Functional changes in Becker muscular dystrophy

Implications for clinical trials in dystrophinopathies

Luca Bello, Paola Campadello, Andrea Barp, Marina Fanin, Claudio Semplicini, Gianni Sorarù, Luca Caumo, Chiara Calore, Corrado Angelini, Elena Pegoraro

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21). Only patients in the "del 45-x" or "other" groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p < 0.001). All measures correlated positively with dystrophin quantity and negatively with age, and were significantly more impaired in the "del 45-x" and "other" groups. After one year, NSAA score decreased significantly (-0.9 ± 1.6, p < 0.001); in the "del 45-x" group, both NSAA (-1.3 ± 1.7, p = 0.001) and 6MWT (-12 ± 31 m, p = 0.059) decreased. We conclude that patients with "del x-51" or "del 48" mutations have mild or asymptomatic BMD, while "del 45-x" mutations cause comparatively severe weakness, and functional deterioration in 1 year. Furthermore, exon 51 skipping could be more effective than exon 45 skipping in Duchenne muscular dystrophy.

Original languageEnglish
Article number32439
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Duchenne Muscular Dystrophy
Exons
Clinical Trials
Dystrophin
Mutation
Longitudinal Studies
Skeletal Muscle

ASJC Scopus subject areas

  • General

Cite this

Bello, L., Campadello, P., Barp, A., Fanin, M., Semplicini, C., Sorarù, G., ... Pegoraro, E. (2016). Functional changes in Becker muscular dystrophy: Implications for clinical trials in dystrophinopathies. Scientific Reports, 6, [32439]. https://doi.org/10.1038/srep32439

Functional changes in Becker muscular dystrophy : Implications for clinical trials in dystrophinopathies. / Bello, Luca; Campadello, Paola; Barp, Andrea; Fanin, Marina; Semplicini, Claudio; Sorarù, Gianni; Caumo, Luca; Calore, Chiara; Angelini, Corrado; Pegoraro, Elena.

In: Scientific Reports, Vol. 6, 32439, 01.09.2016.

Research output: Contribution to journalArticle

Bello, L, Campadello, P, Barp, A, Fanin, M, Semplicini, C, Sorarù, G, Caumo, L, Calore, C, Angelini, C & Pegoraro, E 2016, 'Functional changes in Becker muscular dystrophy: Implications for clinical trials in dystrophinopathies', Scientific Reports, vol. 6, 32439. https://doi.org/10.1038/srep32439
Bello, Luca ; Campadello, Paola ; Barp, Andrea ; Fanin, Marina ; Semplicini, Claudio ; Sorarù, Gianni ; Caumo, Luca ; Calore, Chiara ; Angelini, Corrado ; Pegoraro, Elena. / Functional changes in Becker muscular dystrophy : Implications for clinical trials in dystrophinopathies. In: Scientific Reports. 2016 ; Vol. 6.
@article{6d12a96ceb854843b6296bdda3fbdfe6,
title = "Functional changes in Becker muscular dystrophy: Implications for clinical trials in dystrophinopathies",
abstract = "We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ({"}del 45-x{"}, n = 28) or 51 ({"}del x-51{"}, n = 10); isolated exon 48 deletion ({"}del 48{"}, n = 10); and other mutations (n = 21). Only patients in the {"}del 45-x{"} or {"}other{"} groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p < 0.001). All measures correlated positively with dystrophin quantity and negatively with age, and were significantly more impaired in the {"}del 45-x{"} and {"}other{"} groups. After one year, NSAA score decreased significantly (-0.9 ± 1.6, p < 0.001); in the {"}del 45-x{"} group, both NSAA (-1.3 ± 1.7, p = 0.001) and 6MWT (-12 ± 31 m, p = 0.059) decreased. We conclude that patients with {"}del x-51{"} or {"}del 48{"} mutations have mild or asymptomatic BMD, while {"}del 45-x{"} mutations cause comparatively severe weakness, and functional deterioration in 1 year. Furthermore, exon 51 skipping could be more effective than exon 45 skipping in Duchenne muscular dystrophy.",
author = "Luca Bello and Paola Campadello and Andrea Barp and Marina Fanin and Claudio Semplicini and Gianni Sorar{\`u} and Luca Caumo and Chiara Calore and Corrado Angelini and Elena Pegoraro",
year = "2016",
month = "9",
day = "1",
doi = "10.1038/srep32439",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Functional changes in Becker muscular dystrophy

T2 - Implications for clinical trials in dystrophinopathies

AU - Bello, Luca

AU - Campadello, Paola

AU - Barp, Andrea

AU - Fanin, Marina

AU - Semplicini, Claudio

AU - Sorarù, Gianni

AU - Caumo, Luca

AU - Calore, Chiara

AU - Angelini, Corrado

AU - Pegoraro, Elena

PY - 2016/9/1

Y1 - 2016/9/1

N2 - We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21). Only patients in the "del 45-x" or "other" groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p < 0.001). All measures correlated positively with dystrophin quantity and negatively with age, and were significantly more impaired in the "del 45-x" and "other" groups. After one year, NSAA score decreased significantly (-0.9 ± 1.6, p < 0.001); in the "del 45-x" group, both NSAA (-1.3 ± 1.7, p = 0.001) and 6MWT (-12 ± 31 m, p = 0.059) decreased. We conclude that patients with "del x-51" or "del 48" mutations have mild or asymptomatic BMD, while "del 45-x" mutations cause comparatively severe weakness, and functional deterioration in 1 year. Furthermore, exon 51 skipping could be more effective than exon 45 skipping in Duchenne muscular dystrophy.

AB - We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21). Only patients in the "del 45-x" or "other" groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p < 0.001). All measures correlated positively with dystrophin quantity and negatively with age, and were significantly more impaired in the "del 45-x" and "other" groups. After one year, NSAA score decreased significantly (-0.9 ± 1.6, p < 0.001); in the "del 45-x" group, both NSAA (-1.3 ± 1.7, p = 0.001) and 6MWT (-12 ± 31 m, p = 0.059) decreased. We conclude that patients with "del x-51" or "del 48" mutations have mild or asymptomatic BMD, while "del 45-x" mutations cause comparatively severe weakness, and functional deterioration in 1 year. Furthermore, exon 51 skipping could be more effective than exon 45 skipping in Duchenne muscular dystrophy.

UR - http://www.scopus.com/inward/record.url?scp=84985997710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84985997710&partnerID=8YFLogxK

U2 - 10.1038/srep32439

DO - 10.1038/srep32439

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 32439

ER -