Dystrophin immunity in Duchenne's muscular dystrophy

N Engl J Med. 2010 Oct 7;363(15):1429-37. doi: 10.1056/NEJMoa1000228.


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.).

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / analysis*
  • Autoimmunity
  • Child
  • DNA, Viral / analysis
  • Dependovirus
  • Dystrophin / genetics*
  • Dystrophin / immunology
  • Frameshift Mutation
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Immunity, Cellular*
  • Male
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / immunology
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / immunology*
  • Muscular Dystrophy, Duchenne / therapy
  • Protein Biosynthesis
  • T-Lymphocytes / immunology*
  • Transgenes


  • Autoantibodies
  • DNA, Viral
  • Dystrophin

Associated data

  • ClinicalTrials.gov/NCT00428935