Revertant fibres and dystrophin traces in Duchenne muscular dystrophy: implication for clinical trials.
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.
Arechavala-Gomeza
Virginia
V
The Dubowitz Neuromuscular Centre, Institute of Child Health, University College, London, UK.
Kinali
Maria
M
Feng
Lucy
L
Guglieri
Michela
M
Edge
Geraldine
G
Main
Marion
M
Hunt
David
D
Lehovsky
Jan
J
Straub
Volker
V
Bushby
Kate
K
Sewry
Caroline A
CA
Morgan
Jennifer E
JE
Muntoni
Francesco
F
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
C483081:DAG1 protein, human; D016189:Dystrophin; D049030:Dystroglycans