Dystrophin immunity in Duchenne's muscular dystrophy.

Journal Article (Clinical Trial;Journal Article)

We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne's muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.).

Full Text

Duke Authors

Cited Authors

  • Mendell, JR; Campbell, K; Rodino-Klapac, L; Sahenk, Z; Shilling, C; Lewis, S; Bowles, D; Gray, S; Li, C; Galloway, G; Malik, V; Coley, B; Clark, KR; Li, J; Xiao, X; Samulski, J; McPhee, SW; Samulski, RJ; Walker, CM

Published Date

  • October 7, 2010

Published In

Volume / Issue

  • 363 / 15

Start / End Page

  • 1429 - 1437

PubMed ID

  • 20925545

Pubmed Central ID

  • PMC3014106

Electronic International Standard Serial Number (EISSN)

  • 1533-4406

Digital Object Identifier (DOI)

  • 10.1056/NEJMoa1000228


  • eng

Conference Location

  • United States