Dystrophin immunity in Duchenne's muscular dystrophy.
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.).
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
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