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Review Duchenne Muscular Dystrophy
Advances in Pulmonary Care in Duchenne
Oscar H Mayer, 1 Erik K Henricson, 2 Craig M McDonald 2 and Gunnar M Buyse, 3
on behalf of the Cooperative International Neuromuscular Research Group (CINRG) and the DELOS study group
1. Division of Pulmonology, Children’s Hospital of Philadelphia, Philadelphia, US; 2. Department of Physical Medicine and Rehabilitation, School of
Medicine, University of California, Sacramento, US; 3. Paediatric Neurology, University Hospitals Leuven, Belgium
D uchenne muscular dystrophy (DMD) is a degenerative neuromuscular disease leading to progressive muscle weakness and loss. This
review discusses advances in understanding the natural history of DMD, as well as recent pharmacotherapies. Decline in expiratory and
inspiratory pulmonary function results in ineffective airway clearance, sleep-disordered breathing and nocturnal and daytime respiratory
failure. Routine measures of pulmonary function include forced vital capacity (FVC) and peak expiratory flow (PEF). Both measures follow parallel
trajectories and relentlessly decline, reaching the lower limit of normal of 80% of predicted at early teenage years. Moreover, decline in PEF and FVC
are closely correlated with respiratory complications and clinically relevant thresholds for FVC are defined in standard of care recommendations.
Glucocorticoids (GCs) delay the onset of pulmonary function decline, but once patients have reached the 80% of predicted threshold the decline
of FVC and PEF in GC users and patients not using GCs is comparable. In the successful phase III DELOS trial in DMD patients not using GCs,
the short-chain benzoquinone idebenone (Raxone ® , Santhera Pharmaceuticals, Liestal, Switzerland) has demonstrated statistically significant
and clinically relevant efficacy on expiratory and inspiratory function in patients in the pulmonary function decline stage. These results indicate
that idebenone can modify the natural course of respiratory disease progression, which is relevant in clinical practice where loss of respiratory
function continues to be a predominant cause of early morbidity and mortality in DMD.
Keywords Duchenne muscular dystrophy, glucocorticoids, idebenone, pulmonary function, peak expiratory flow, forced vital capacity
Disclosure: All authors act as scientific consultants and advisors to Santhera Pharmaceuticals (Switzerland). Oscar H Mayer has additional consulting
relationships with Bristol-Myers Squib, Marathon Pharmaceuticals, Catabasis Pharmaceuticals, Sarepta Pharmaceuticals, Fibrogen, Biogen, AveXis and
Hoffman-LaRoche, and is an investigator in the SIDEROS trial. Erik K Henricson is study co-chair of the CINRG Duchenne natural history study and has
served as a scientific consultant for Bristol Myers Squibb, PTC Therapeutics and Genzyme, Inc. He received travel assistance from Parent Project Muscular
Dystrophy (USA). Craig M McDonald is study co-chair of the CINRG Duchenne natural history study and has served as a consultant for PTC, Prosensa,
Sarepta, Eli Lilly, Pfizer, Halo Therapeutics, Cardero and Mitokyne, and serves on external advisory boards related to DMD for PTC and Eli Lilly. Gunnar M
Buyse was investigator for clinical trials in Duchenne muscular dystrophy sponsored by Santhera Pharmaceuticals, Prosensa and GlaxoSmithKline, and is
senior clinical investigator of the Research Foundation Flanders (FWO Vlaanderen, Belgium). He is also the inventor of relevant patent applications.
Acknowledgements: Medical writing assistance was provided by Katrina Mountfort at Touch Medical Media, London and funded by Santhera
Pharmaceuticals. The authors thank Mika Leinonen (Santhera Pharmaceuticals, Switzerland) for statistical analyses and Thomas Meier (Santhera
Pharmaceuticals, Switzerland) for contributing to the manuscript and supporting the preparation of analyses, figures and tables. Santhera Pharmaceuticals
is the sponsor of the DELPHI, DELOS and SIDEROS trials and supported this publication.
Investigators of the Cooperative International Neuromuscular Research Group (CINRG): V Vishwanathan, S Chidambaranathan, W Douglas Biggar, Laura C
McAdam, Jean K Mah, Mar Tulinius, Avital Cnaan, Lauren P Morgenroth, Robert Leshner, Carolina Tesi-Rocha, Mathula Thangarajh, Tina Duong, Andrew
Kornberg, Monique Ryan, Yoram Nevo, Alberto Dubrovsky, Paula R Clemens, Hoda Abdel-Hamid, Anne M Connolly, Alan Pestronk, Jean Teasley, Tulio E
Bertorini, Richard Webster, Hanna Kolski, Nancy Kuntz, Sherilyn Driscoll, John B Bodensteiner, Jose Carlo, Ksenija Gorni, Timothy Lotze, John W Day, Peter
Karachunski, Erik K Henricson, Richard T Abresch and Craig M McDonald (for updated affiliations, see online version at www.ncbi.nlm.nih.gov/
pubmed/28139640). Investigators of the DELOS study group (sorted by country): Austria: G Bernert, F Knipp (Vienna). Belgium: GM Buyse, N Goemans, M Van den Hauwe
(Leuven). France: T Voit, V Doppler, T Gidaro (Paris); J-M Cuisset, S Coopman (Lille). Germany: U Schara, S Lutz (Essen); J Kirschner, S Borell, M Will (Freiburg).
Italy: MG D’Angelo, E Brighina, S Gandossini (Lecco); K Gorni, E Falcier (Milan); L Politano, P D'Ambrosio, A Taglia (Naples). The Netherlands: JJGM
Verschuuren, CSM Straathof (Leiden). Spain: JJ Vílchez Padilla, N Muelas Gómez (Valencia). Sweden: T Sejersen, M Hovmöller (Stockholm). Switzerland: P-Y
Jeannet, C Bloetzer (Lausanne). USA: S Iannaccone, D Castro (Dallas); G Tennekoon, R Finkel, C Bönnemann (Philadelphia); C McDonald, E Henricson, N Joyce
(Sacramento); S Apkon, RC Richardson (Seattle).
Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this
manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use,
distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.
Received: February 7, 2017
Accepted: March 13, 2017
Citation: US Neurology, 2017;13(1):35–41
Corresponding Author: Oscar H Mayer, Division of Pulmonology, The Children's Hospital of Philadelphia, 11309 Colket Center, 3510 Civic Center
Boulevard, Philadelphia, PA 19104, US. E: MAYERO@email.chop.edu
Support: The publication of this article was supported by Santhera Pharmaceuticals. The views and opinions expressed are those of the authors and do
not necessarily reﬂect those of Santhera Pharmaceuticals.
TOU CH MED ICA L MEDIA