Ataluren treatment of patients with nonsense mutation dystrophinopathy

Katharine Bushby, Richard Finkel, Brenda Wong, Richard Barohn, Craig Campbell, Giacomo P Comi, Anne M Connolly, John W Day, Kevin M Flanigan, Nathalie Goemans, Kristi J Jones, Eugenio Mercuri, Ros Quinlivan, James B Renfroe, Barry Russman, Monique M Ryan, Mar Tulinius, Thomas Voit, Steven A Moore, H Lee Sweeney, Richard T Abresch, Kim L Coleman, Michelle Eagle, Julaine Florence, Eduard Gappmaier, Allan M Glanzman, Erik Henricson, Jay Barth, Gary L Elfring, Allen Reha, Robert J Spiegel, Michael W O'donnell, Stuart W Peltz, Craig M Mcdonald, PTC124-GD-007-DMD STUDY GROUP, Monique M Ryan, Andrew J Kornberg, Alison Wray, Kate Carroll, Rachel Kennedy, Daniella Villano, Katy de Valle, Kristi J Jones, Kathryn N North, Mark Dexter, Stephanie Wicks, Kristy Rose, Nathalie Goemans, Gunnar Marcel Buyse, Marleen van den Hauwe, Bart Vrijsen, Craig Campbell, Ashrafu Janmohammad, Cheryl Scholtes, Jean K Mah, Caitlin J Wright, Angela Chiu, Lori M Walker, Harvey B Sarnat, Kathryn Selby, Carol King, Lorelyn Meisner, Thomas Voit, Valérie Doppler, Denis De Castro, Valérie Decostre, Brigitte Chabrol, Nicolas Levy, Cécile Halbert, Yann Pereon, Armelle Magot, Julie Perrier, Jean-Yves Mahe, Anne-Sophie Perrau, Raphaëlle Chasserieau, Ulrike Schara, Sören Lutz, Melanie Busse, Adela Della Marina, Thomas Bosbach, Janbernd Kirschner, Angela Stanescu, Annette Pohl, Cornelia Rensing-Zimmerman, Ulrike Eisele, Ina Fetzer, Sibylle Vogt, Enrico Bertini, Adele D'Amico, Annamaria Kofler, Pediatrico Bambino Gesu, Adelina Carlesi, Anna Maria Bonetti, Maria Giulia Gagliardi, Luigino Santecchia, Francesco Emma, Gianluca Bergami, Eugenio Maria Mercuri, Gessica Vasco, Flaviana Bianco, Elena Stacy Mazzone, Marika Pane, Roberto De Sanctis, Giacomo Pietro Comi, Francesca Magri, Valeria Lucchini, Stefania Paola Corti, Maurizio Gualtiero Moggio, Monica Sciacco, Alessandra Govoni, Nereo Bresolin, Yoram Nevo, Talia Dor-Wollman, Adina Bar-Lev, Debbie Krojanker-Yaffe, Elana Weisband, Juan J Vilchez, Nuria Muelas, Teresa Sevilla, Patricia Smeyers, Florencio Calle, María González, Alberto de la Osa, Jaume Colomer, Carlos Ignacio Ortez, Andrés Nascimento, Ana Febrer, Julita Medina, Robert Muni, Mar Tulinius, Brynja Thorarinsdottir, Niklas Darin, Ulrica Sterky, Anna-Karin Kroksmark, Lisa Berglund, Thomas Sejersen, Mia Hovmöller, Erika Trulsson, Agneta Hök, Pernilla Kipping, Katherine M D Bushby, Michela Guglieri, Volker Straub, Anna Sàrközy, Tracey Willis, Michelle Eagle, Anna Mayhew, Michelle McCallum, Linda Smith, Geoff Bell, Francesco Muntoni, Adnan Yousaf Manzur, Stephanie Ann Robb, Marion Main, Maria Ash, Mariacristina Scoto, Sebahattin Cirak, Rosaline Christina Mary Quinlivan, Martin Richard Smith, Rajesh Pandey, Suzanne James, Nick Emery, Lynne Groves, Richa Kulshrestha, Brenda L Wong, James Collins, Michelle McGuire, Ann McCormick, Paula Morehart, Shengyong Hu, Rebeccah Brown, Richard S Finkel, Carsten G Bonnemann, Michele L Yang, Aileen Reghan Foley, Laureen Murphy-Kotzer, Lindsay Dorsey, Timothy Estilow, Allan M Glanzman, Allison Paisley, Sabrina Yum, Teesha Thomas, Karna Smith, Eduard Gappmaier, Mark B Bromberg, Brianna McGerty, Lauren Lahdan Heidarian, Kathryn Swoboda, Victor Gappmaier, John W Day, Peter Issak Karachunski, Marcia Margolis, Cameron Naughton, Karen Kamiri Buser, Joline Dalton, Katherine Dianne Matthews, Carrie M Stephan, Karla Sue Laubenthal, Basil T Darras, Peter B Kang, Susan O Riley, Janet Quigley, Hailly Butler, Julie Parsons, Susan D Apkon, Melissa Gibbons, Terri Carey, Richard J Barohn, Majed J Dasouki, Heather S Anderson, Anne Arthur, Jeffrey Murray Burns, Mazen M Dimachkie, Mamatha Pasnoor, Yunxia Insia Wang, Laura Herbelin, Rosemary Myles, Emma Ciafaloni, Chad Heatwole, Katy Eichinger, Shree Pandya, Anne Connolly, Alan Pestronk, Muhammad Al-Lozi, Glenn Lopate, Paul Golumbek, R Brian Sommerville, Leo Wang, Anna Wojcicka-Mitchell, Andrew Godbey, Betsy Malkus, Jeanine Schierbecker, Catherine Siener, Mei Lu, Matthew Harms, Arun Varadachary, Stanley Iyadurai, Louisa Rojas, Susan T Iannacone, Heather Gilbreath, Chaiyos Khonghatithum, Ruth Merryman, Leslie Nelson, Mariam Andersen, Medrith Greene, Sharon Kern, Douglas M Sproule, Petra Kaufmann, Darryl De Vivo, Vanessa Battista, Andre Constantinescu, Jacqueline Montes, Sally Dunaway, Megan Montgomery, Jonathan Marra, Craig M McDonald, Jay Han, Erik Henricson, Richard Ted Abresch, Nanette Joyce, Erica Goude, Linda Johnson, Alina Nicorici, Michelle Cregan, J Ben Renfroe, Genei Bougher, Theresa Keohane, Barry S Russman, Michael D Sussman, Kirsten Zilke, Eduardo del Rosario, Stephanie-Burns Wechsler, Vern C Juel, Lisa Hobson-Webb, Edward C Smith, Joanne Mackey, Laura Case, Kathleen Ollendick, Katharine Bushby, Richard Finkel, Brenda Wong, Richard Barohn, Craig Campbell, Giacomo P Comi, Anne M Connolly, John W Day, Kevin M Flanigan, Nathalie Goemans, Kristi J Jones, Eugenio Mercuri, Ros Quinlivan, James B Renfroe, Barry Russman, Monique M Ryan, Mar Tulinius, Thomas Voit, Steven A Moore, H Lee Sweeney, Richard T Abresch, Kim L Coleman, Michelle Eagle, Julaine Florence, Eduard Gappmaier, Allan M Glanzman, Erik Henricson, Jay Barth, Gary L Elfring, Allen Reha, Robert J Spiegel, Michael W O'donnell, Stuart W Peltz, Craig M Mcdonald, PTC124-GD-007-DMD STUDY GROUP, Monique M Ryan, Andrew J Kornberg, Alison Wray, Kate Carroll, Rachel Kennedy, Daniella Villano, Katy de Valle, Kristi J Jones, Kathryn N North, Mark Dexter, Stephanie Wicks, Kristy Rose, Nathalie Goemans, Gunnar Marcel Buyse, Marleen van den Hauwe, Bart Vrijsen, Craig Campbell, Ashrafu Janmohammad, Cheryl Scholtes, Jean K Mah, Caitlin J Wright, Angela Chiu, Lori M Walker, Harvey B Sarnat, Kathryn Selby, Carol King, Lorelyn Meisner, Thomas Voit, Valérie Doppler, Denis De Castro, Valérie Decostre, Brigitte Chabrol, Nicolas Levy, Cécile Halbert, Yann Pereon, Armelle Magot, Julie Perrier, Jean-Yves Mahe, Anne-Sophie Perrau, Raphaëlle Chasserieau, Ulrike Schara, Sören Lutz, Melanie Busse, Adela Della Marina, Thomas Bosbach, Janbernd Kirschner, Angela Stanescu, Annette Pohl, Cornelia Rensing-Zimmerman, Ulrike Eisele, Ina Fetzer, Sibylle Vogt, Enrico Bertini, Adele D'Amico, Annamaria Kofler, Pediatrico Bambino Gesu, Adelina Carlesi, Anna Maria Bonetti, Maria Giulia Gagliardi, Luigino Santecchia, Francesco Emma, Gianluca Bergami, Eugenio Maria Mercuri, Gessica Vasco, Flaviana Bianco, Elena Stacy Mazzone, Marika Pane, Roberto De Sanctis, Giacomo Pietro Comi, Francesca Magri, Valeria Lucchini, Stefania Paola Corti, Maurizio Gualtiero Moggio, Monica Sciacco, Alessandra Govoni, Nereo Bresolin, Yoram Nevo, Talia Dor-Wollman, Adina Bar-Lev, Debbie Krojanker-Yaffe, Elana Weisband, Juan J Vilchez, Nuria Muelas, Teresa Sevilla, Patricia Smeyers, Florencio Calle, María González, Alberto de la Osa, Jaume Colomer, Carlos Ignacio Ortez, Andrés Nascimento, Ana Febrer, Julita Medina, Robert Muni, Mar Tulinius, Brynja Thorarinsdottir, Niklas Darin, Ulrica Sterky, Anna-Karin Kroksmark, Lisa Berglund, Thomas Sejersen, Mia Hovmöller, Erika Trulsson, Agneta Hök, Pernilla Kipping, Katherine M D Bushby, Michela Guglieri, Volker Straub, Anna Sàrközy, Tracey Willis, Michelle Eagle, Anna Mayhew, Michelle McCallum, Linda Smith, Geoff Bell, Francesco Muntoni, Adnan Yousaf Manzur, Stephanie Ann Robb, Marion Main, Maria Ash, Mariacristina Scoto, Sebahattin Cirak, Rosaline Christina Mary Quinlivan, Martin Richard Smith, Rajesh Pandey, Suzanne James, Nick Emery, Lynne Groves, Richa Kulshrestha, Brenda L Wong, James Collins, Michelle McGuire, Ann McCormick, Paula Morehart, Shengyong Hu, Rebeccah Brown, Richard S Finkel, Carsten G Bonnemann, Michele L Yang, Aileen Reghan Foley, Laureen Murphy-Kotzer, Lindsay Dorsey, Timothy Estilow, Allan M Glanzman, Allison Paisley, Sabrina Yum, Teesha Thomas, Karna Smith, Eduard Gappmaier, Mark B Bromberg, Brianna McGerty, Lauren Lahdan Heidarian, Kathryn Swoboda, Victor Gappmaier, John W Day, Peter Issak Karachunski, Marcia Margolis, Cameron Naughton, Karen Kamiri Buser, Joline Dalton, Katherine Dianne Matthews, Carrie M Stephan, Karla Sue Laubenthal, Basil T Darras, Peter B Kang, Susan O Riley, Janet Quigley, Hailly Butler, Julie Parsons, Susan D Apkon, Melissa Gibbons, Terri Carey, Richard J Barohn, Majed J Dasouki, Heather S Anderson, Anne Arthur, Jeffrey Murray Burns, Mazen M Dimachkie, Mamatha Pasnoor, Yunxia Insia Wang, Laura Herbelin, Rosemary Myles, Emma Ciafaloni, Chad Heatwole, Katy Eichinger, Shree Pandya, Anne Connolly, Alan Pestronk, Muhammad Al-Lozi, Glenn Lopate, Paul Golumbek, R Brian Sommerville, Leo Wang, Anna Wojcicka-Mitchell, Andrew Godbey, Betsy Malkus, Jeanine Schierbecker, Catherine Siener, Mei Lu, Matthew Harms, Arun Varadachary, Stanley Iyadurai, Louisa Rojas, Susan T Iannacone, Heather Gilbreath, Chaiyos Khonghatithum, Ruth Merryman, Leslie Nelson, Mariam Andersen, Medrith Greene, Sharon Kern, Douglas M Sproule, Petra Kaufmann, Darryl De Vivo, Vanessa Battista, Andre Constantinescu, Jacqueline Montes, Sally Dunaway, Megan Montgomery, Jonathan Marra, Craig M McDonald, Jay Han, Erik Henricson, Richard Ted Abresch, Nanette Joyce, Erica Goude, Linda Johnson, Alina Nicorici, Michelle Cregan, J Ben Renfroe, Genei Bougher, Theresa Keohane, Barry S Russman, Michael D Sussman, Kirsten Zilke, Eduardo del Rosario, Stephanie-Burns Wechsler, Vern C Juel, Lisa Hobson-Webb, Edward C Smith, Joanne Mackey, Laura Case, Kathleen Ollendick

Abstract

Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders.

Methods: Randomized, double-blind, placebo-controlled study; males ≥ 5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48.

Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo.

Conclusions: As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need.

Keywords: Duchenne muscular dystrophy; genetic; nonsense mutation; orphan; pediatric.

Copyright © 2014 Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Change in 6MWD. Mean changes in the ataluren 10, 10, 20 mg/kg and placebo arms were −12.86 and −44.14 meters, respectively, resulting in a difference of 31.28 meters.
Figure 2
Figure 2
Time to persistent ≥10% worsening in 6MWD.
Figure 3
Figure 3
Mean change in 6MWD from baseline to week 48 in the 

Figure 4

Mean change in 6MWD from…

Figure 4

Mean change in 6MWD from baseline to week 48 in the decline-phase subgroup.

Figure 4
Mean change in 6MWD from baseline to week 48 in the decline-phase subgroup.

Figure 5

Mean change in 6MWD by…

Figure 5

Mean change in 6MWD by disease severity.

Figure 5
Mean change in 6MWD by disease severity.

Figure 6

Timed function tests change from…

Figure 6

Timed function tests change from baseline to week 48 in Study 007 overall…

Figure 6
Timed function tests change from baseline to week 48 in Study 007 overall population versus decline-phase subgroup.

Figure 7

Mean change in 6MWD and…

Figure 7

Mean change in 6MWD and timed function tests by concentration.

Figure 7
Mean change in 6MWD and timed function tests by concentration.

Figure 8

Difference in change from baseline…

Figure 8

Difference in change from baseline and statistical significance by concentration. Note: Shaded area…

Figure 8
Difference in change from baseline and statistical significance by concentration. Note: Shaded area represents exposure range for 40 mg/kg/day ataluren.
All figures (8)
Figure 4
Figure 4
Mean change in 6MWD from baseline to week 48 in the decline-phase subgroup.
Figure 5
Figure 5
Mean change in 6MWD by disease severity.
Figure 6
Figure 6
Timed function tests change from baseline to week 48 in Study 007 overall population versus decline-phase subgroup.
Figure 7
Figure 7
Mean change in 6MWD and timed function tests by concentration.
Figure 8
Figure 8
Difference in change from baseline and statistical significance by concentration. Note: Shaded area represents exposure range for 40 mg/kg/day ataluren.

References

    1. Dent KM, Dunn DM, von Niederhausern AC, Aoyagi AT, Kerr L, Bromberg MB. Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A. 2005;134:295–298.
    1. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007;447:87–91.
    1. Du M, Liu X, Welch EM, Hirawat S, Peltz SW, Bedwell DM. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc Natl Acad Sci U S A. 2008;105:2064–2069.
    1. Wang D, Shukla C, Liu X, Schoeb TR, Clarke LA, Bedwell DM. Characterization of an MPS I-H knock-in mouse that carries a nonsense mutation analogous to the human IDUA-W402X mutation. Mol Genet Metab. 2010;99:62–71.
    1. Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W, Al-Dahhak R. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann Neurol. 2010;67:771–780.
    1. Goldmann T, Overlack N, Wolfrum U, Nagel-Wolfrum K. PTC124-mediated translational readthrough of a nonsense mutation causing Usher syndrome type 1C. Hum Gene Ther. 2011;22:537–547.
    1. Sarkar C, Zhang Z, Mukherjee AB. Stop codon read-through with PTC124 induces palmitoyl-protein thioesterase-1 activity, reduces thioester load and suppresses apoptosis in cultured cells from INCL patients. Mol Genet Metab. 2011;104:338–345.
    1. Tan L, Narayan SB, Chen J, Meyers GD, Bennett MJ. PTC124 improves readthrough and increases enzymatic activity of the CPT1A R160X nonsense mutation. J Inherit Metab Dis. 2011;34:443–447.
    1. Buck NE, Wood LR, Hamilton NJ, Bennett MJ, Peters HL. Treatment of a methylmalonyl-CoA mutase stopcodon mutation. Biochem Biophys Res Commun. 2012;427:753–757.
    1. Gonzalez-Hilarion S, Beghyn T, Jia J, Debreuck N, Berte G, Mamchaoui K. Rescue of nonsense mutations by amlexanox in human cells. Orphanet J Rare Dis. 2012;7:58.
    1. Kayali R, Ku JM, Khitrov G, Jung ME, Prikhodko O, Bertoni C. Read-through compound 13 restores dystrophin expression and improves muscle function in the mdx mouse model for Duchenne muscular dystrophy. Hum Molec Genet. 2012;21:4007–4020.
    1. Sanchez-Alcudia R, Perez B, Ugarte M, Desviat LR. Feasibility of nonsense mutation readthrough as a novel therapeutical approach in propionic acidemia. Hum Mutat. 2012;33:973–980.
    1. Goldmann T, Overlack N, Möller F, Belakhov V, van Wyk M, Baasov T. A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation. EMBO Mol Med. 2012;11:1186–1199.
    1. Bartolomeo R, Polishchuk EV, Volpi N, Polishchuk RS, Auricchio A. Pharmacological read-through of nonsense ARSB mutations as a potential therapeutic approach for mucopolysaccharidosis VI. J Inherit Metab Dis. 2013;36:363–371.
    1. Drake KM, Dunmore BJ, McNelly LN, Morrell NW, Aldred MA. Correction of nonsense BMPR2 and SMAD9 mutations by Ataluren in Pulmonary Arterial Hypertension. Am J Respir Cell Mol Biol. 2013;49:403–409.
    1. Du L, Jung ME, Damoiseaux R, Completo G, Fike F, Ku JM. A new series of novel small molecular weight compounds induce readthrough of all three types of nonsense mutations in the ATM gene. Mol Ther. 2013;21:1653–1660.
    1. Zhou Y, Jiang Q, Takahagi S, Shao C, Uitto J. Premature termination codon read-through in the ABCC6 gene: potential treatment for Pseudoxanthoma elasticum. J Invest Dermatol. 2013;133:2672–2677.
    1. Miller JN, Chan CH, Pearce DA. The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis. Hum Mol Genet. 2013;22:2723–2734.
    1. Gregory-Evans CY, Wang X, Wasan KM, Zhao J, Metcalfe AL, Gregory-Evans K. Postnatal manipulation of Pax6 dosage reverses congenital tissue malformation defects. J Clin Invest. 2014;124:111–116.
    1. Yu H, Liu X, Huang J, Zhang Y, Hu R, Pu J. Comparison of read-through effects of aminoglycosides and PTC124 on rescuing nonsense mutations of HERG gene associated with long QT syndrome. Int J Mol Med. 2014;33:729–735.
    1. Lojewski X, Staropoli JF, Biswas-Legrand S, Simas AM, Haliw L, Selig MK. Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway. Hum Mol Genet. 2014;23:2005–2022.
    1. Finkel R, Flanigan K, Wong B, Bönnemann C, Sampson J, Sweeney HL. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation muscular dystrophy. Plos One. 2013;8:e81302.
    1. Kerem E, Hirawat S, Armoni S, Yaakov Y, Shoseyov D, Cohen M. Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial. Lancet. 2008;372:719–727.
    1. Sermet-Gaudelus I, Boeck KD, Casimir GJ, Vermeulen F, Leal T, Mogenet A. Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis. Am J Respir Crit Care Med. 2010;182:1262–1272.
    1. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9:77–93.
    1. McDonald CM, Henricson EK, Abresch RT, Florence JM, Eagle M, Gappmaier E. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. Muscle Nerve. 2013;48:343–356.
    1. McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Elfring GL. The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle Nerve. 2010;41:500–510.
    1. McDonald CM, Henricson EK, Han JJ, Abresch RT, Nicorici A, Atkinson L. The 6-minute walk test in Duchenne/Becker muscular dystrophy: longitudinal observations. Muscle Nerve. 2010;42:966–974.
    1. Varni JW. The PedsQL™ measurement model for the pediatric quality of life inventory. 2007. .
    1. Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S. Safety, tolerability, and pharmacokinetics of PTC124, a non-aminoglycoside, nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. Clin Pharmacol. 2007;47:430–444.
    1. Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase) J Pediatr. 2004;144:581–588.
    1. Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome) Genet Med. 2006;8:465–473. Erratum in: Genet Med 2006;8:599.
    1. Mallinckrodt CH. Recommendations for the primary analysis of continuous endpoints in longitudinal clinical trials. Drug Info J. 2008;42:303–319.
    1. Mallinckrodt CH, Kenward MG. Conceptual considerations regarding endpoints, hypotheses, and analyses for incomplete longitudinal clinical trial data. Drug Info J. 2009;43:449–458.
    1. Geiger R, Strasak A, Treml B, K Gasser, A Kleinsasser, V Fischer. Six-minute walk test in children and adolescents. J Pediatr. 2007;150:395–399. 399.e1–2.
    1. Henricson E, Abresch R, Han JJ, A Nicorici, E GoudeKeller, G Elfring. Percent-predicted 6-minute walk distance in Duchenne muscular dystrophy to account for maturational influences. Version 2. PLoS Curr. 2012;4:RRN1297. [revised 2012 Feb 2];
    1. Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011;77:444–452.
    1. McDonald CM. Physical activity, health impairments, and disability in neuromuscular disease. Am J Phys Med Rehabil. 2002;81((Suppl)):S108–S120.
    1. Vestergaard P, Glerup H, Steffensen BF, Rejnmark L, Rahbek J, Moseklide L. Fracture risk in patients with muscular dystrophy and spinal muscular atrophy. J Rehabil Med. 2001;33:150–155.
    1. Worton RG, Molnar MJ, Brais B, Karpati G. The muscular dystrophies. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular basis of inherited disease. 8. Vol. 4. New York: McGraw-Hill; 2001. pp. 5493–5523.
    1. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166:111–117.
    1. Kierkegaard M, Tollback A. Reliability and feasibility of the six minute walk test in subjects with myotonic dystrophy. Neuromuscul Disord. 2007;17:943–949.
    1. Mazzone E, Martinelli D, Berardinelli A, Messina S, D'Amico A, Vasco G. North Star Ambulatory Assessment, 6-minute walk test and timed items in ambulant boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2010;20:712–716.
    1. Mazzone E, Vasco G, Sormani MP, Torrente Y, Berardinelli A, Messina S. Functional changes in Duchenne muscular dystrophy: a 12-month longitudinal cohort study. Neurology. 2011;77:250–256.
    1. Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, de Bie E. The 6-minute walk test and person-reported outcomes in boys with Duchenne muscular dystrophy and typically developing controls: longitudinal comparisons and clinically-meaningful changes over one year. Plos Curr. 2013;5 pii: ecurrents md.9e17658b007eb79fcd6f723089f79e06. doi: .
    1. Mazzone ES, Pane M, Sormani MP, Scalise R, Berardinelli A, Messina S. 24 month longitudinal data in ambulant boys with Duchenne muscular dystrophy. PLoS One. 2013;8:e52512.
    1. Yilmaz O, Karaduman A, Topaloglu H. Prednisolone therapy in Duchenne muscular dystrophy prolongs ambulation and prevents scoliosis. Eur J Neurol. 2004;11:541–544.
    1. Kinali M, Main M, Eliahoo J, Messina S, Knight RK, Lehovsky J. Predictive factors for the development of scoliosis in Duchenne muscular dystrophy. Eur J Paediatr Neurol. 2007;11:160–166.
    1. McDonald CM, Abresch RT, Carter GT, Fowler WM Jr, Johnson ER, Kilmer DD. Profiles of neuromuscular diseases. Duchenne muscular dystrophy. Am J Phys Med Rehabil. 1995;74((Suppl)):S70–S92.
    1. Beenakker EAC, Maurits NM, Fock JM, Brouwer OF, van der Hoeven JH. Functional ability and muscle force in healthy children and ambulant Duchenne muscular dystrophy patients. Eur J Paediatr Neurol. 2005;9:387–393.
    1. Uchikawa K, Liu M, Hanayama K, Tsuji T, Fujiwara T, Chino N. Functional status and muscle strength in people with Duchenne muscular dystrophy living in the community. J Rehabil Med. 2004;36:124–129.
    1. Li M, Andersson-Lendahl M, Sejersen T, Arner A. Muscle dysfunction and structural defects of dystrophin-null sapje mutant zebrafish larvae are rescued by ataluren treatment. FASEB J. 2014;28:1593–1599.
    1. Burke JF, Mogg AE. Suppression of a nonsense mutation in mammalian cells in vivo by the aminoglycoside antibiotics G-418 and paromomycin. Nucleic Acids Res. 1985;13:6265–6272.
    1. Lai CH, Chun HH, Nahas SA, Mitui M, Gamo KM, Du L. Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci U S A. 2004;101:15676–15681.
    1. Bellais S, Le Goff C, Dagoneau N, Munnich A, Cormier-Daire V. In vitro readthrough of termination codons by gentamycin in the Stüve-Wiedemann Syndrome. Eur J Hum Genet. 2010;18:130–132.
    1. Brown KJ, Marathi R, Fiorillo AA, Ciccimaro EF, Sharma S, Rowlands DS. Accurate quantitation of dystrophin protein in human skeletal muscle using mass spectrometry. J Bioanal Biomed. 2012;S7 pii: 001.
    1. Treat-NMD Neuromuscular Network. Treat-NMD Newsletter. Web site. Treat-NMD. 2010;87:1–3. . Published 2010. Updated October 2010. Accessed December 2012.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa