Dystrophin immunity in Duchenne's muscular dystrophy

Jerry R. Mendell, Katherine Campbell, Louise Rodino-Klapac, Zarife Sahenk, Chris Shilling, Sarah Lewis, Dawn Bowles, Steven Gray, Chengwen Li, Gloria Galloway, Vinod Malik, Brian Coley, K. Reed Clark, Juan Li, Xiao Xiao, Jade Samulski, Scott W. McPhee, R. Jude Samulski, Christopher M. Walker

Research output: Contribution to journalArticle

350 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1429-1437
Number of pages9
JournalNew England Journal of Medicine
Volume363
Issue number15
DOIs
StatePublished - Oct 7 2010

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Dystrophin immunity in Duchenne's muscular dystrophy'. Together they form a unique fingerprint.

  • Cite this

    Mendell, J. R., Campbell, K., Rodino-Klapac, L., Sahenk, Z., Shilling, C., Lewis, S., Bowles, D., Gray, S., Li, C., Galloway, G., Malik, V., Coley, B., Clark, K. R., Li, J., Xiao, X., Samulski, J., McPhee, S. W., Samulski, R. J., & Walker, C. M. (2010). Dystrophin immunity in Duchenne's muscular dystrophy. New England Journal of Medicine, 363(15), 1429-1437. https://doi.org/10.1056/NEJMoa1000228