Dystrophin Immunity in Duchenne’s Muscular Dystrophy
By J. Mendell, Katherine J. Campbell, L. Rodino-Klapac, Zarife Sahenk, C. Shilling, S. Lewis, D. Bowles, S. Gray, Chengwen Li, G. Galloway and 9 more. New England Journal of Medicine, 2010
615 citations recorded by the source corpus.
SUMMARY 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.)
Subfields: Genetics, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/64c1aacb29ea4cb5eacc7e283ebc953dbffa50f4
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Citations in the corpus
- Immune responses to AAV vectors: overcoming barriers to successful gene therapy. (2013, neutral): “99 In another study of intramuscular gene transfer for a 1 -antitrypsin de fi ciency, 98 vector administration was associated with detection of capsid-speci fi c T-cell reactivity and increase in serum creatine kinase in some subjects at approximately day 30 post vector administration.”
- Immune Responses to Viral Gene Therapy Vectors (2020, background): “Some patients with Duchenne muscular dystrophy may actually have pre-existing T cell immunity because of occasional endogenous dystrophin expression in revertant fibers.(81) Because overexpression of utrophin can partially compensate for lack of dystrophin, AAV vectors expressing this “self-gene” th”
- Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans (2018, positive): “Similarly, there have been rare cases in gene therapy trials in which a patient has pre-existing adaptive immunity to the delivered transgene, resulting in a lack of any therapeutic effect from treatment and an expansion of transgeneproduct-specific T-cells (24).”