Genomes and Genes
inbred mdx mice
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.
Publications307 found, 100 shown here
- Long-term administration of pirfenidone improves cardiac function in mdx miceChristel 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...
- Systemic administration of L-arginine benefits mdx skeletal muscle functionElisabeth 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...
- Expression of dystrophin driven by the 1.35-kb MCK promoter ameliorates muscular dystrophy in fast, but not in slow muscles of transgenic mdx micePatrick 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...
- Improved antisense oligonucleotide induced exon skipping in the mdx mouse model of muscular dystrophyChristopher 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...
- Helper (CD4(+)) and cytotoxic (CD8(+)) T cells promote the pathology of dystrophin-deficient muscleM 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...
- Identification of a novel population of muscle stem cells in mice: potential for muscle regenerationZhuqing 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...
- Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophyR 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...
- Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophyA 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...
- Absence of integrin alpha 7 causes a novel form of muscular dystrophyU Mayer
Max Planck Institute for Biochemistry, Martinsried, Germany
Nat Genet 17:318-23. 1997....
- Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibers detected with Ca2+-activated K+ channelsN 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...
- Anti-TNFalpha (Remicade) therapy protects dystrophic skeletal muscle from necrosisMiranda 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...
- Histological parameters for the quantitative assessment of muscular dystrophy in the mdx-mouseAlexandre 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...
- Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profilingR 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...
- Functional improvement of dystrophic muscle by myostatin blockadeSasha 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....
- In situ measurements of calpain activity in isolated muscle fibres from normal and dystrophin-lacking mdx miceP Gailly
Laboratory of Cell Physiology, Catholic University of Louvain, 1200 Brussels, Belgium
J Physiol 582:1261-75. 2007....
- Reduced necrosis of dystrophic muscle by depletion of host neutrophils, or blocking TNFalpha function with Etanercept in mdx miceStuart 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...
- PTC124 targets genetic disorders caused by nonsense mutationsEllen M Welch
PTC Therapeutics, 100 Corporate Court, South Plainfield, New Jersey 07080, USA
Nature 447:87-91. 2007....
- A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cellsJ 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."..
- Effects of stretch-activated channel blockers on [Ca2+]i and muscle damage in the mdx mouseElla 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...
- Sustained dystrophin expression induced by peptide-conjugated morpholino oligomers in the muscles of mdx miceNatee 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...
- T-cell-dependent fibrosis in the mdx dystrophic mouseJ 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...
- Skeletal muscle repair by adult human mesenchymal stem cells from synovial membraneCosimo 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...
- The role of reactive oxygen species in the hearts of dystrophin-deficient mdx miceIwan 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...
- The action potential-evoked sarcoplasmic reticulum calcium release is impaired in mdx mouse muscle fibresChristopher 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...
- 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+ cellsS 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...
- Differential expression of dystrophin isoforms in strains of mdx mice with different mutationsW 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...
- Leukemia inhibitory factor and interleukin-6 are produced by diseased and regenerating skeletal muscleJ B Kurek
Melbourne Neuromuscular Research Centre, St Vincent s Hospital, Fitzroy, Victoria, Australia
Muscle Nerve 19:1291-301. 1996....
- Massive idiosyncratic exon skipping corrects the nonsense mutation in dystrophic mouse muscle and produces functional revertant fibers by clonal expansionQ 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...
- Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx miceMasashi 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...
- Expansion of revertant fibers in dystrophic mdx muscles reflects activity of muscle precursor cells and serves as an index of muscle regenerationToshifumi 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...
- Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression systemS 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...
- rAAV6-microdystrophin rescues aberrant Golgi complex organization in mdx skeletal musclesJustin 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...
- Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotidesS 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...
- Loss of myostatin attenuates severity of muscular dystrophy in mdx miceKathryn 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...
- Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophyJ 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...
- Force and power output of fast and slow skeletal muscles from mdx mice 6-28 months oldG 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...
- Satellite cells from dystrophic (mdx) mice display accelerated differentiation in primary cultures and in isolated myofibersZipora 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...
- Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiationChang 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...
- Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathologyMelissa 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...
- Dosing regimen has a significant impact on the efficiency of morpholino oligomer-induced exon skipping in mdx miceAlberto 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...
- Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophyJachinta 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...
- Intramembrane charge movement and L-type calcium current in skeletal muscle fibers isolated from control and mdx miceC 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...
- Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouseJerry 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...
- Morpholino antisense oligonucleotide induced dystrophin exon 23 skipping in mdx mouse muscleBianca 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...
- A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channelYuko 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...
- Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophyMichelle 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....
- Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscleYvan 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...
- Duchenne's muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategiesC 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...
- Effects of T-lymphocyte depletion on muscle fibrosis in the mdx mouseJamie Morrison
Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK
Am J Pathol 166:1701-10. 2005....
- MyoD is required for myogenic stem cell function in adult skeletal muscleL A Megeney
Institute for Molecular Biology and Biotechnology, Cancer Research Group, McMaster University, Hamilton, Ontario, Canada
Genes Dev 10:1173-83. 1996....
- Effective exon skipping and restoration of dystrophin expression by peptide nucleic acid antisense oligonucleotides in mdx miceHaiFang 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...
- Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibersFrançois 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...
- Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury from acute mechanical stressRobert 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...
- Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx miceElisabeth 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...
- Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal musclesQi 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...
- Fibrinogen drives dystrophic muscle fibrosis via a TGFbeta/alternative macrophage activation pathwayBerta 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...
- Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathologyJulia 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...
- Impact of prednisone on TGF-beta1 and collagen in diaphragm muscle from mdx miceJ 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..
- Running endurance abnormality in mdx miceHajime 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...
- Differential targeting of nNOS and AQP4 to dystrophin-deficient sarcolemma by membrane-directed alpha-dystrobrevinMarvin 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...
- Steroids in Duchenne muscular dystrophy: from clinical trials to genomic researchFrancesco Muntoni
The Dubowitz Neuromuscular Centre, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK
Neuromuscul Disord 12:S162-5. 2002....
- Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem cell-like properties as the myogenic sourceJ 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...
- Interleukin-15 administration improves diaphragm muscle pathology and function in dystrophic mdx miceLeah J Harcourt
Department of Physiology, University of Melbourne, Victoria, Australia, 3010
Am J Pathol 166:1131-41. 2005....
- The molecular regulation of myogenesisL 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...
- Rescue of dystrophic muscle through U7 snRNA-mediated exon skippingAurelie 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...
- Long-term self-renewal of postnatal muscle-derived stem cellsB M Deasy
Department of Bioengineering, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
Mol Biol Cell 16:3323-33. 2005....
- Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and enhanced cell deathCarole 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...
- Cyclic nucleotide phosphodiesterase isozymes expressed in mouse skeletal muscleTimothy 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...
- Progression of kyphosis in mdx miceNicola 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...
- Dystrophin restoration in skeletal, heart and skin arrector pili smooth muscle of mdx mice by ZM2 NP-AON complexesA Ferlini
Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Ferrara, Italy
Gene Ther 17:432-8. 2010....
- A-utrophin up-regulation in mdx skeletal muscle is independent of regenerationAndrew 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...
- Changes in mechanosensitive channel gating following mechanical stimulation in skeletal muscle myotubes from the mdx mouseAlfredo 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...
- Differential expression of the skeletal muscle proteome in mdx mice at different agesYue 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...
- In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skippingHans 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...
- Micro-dystrophin cDNA ameliorates dystrophic phenotypes when introduced into mdx mice as a transgeneMiki 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...
- Talin, vinculin and DRP (utrophin) concentrations are increased at mdx myotendinous junctions following onset of necrosisD 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...
- beta-Dystroglycan can be revealed in microsomes from mdx mouse muscle by detergent treatmentNicolas 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...
- The urokinase plasminogen activator: an interesting way to improve myoblast migration following their transplantationE 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...
- Intracellular calcium signals measured with indo-1 in isolated skeletal muscle fibres from control and mdx miceC 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...
- Effect of injecting primary myoblasts versus putative muscle-derived stem cells on mass and force generation in mdx miceGunhild 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...
- Enhanced dystrophic progression in mdx mice by exercise and beneficial effects of taurine and insulin-like growth factor-1Annamaria 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...
- Alteration in calcium handling at the subcellular level in mdx myotubesV 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...
- Platelet-derived growth factor and its receptors are related to the progression of human muscular dystrophy: an immunohistochemical studyYajuan 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...
- Evolution of the mdx mouse cardiomyopathy: physiological and morphological findingsJohn 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...
- Mechanosensitive channel properties and membrane mechanics in mouse dystrophic myotubesThomas 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...
- L-arginine decreases inflammation and modulates the nuclear factor-kappaB/matrix metalloproteinase cascade in mdx muscle fibersKarim 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....
- Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouseQi 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...
- Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophiesR 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...
- Expression of matrix metalloproteinases 2 and 9 in regenerating skeletal muscle: a study in experimentally injured and mdx musclesS 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....
- Nuclear factor kappa-B blockade reduces skeletal muscle degeneration and enhances muscle function in Mdx miceSonia 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...
- Impact of sarcoglycan complex on mechanical signal transduction in murine skeletal muscleElisabeth 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...
- Heregulin ameliorates the dystrophic phenotype in mdx miceThomas 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....
- Abnormal cardiac morphology, function and energy metabolism in the dystrophic mdx mouse: an MRI and MRS studyWen 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...
- Microutrophin delivery through rAAV6 increases lifespan and improves muscle function in dystrophic dystrophin/utrophin-deficient miceGuy 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...
- Loss of dystrophin causes aberrant mechanotransduction in skeletal muscle fibersAshok 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...
- Myostatin propeptide gene delivery by adeno-associated virus serotype 8 vectors enhances muscle growth and ameliorates dystrophic phenotypes in mdx miceChunping 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...
- Targeted inhibition of Ca2+ /calmodulin signaling exacerbates the dystrophic phenotype in mdx mouse muscleJoe 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...
- Regeneration-blocked mdx muscle: in vivo model for testing treatmentsJ 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...
- Expression of full-length utrophin prevents muscular dystrophy in mdx miceJ 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...
- Passive mechanical properties of maturing extensor digitorum longus are not affected by lack of dystrophinAndrew 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...
- A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx miceM 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...
- MR Monitoring of PTC124 Treatment in DMDKRISTA 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. ..
- Role of murine induced pluripotent stem cells on the correction of cardiac and skDiego 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. ..
- Planning a Multicenter Trial of PDE5A Inhibition for Duchenne Muscular DystrophyRonald G Victor; Fiscal Year: 2012....
- Intravenous Protein Therapy for Treatment of Congenital Muscular DystrophyBradley 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...
- Excitation-contraction Coupling in Normal and Dystrophic Mammalian MuscleJulio 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. ..
- Generation of Wunen/LPP3-based therapy for muscular dystrophyHannele 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. ..
- Dual AAV Vectors for Duchenne Muscular Dystrophy TherapyDongsheng Duan; Fiscal Year: 2012..Our findings will pave the way to eventually move dual AAV gene therapy to human trials in the future. ..
- Targeting fibrocytes in Duchenne muscular dystrophyLan 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. ..
- Cardiac Dystrophy: Cellular MechanismsNATALIA 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. ..
- Protein Therapeutics for Muscular DystrophyNorio 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. ..
- Role of ERK1/2 in Neuromuscular Synapses and Myofiber Development in vivoMendell Rimer; Fiscal Year: 2013....
- Effect of Satellite Cell Ablation on the Aging DiaphragmEsther E Dupont-Versteegden; Fiscal Year: 2013..abstract_text> ..
- Golgi-associated NO-cGMP Signaling Defect in Muscular DystrophyGail D Thomas; Fiscal Year: 2013..In general, the knowledge generated by this project will be relevant to many types of muscle diseases. ..
- Signaling Mechanisms of the Dystrophin-Glycoprotein ComplexAndrea 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. ..
- Modulation of Muscle Regenerationby Growth FactorsElisabeth 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. ..
- Spectroscopic Probes of the Muscle CytoskeletonDavid D Thomas; Fiscal Year: 2013..The findings of the proposed research will provide structure-function guidelines for future therapeutic development. ..
- TrkB.T1 as a Genetic Disease Modifier of Muscular DystrophyCHRISTOPHER 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. ..
- NF-kappaB signaling in dystrophic cardiomyopathyJennifer 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. ..
- Mitochondria and calcium signaling in skeletal muscleNATALIA 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). ..
- Treatment of Muscular Dystrophy-associated Dilated Cardiomyopathy with P-188Bruce 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. ..
- Preclinical Testing of Integrin Enhancing Molecules for the Treatment of MuscularDean 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. ..
- DYSTROPHIN REPLACEMENT IN MDX MICEJeffrey 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. ..
- PHYSIOLOGY OF THYROID HORMONE-DEPENDENT GENE EXPRESSIONPHILIP 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. ..
- Structure-Function Analysis of SarcospanRACHELLE HOPE CROSBIE-WATSON; Fiscal Year: 2013..We plan to test the physiological properties of these mice and investigate the mechanisms of sarcospan amelioration. ..
- High Content Screening for Muscular DystrophyHerman 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. ..
- Calcium and oxidative stress in muscular dystrophyRainer 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. ..
- NF-kappaBeta Therapy for Duchenne Muscular DystrophyDenis 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. ..
- Molecular and Cellular Therapies for Muscular DystrophyStanley 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. ..
- Electrical Impedance Myography in an Animal ModelSeward 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. ..
- Stretch-Dependent Calcium Signaling in HeartWILLIAM JONATHAN LEDERER; Fiscal Year: 2013..Furthermore it will lay the foundation for novel therapies for diverse heart diseases including Duchenne muscular dystrophy. ..
- Integrin Alleviation of Muscular DystrophyDean J Burkin; Fiscal Year: 2012....
- Development of Novel Small Molecules for Delaying the Progression of Muscular DysHUGH 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. ..
- A new DMD model with a humanized glycomePAUL TAYLOR MARTIN; Fiscal Year: 2013....
- Phase 2b Study of PTC124 in Duchenne/Becker Muscular Dystrophy (IND 68,431)JAY A BARTH; Fiscal Year: 2012....
- Glycosyltransferase Therapy for MyopathiesPAUL 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. ..
- A drug-based approach for integrin-mediated alleviation of muscular dystrophyDean 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. ..
- Chemical-based membrane sealants for dystrophic muscleJOSEPH 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. ..
- Inhibitors of BMP-1/TLD proteases as novel therapeutics for muscular dystrophySe 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. ..
- 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. ..
- Muscular Dystrophy Therapy by Increased AngiogenesisAtsushi 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. ..
- Genetic modification of aging and diseased striated muscleJeffrey 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. ..
- Creative biosynthesis mitigates pathogenesis in mdx miceBrian 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. ..
- Myogenic Potential of Extraocular Muscle Satellite CellsLinda 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. ..
- Examining the Therapeutic Potential of iPS cells in Duchenne Muscular DystrophyRita 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. ..
- Intravenous Protein Therapy for the Treatment of Duchenne Muscular DystrophyBRADLEY 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. ..
- Development of biglycan as a therapeutic for Duchenne Muscular DystrophyJustin 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. ..
- Dystrophin restoration in two animal models of Duchenne Muscular DystrophyLOUISE 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). ..
- Development of a Read-Through Drug for Duchenne Muscular DystrophyCarmen 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. ..
- Wellstone Muscular Dystrophy Center: Children's Nat'l Med CtrEric Hoffman; Fiscal Year: 2009....
- Mechanisms of Force Loss in Injured and Dystrophic Skeletal MuscleRichard 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. ..
- Preclinical Trials of NFkappaB Inhibition in the Treatment of Muscular DystrophyC 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. ..
- Protection from hearing loss using calpain inhibitorsRichard Salvi; Fiscal Year: 2004..Protection from noise-induced hearing loss and ototoxicity would address a major health problem. ..
- High Content Screening for Muscular DystrophyHerman 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]..
- ANALYSIS AND MODULATION OF IMMUNITY IN GENE THERAPYPaula Clemens; Fiscal Year: 2003....
- cGMP Phosphodiesterase Inhibitors in a Mouse Model of Duchenne Muscular DystrophySTANLEY FROEHNER; Fiscal Year: 2009..They may be useful in many different types of muscular dystrophies by improving muscle health and prolonging survival time. ..
- Development of Poloxamer-188 for the Treatment of Muscular Dystrophy Associated HBRUCE 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. ..
- A therapeutic approach to muscle wasting by limiting protein breakdownJEFFREY 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. ..
- Immune Tolerence to Transplanted MyoblastsDavid 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. ..
- THE ROLE OF BCL-2 IN SKELETAL MUSCLE STEM CELLSJANICE 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. ..
- PHASE 2 STUDY OF PTC124 AS AN ORAL TREATMENT FOR NONSEN*Langdon Miller; Fiscal Year: 2007..unreadable] [unreadable]..
- Role of TGF-B1 in Duchenne Muscular DystrophyLan 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. ..
- Expressing full-length dystrophin with AAVDongsheng 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. ..