title: Revertant fibres and dystrophin traces in Duchenne muscular dystrophy: implication for clinical trials.
abstract: 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.
authors.affiliation: The Dubowitz Neuromuscular Centre, Institute of Child Health, University College, London, UK.
authors.forename: Virginia
authors.initials: V
authors.lastname: Arechavala-Gomeza
authors.forename: Maria
authors.initials: M
authors.lastname: Kinali
authors.forename: Lucy
authors.initials: L
authors.lastname: Feng
authors.forename: Michela
authors.initials: M
authors.lastname: Guglieri
authors.forename: Geraldine
authors.initials: G
authors.lastname: Edge
authors.forename: Marion
authors.initials: M
authors.lastname: Main
authors.forename: David
authors.initials: D
authors.lastname: Hunt
authors.forename: Jan
authors.initials: J
authors.lastname: Lehovsky
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Morgan
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D001706:Biopsy / Q000379:methods; D002648:Child; D049030:Dystroglycans / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism*; D005260:Female; D006801:Humans; D009043:Motor Activity / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: C483081:DAG1 protein, human; D016189:Dystrophin; D049030:Dystroglycans