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

Neuromuscul Disord. 2010 May;20(5):295-301. doi: 10.1016/j.nmd.2010.03.007. Epub 2010 Apr 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biopsy / methods
  • Child
  • Dystroglycans / metabolism
  • Dystrophin / metabolism*
  • Female
  • Humans
  • Motor Activity / physiology
  • Muscle Fibers, Skeletal / pathology*
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / metabolism*
  • Muscular Dystrophy, Duchenne / pathology*
  • Muscular Dystrophy, Duchenne / physiopathology
  • Time Factors

Substances

  • DAG1 protein, human
  • Dystrophin
  • Dystroglycans