[en] INTRODUCTION: The aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53. MATERIALS AND METHODS: We included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52. RESULTS: The difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (p≤0.001). DISCUSSION: Mutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up. CONCLUSION: Our results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.
Disciplines :
Pediatrics Neurology
Author, co-author :
Coratti, Giorgia
Pane, Marika
Brogna, Claudia
Ricotti, Valeria
Messina, Sonia
D'Amico, Adele
Bruno, Claudio
Vita, Gianluca
Berardinelli, Angela
Mazzone, Elena
Magri, Francesca
Ricci, Federica
Mongini, Tiziana
Battini, Roberta
Bello, Luca
Pegoraro, Elena
Baranello, Giovanni
Previtali, Stefano C.
Politano, Luisa
Comi, Giacomo P.
Sansone, Valeria A.
Donati, Alice
Hogrel, Jean Yves
Straub, Volker
De Lucia, Silvana
Niks, Erik
Servais, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
Mazzone ES, Messina S, Vasco G, Main M, Eagle M, D'Amico A, et al. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscul Disord. 2009; 19(7):458-61. https://doi. org/10.1016/j.nmd.2009.06.368 PMID: 19553120
Scott E, Eagle M, Mayhew A, Freeman J, Main M, Sheehan J, et al. Development of a Functional Assessment Scale for Ambulatory Boys with Duchenne Muscular Dystrophy. Physiother Res Int. 2011. https://doi.org/10.1002/pri.520 PMID: 21954141
Mazzone E, Martinelli D, Berardinelli A, Messina S, D'Amico A, Vasco G, et al. North Star Ambulatory Assessment, 6-minute walk test and timed items in ambulant boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2010; 20(11):712-6. https://doi.org/10.1016/j.nmd.2010.06.014 PMID: 20634072
Ricotti V, Ridout DA, Pane M, Main M, Mayhew A, Mercuri E, et al. The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials. J Neurol Neurosurg Psychiatry. 2016; 87(2):149-55. https://doi.org/10.1136/jnnp-2014-309405 PMID: 25733532
Mazzone ES, Pane M, Sormani MP, Scalise R, Berardinelli A, Messina S, et al. 24 month longitudinal data in ambulant boys with Duchenne muscular dystrophy. PLoS One. 2013; 8(1):e52512. https://doi. org/10.1371/journal.pone.0052512 PMID: 23326337
Ricotti V, Ridout DA, Scott E, Quinlivan R, Robb SA, Manzur AY, et al. Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry. 2013; 84(6):698-705. https://doi.org/10.1136/jnnp-2012-303902 PMID: 23250964
Pane M, Mazzone ES, Sivo S, Sormani MP, Messina S, D'Amico A, et al. Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes. PLoS One. 2014; 9(10): e108205. https://doi.org/10.1371/journal.pone.0108205 PMID: 25271887
Bello L, Morgenroth LP, Gordish-Dressman H, Hoffman EP, McDonald CM, Cirak S, et al. DMD genotypes and loss of ambulation in the CINRG Duchenne Natural History Study. Neurology. 2016; 87 (4):401-9. https://doi.org/10.1212/WNL.0000000000002891 PMID: 27343068
Servais L, Montus M, Guiner CL, Ben Yaou R, Annoussamy M, Moraux A, et al. Non-Ambulant Duchenne Patients Theoretically Treatable by Exon 53 Skipping have Severe Phenotype. J Neuromuscul Dis. 2015; 2(3):269-79. https://doi.org/10.3233/JND-150100 PMID: 27858743
Pane M, Mazzone ES, Sormani MP, Messina S, Vita GL, Fanelli L, et al. 6 minute walk test in Duchenne MD patients with different mutations: 12 month changes. PLoS One. 2014; 9(1):e83400. https://doi.org/ 10.1371/journal.pone.0083400 PMID: 24421885
Alfano LN, Charleston JS, Connolly AM, Cripe L, Donoghue C, Dracker R, et al. Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy. Medicine (Baltimore). 2019; 98(26):e15858. https://doi.org/10.1097/MD.0000000000015858 PMID: 31261494
Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016; 79(2):257-71. https://doi.org/10.1002/ana.24555 PMID: 26573217
Mazzone ES, Coratti G, Sormani MP, Messina S, Pane M, D'Amico A, et al. Timed Rise from Floor as a Predictor of Disease Progression in Duchenne Muscular Dystrophy: An Observational Study. PLoS One. 2016; 11(3):e0151445. https://doi.org/10.1371/journal.pone.0151445 PMID: 26982196
Brogna C, Coratti G, Pane M, Ricotti V, Messina S, D'Amico A, et al. Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and
Pane M, Mazzone ES, Sivo S, Sormani MP, Messina S, A DA, et al. Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes. PLoS One. 2014; 9(10): e108205. https://doi.org/10.1371/journal.pone.0108205 PMID: 25271887
Anthony K, Arechavala-Gomeza V, Ricotti V, Torelli S, Feng L, Janghra N, et al. Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. JAMA Neurol. 2014; 71(1):32-40. https://doi.org/10.1001/jamaneurol.2013.4908 PMID: 24217213
van Vliet L, de Winter CL, van Deutekom JC, van Ommen GJ, Aartsma-Rus A. Assessment of the feasibility of exon 45-55 multiexon skipping for Duchenne muscular dystrophy. BMC Med Genet. 2008; 9:105. https://doi.org/10.1186/1471-2350-9-105 PMID: 19046429
Goemans N, Vanden Hauwe M, Signorovitch J, Swallow E, Song J, Collaborative Trajectory Analysis P. Individualized Prediction of Changes in 6-Minute Walk Distance for Patients with Duchenne Muscular Dystrophy. PLoS One. 2016; 11(10):e0164684. https://doi.org/10.1371/journal.pone.0164684 PMID: 27737016
