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The cooperative international neuromuscular research group Duchenne natural history study: Glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures

Authors

  • Erik K. Henricson MPH,

    1. Department of Physical Medicine and Rehabilitation, School of Medicine, University of California, California, USA
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  • R. Ted Abresch MS,

    1. Department of Physical Medicine and Rehabilitation, School of Medicine, University of California, California, USA
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  • Avital Cnaan PhD,

    1. Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA
    2. Departments of Pediatrics, Epidemiology, and Biostatistics, George Washington University, Washington, DC, USA
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  • Fengming Hu MS,

    1. Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA
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  • Tina Duong MPT,

    1. Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA
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  • Adrienne Arrieta MS,

    1. Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA
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  • Jay Han MD,

    1. Department of Physical Medicine and Rehabilitation, School of Medicine, University of California, California, USA
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  • Diana M. Escolar MD,

    1. Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland, USA
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  • Julaine M. Florence DPT,

    1. Department of Neurology, Washington University, St. Louis, Missouri, USA
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  • Paula R. Clemens MD,

    1. Department of Neurology, University of Pittsburgh and Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania, USA
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  • Eric P. Hoffman PhD,

    1. Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA
    2. Department of Integrative Systems Biology, George Washington University, Washington, DC, USA
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  • Craig M. McDonald MD,

    Corresponding author
    • Department of Physical Medicine and Rehabilitation, School of Medicine, University of California, California, USA
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  • the CINRG Investigators

    1. Department of Physical Medicine and Rehabilitation, School of Medicine, University of California, California, USA
    2. Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA
    3. Departments of Pediatrics, Epidemiology, and Biostatistics, George Washington University, Washington, DC, USA
    4. Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland, USA
    5. Department of Neurology, Washington University, St. Louis, Missouri, USA
    6. Department of Neurology, University of Pittsburgh and Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania, USA
    7. Department of Integrative Systems Biology, George Washington University, Washington, DC, USA
    8. Department of Neurology, Sundaram Medical Foundation and Apollo Children's Hospital, Chennai, India
    9. Department of Paediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada
    10. Division of Pediatric Neurology, Alberta Children's Hospital, Calgary, Alberta, Canada
    11. Department of Pediatrics, University of Gothenburg, Queen Silvia Children's Hospital, Göteborg, Sweden
    12. Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia
    13. Neuropediatric Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
    14. Department of Neurology, Instituto de Neurosciencias Fundacion Favaloro, Buenos Aires, Argentina
    15. Departments of Neurology and Physical Medicine & Rehabilitation, Mayo Clinic, Rochester, Minnesota, USA
    16. Department of Neurology, Children's Hospital, Richmond, Virginia, USA
    17. Department of Neurology, University of Tennessee, Memphis, Tennessee, USA
    18. Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia
    19. Division of Neurosciences, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
    20. Department of Neurology, University of Puerto Rico, San Juan, Puerto Rico
    21. Child Neurology and Psychiatry Department, IRCCS C. Mondino, University of Pavia, Italy and Neuromuscular Omnicentre, Fondazione Serena Onlus, Niguarda Ca' Granda Hospital, Milan, Italy
    22. Department of Pediatrics, Neurology and Developmental Neuroscience, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
    23. Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA
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  • Disclosures: The authors take full responsibility for the contents of this work, which do not represent the views of the U.S. Department of Education, the National Institutes of Health (NIH), the Department of Veterans Affairs, or the United States Government. R.T.A. has served as a consultant for PTC Therapeutics, Inc. A.C. serves as a consultant for GlaxoSmithKline. D.M.E. serves on the speakers bureau for and has received funding for travel and speaker honoraria from Athena Diagnostics, Inc.; he also serves as a consultant for Acceleron Pharma, HALO Therapeutics, AVI Biopharma, the Gerson Lehman Group, and Medacorp. J.M.F. serves on a scientific advisory board for Prosensa, serves on the editorial board of Neuromuscular Disorders, and serves/has served as a member of the CINRG Executive Committee and as a consultant for Prosensa, GlaxoSmithKline, Genzyme Corporation, PTC Therapeutics, Inc., and Acceleron Pharma. E.K.H. is a member of the CINRG Executive Committee, has served as a consultant for Genzyme Corporation and PTC Therapeutics, Inc., and has received travel assistance from Parent Project Muscular Dystrophy. E.P.H. has served on advisory committees for AVI BioPharma, Inc., as a consultant with the Gerson Lehman Group, Medacorp, and Lazard Capital, and is cofounder, board member, and shareholder of ReveraGen Biopharma. C.M.M. has served on advisory committees for PTC Therapeutics, Inc., Sarepta Therapeutics, Inc., GlaxoSmithKline, Prosensa, HALO Therapeutics, Shire HGT, and Novartis AG. The remaining authors have no conflicts of interest to disclose.

  • This study was funded by grants from the U.S. Department of Education/NIDRR (H133B031118, H133B090001), the U.S. Department of Defense (W81XWH-09-1-0592), the NIH (UL1RR031988, U54HD053177, UL1RR024992, U54RR026139, 2U54HD053177, G12RR003051, 1R01AR061875, RO1AR062380), and Parent Project Muscular Dystrophy.

  • C.M.M. is the study's principal investigator; E.K.K., R.T.A., A.C., and C.M.M. are study chairs.

Correspondence to: C.M. McDonald; e-mail: cmmcdonald@ucdavis.edu

ABSTRACT

Introduction: Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies. Methods: The Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, ages 2–28 years. A comprehensive battery of measures was obtained. Results: A novel composite functional “milestone” scale scale showed clinically meaningful mobility and upper limb abilities were significantly preserved in GC-treated adolescents/young adults. Manual muscle test (MMT)-based calculations of global strength showed that those patients <10 years of age treated with steroids declined by 0.4±0.39 MMT unit/year, compared with −0.4±0.39 MMT unit/year in historical steroid-naive subjects. Pulmonary function tests (PFTs) were relatively preserved in steroid-treated adolescents. The linearity and magnitude of decline in measures were affected by maturational changes and functional status. Conclusions: In DMD, long-term use of GCs showed reduced strength loss and preserved functional capabilities and PFTs compared with previous natural history studies performed prior to the widespread use of GC therapy. Muscle Nerve, 2013

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