Revertant fibres and dystrophin traces in Duchenne muscular dystrophy: Implication for clinical trials

被引：63

作者：

Arechavala-Gomeza, Virginia ^{[1
]}

Kinali, Maria ^{[1
,2
]}

Feng, Lucy ^{[1
]}

Guglieri, Michela ^{[3
]}

Edge, Geraldine ^{[4
]}

Main, Marion ^{[5
]}

Hunt, David ^{[6
]}

Lehovsky, Jan ^{[7
]}

Straub, Volker ^{[3
]}

Bushby, Kate ^{[3
]}

Sewry, Caroline A. ^{[1
,8
]}

Morgan, Jennifer E. ^{[1
]}

Muntoni, Francesco ^{[1
]}

机构：

[1] UCL, Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England

[2] Hammersmith Hosp, Dept Pediat, London, England

[3] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England

[4] Royal Natl Orthopaed Hosp, Dept Anaesthet, London W1N 6AD, England

[5] Great Ormond St Hosp Sick Children, Dept Physiotherapy, London, England

[6] St Marys Hosp, Dept Orthopaed, London, England

[7] Royal Natl Orthopaed Hosp, Dept Orthopaed, London W1N 6AD, England

[8] RJAH Orthopaed Hosp, Ctr Inherited Neuromuscular Dis, Oswestry, Shrops, England

来源：

NEUROMUSCULAR DISORDERS | 2010年 / 20卷 / 05期

基金：

英国惠康基金;

关键词：

Duchenne muscular dystrophy; Revertant fibres; Dystrophin expression; SOMATIC REVERSION SUPPRESSION; POSITIVE FIBERS; MDX MICE; FRAMESHIFT DELETIONS; NONSENSE MUTATION; MUSCLE-FIBERS; EXPRESSION; GENE; RESTORATION; CELLS;

D O I：

10.1016/j.nmd.2010.03.007

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Duchenne muscular dystrophy (DMD) is characterised by the absence of dystrophin in muscle biopsies, although residual dystrophin can be present, either as dystrophin-positive (revertant) fibres or traces. As restoration of dystrophin expression is the end point of clinical trials, such residual dystrophin is a key factor in recruitment of patients and may also confound the analysis of dystrophin restoration in treated patients, if, as previously observed in the mdx mouse, revertant fibres increase with age. In 62% of the diagnostic biopsies reports of 65 DMD patients studied, traces or revertants were recorded with no correlation between traces or revertants, the patients' performance, or corticosteroids response. In nine of these patients, there was no increase in traces or revertants in biopsies taken a mean of 8.23 years (5.8-10.4 years) after the original diagnostic biopsy. This information should help in the design and execution of clinical trials focused on dystrophin restoration strategies. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：295 / 301

页数：7

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