to LGMDs will be studied. Two core facilities will serve the participating laboratories. ..
  29. Electrical Impedance Myography in an Animal Model
    Seward B Rutkove; Fiscal Year: 2013
    ..With the successful completion of this research, we will have greatly expanded our tools to effectively apply and interpret EIM in both pre-clinical animal studies and human clinical research. ..
  30. Stretch-Dependent Calcium Signaling in Heart
    WILLIAM JONATHAN LEDERER; Fiscal Year: 2013
    ..Furthermore it will lay the foundation for novel therapies for diverse heart diseases including Duchenne muscular dystrophy. ..
  31. Integrin Alleviation of Muscular Dystrophy
    Dean J Burkin; Fiscal Year: 2012
    ....
  32. Development of Novel Small Molecules for Delaying the Progression of Muscular Dys
    HUGH LEE SWEENEY; Fiscal Year: 2011
    ..Thus, the ultimate goal of this research proposal is to identify, characterize and optimize small molecules that can be used in a clinical setting to treat muscular dystrophy. ..
  33. A new DMD model with a humanized glycome
    PAUL TAYLOR MARTIN; Fiscal Year: 2013
    ....
  34. Phase 2b Study of PTC124 in Duchenne/Becker Muscular Dystrophy (IND 68,431)
    JAY A BARTH; Fiscal Year: 2012
    ....
  35. Glycosyltransferase Therapy for Myopathies
    PAUL TAYLOR MARTIN; Fiscal Year: 2010
    ..Another long-term goal is to develop a novel connection between glycosylation and myostatin signaling that may more broadly impact therapies for muscle aging and disease. ..
  36. A drug-based approach for integrin-mediated alleviation of muscular dystrophy
    Dean J Burkin; Fiscal Year: 2010
    ..This study aims to identify drugs that increase 17 integrin gene expression which may prove to be of therapeutic value to patients that suffer from DMD. ..
  37. Chemical-based membrane sealants for dystrophic muscle
    JOSEPH MARK METZGER; Fiscal Year: 2010
    ..Hypothesis: Infusion of P188 will confer both immediate and long-term beneficial effects to myocardial performance in vivo with the effects being comparatively greater in dystrophin-deficient dogs than in mice. ..
  38. Inhibitors of BMP-1/TLD proteases as novel therapeutics for muscular dystrophy
    Se Jin Lee; Fiscal Year: 2010
    ..The goal of this project is to develop therapeutic agents capable of blocking myostatin activity and promoting muscle growth in patients with muscle degenerative diseases. ..
  39. National Center for Canine Models of Duchenne Muscular Dystrophy (NCDMD)
    Joe N Kornegay; Fiscal Year: 2011
    ..The NCDMD will also provide high quality facilities and services in compliance with GLP standards to support pre-IND applications. ..
  40. Muscular Dystrophy Therapy by Increased Angiogenesis
    Atsushi Asakura; Fiscal Year: 2013
    ..In addition, we will examine whether increased vasculature provided by the administration of an anti-Flt-1 peptide or shRNA for Flt-1 that block Flt-1 function can improve the muscular dystrophic phenotype in mdx and mdx:utrn-/- mice. ..
  41. Genetic modification of aging and diseased striated muscle
    Jeffrey S Chamberlain; Fiscal Year: 2013
    ..These same methods should also be broadly applicable to developing interventions to slow or halt muscle wasting associated with normal aging. ..
  42. Creative biosynthesis mitigates pathogenesis in mdx mice
    Brian S Tseng; Fiscal Year: 2010
    ..Boys with DMD do not make dystrophin and their muscles weaken over time. The mdx mice do not make dystrophin yet they do not become crippled. These studies may offer important clues that could help with new treatments for boys with DMD. ..
  43. Myogenic Potential of Extraocular Muscle Satellite Cells
    Linda K McLoon; Fiscal Year: 2010
    ..If these hypotheses are true, ultimately we hope to exploit this by using identified myogenic precursor cells from EOM as a new source of donor cells in myoblast therapy in mice models of muscle injury and DMD. ..
  44. Examining the Therapeutic Potential of iPS cells in Duchenne Muscular Dystrophy
    Rita C R Perlingeiro; Fiscal Year: 2010
    ..In Aim 3, we will investigate the mechanisms controlling muscle differentiation in human ES cells with the goal to apply this knowledge to future studies involving human iPS cells obtained from patients with Duchenne muscular dystrophy. ..
  45. Intravenous Protein Therapy for the Treatment of Duchenne Muscular Dystrophy
    BRADLEY HODGES; Fiscal Year: 2009
    ..We are investigating a protein therapy that may prevent the breakdown of skeletal and heart muscles of DMD patients and improve their quality of life. ..
  46. Development of biglycan as a therapeutic for Duchenne Muscular Dystrophy
    Justin R Fallon; Fiscal Year: 2011
    ..We have also enlisted consultants who have extensive expertise in the manufacturing, testing and regulatory issues that are unique to biologies. ..
  47. Dystrophin restoration in two animal models of Duchenne Muscular Dystrophy
    LOUISE RODINO; Fiscal Year: 2009
    ..Finally, the optimal AAV serotype carrying micro-dystrophin in the mouse will be perfused into the femoral artery of the golden retriever muscular dystrophy (GRMD) dog (Aim 3). ..
  48. Development of a Read-Through Drug for Duchenne Muscular Dystrophy
    Carmen Bertoni; Fiscal Year: 2013
    ..If RTC13 can be successfully used to restore dystrophin production with resulting clinical benefit, we will begin planning for the clinical trials in human. ..
  49. Wellstone Muscular Dystrophy Center: Children's Nat'l Med Ctr
    Eric Hoffman; Fiscal Year: 2009
    ....
  50. Mechanisms of Force Loss in Injured and Dystrophic Skeletal Muscle
    Richard M Lovering; Fiscal Year: 2013
    ..Results of this critical comparison will be important as we seek more precise and reliable non-invasive measures to follow the temporal progression of the dystrophic process in children, and novel therapies to treat acute muscle injury. ..
  51. Preclinical Trials of NFkappaB Inhibition in the Treatment of Muscular Dystrophy
    C Carlson; Fiscal Year: 2009
    ..The results of the proposed investigations will provide critical information for establishing clinical trials to test drug efficacy in patients with Duchenne and Becker muscular dystrophy. ..
  52. Protection from hearing loss using calpain inhibitors
    Richard Salvi; Fiscal Year: 2004
    ..Protection from noise-induced hearing loss and ototoxicity would address a major health problem. ..
  53. High Content Screening for Muscular Dystrophy
    Herman Vandenburgh; Fiscal Year: 2007
    ..While not a cure for the disease, these new drug therapies are aimed at enhancing quality and longevity of life of the DMD patient. [unreadable] [unreadable] [unreadable] [unreadable]..
  54. ANALYSIS AND MODULATION OF IMMUNITY IN GENE THERAPY
    Paula Clemens; Fiscal Year: 2003
    ....
  55. cGMP Phosphodiesterase Inhibitors in a Mouse Model of Duchenne Muscular Dystrophy
    STANLEY FROEHNER; Fiscal Year: 2009
    ..They may be useful in many different types of muscular dystrophies by improving muscle health and prolonging survival time. ..
  56. Development of Poloxamer-188 for the Treatment of Muscular Dystrophy Associated H
    BRUCE MARKHAM; Fiscal Year: 2009
    ..It may also be used to treat a genetic form of heart failure, seen at high prevalence, in the mothers of boys with MD. ..
  57. A therapeutic approach to muscle wasting by limiting protein breakdown
    JEFFREY BRAULT; Fiscal Year: 2009
    ..Since these muscle atrophies share many common features, our research on therapies and mechanisms of slowing protein breakdown may lead to a viable treatment for these individuals. ..
  58. Immune Tolerence to Transplanted Myoblasts
    David M Rothstein; Fiscal Year: 2010
    ..Moreover, an understanding of the immune response towards dystrophin, expressed at higher levels and in its native form, will be attained. ..
  59. THE ROLE OF BCL-2 IN SKELETAL MUSCLE STEM CELLS
    JANICE DOMINOV; Fiscal Year: 2000
    ..Such information will significantly contribute to our understanding of muscle biology, and may lead to new therapeutic strategies for treatment of muscle disorders, muscle atrophy and better methods for muscle-based gene therapy. ..
  60. PHASE 2 STUDY OF PTC124 AS AN ORAL TREATMENT FOR NONSEN*
    Langdon Miller; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  61. Role of TGF-B1 in Duchenne Muscular Dystrophy
    Lan Zhou; Fiscal Year: 2010
    ..Knowledge gained from these studies may lead to development of a novel therapeutic approach that targets TGF-B1 expression to ameliorate inflammation and fibrosis in patients with DMD. ..
  62. Expressing full-length dystrophin with AAV
    Dongsheng Duan; Fiscal Year: 2009
    ..In this translational project, we propose to develop a novel tri-AAV system to express the full-length dystrophin protein. If successful, this project will lead to a big breakthrough in DMD gene therapy. ..