Brief Report: Dystrophin Immunity in Duchenne's Muscular Dystrophy.

被引：455

作者：

Mendell, Jerry R. ^{[2
,3
]}

Campbell, Katherine ^{[1
,3
]}

Rodino-Klapac, Louise ^{[2
,3
]}

Sahenk, Zarife ^{[2
,3
]}

Shilling, Chris ^{[2
]}

Lewis, Sarah ^{[2
]}

Bowles, Dawn ^{[4
]}

Gray, Steven ^{[4
]}

Li, Chengwen ^{[4
]}

Galloway, Gloria ^{[2
]}

Malik, Vinod ^{[2
]}

Coley, Brian ^{[2
]}

Clark, K. Reed ^{[2
]}

Li, Juan ^{[5
]}

Xiao, Xiao ^{[5
]}

Samulski, Jade ^{[6
]}

McPhee, Scott W. ^{[6
]}

Samulski, R. Jude ^{[4
]}

Walker, Christopher M. ^{[1
,3
]}

机构：

[1] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Res Inst, Columbus, OH 43205 USA

[2] Nationwide Childrens Hosp, Ctr Gene Therapy, Res Inst, Columbus, OH 43205 USA

[3] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA

[4] Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC USA

[5] Univ N Carolina, Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC USA

[6] Asklepios BioPharmaceut, Chapel Hill, NC USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 363卷 / 15期

关键词：

GENE-TRANSFER; CONGENITAL AMAUROSIS; MUSCLE; REARRANGEMENTS; DEGENERATION; RESPONSES; THERAPY; HUMANS; TRIAL; MICE;

D O I：

10.1056/NEJMoa1000228

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.).

引用

页码：1429 / 1437

页数：9

共 25 条

[21] AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells [J].

Mingozzi, Federico ;

Meulenberg, Janneke J. ;

Hui, Daniel J. ;

Basner-Tschakarjan, Etiena ;

Hasbrouck, Nicole C. ;

Edmonson, Shyrie A. ;

Hutnick, Natalie A. ;

Betts, Michael R. ;

Kastelein, John J. ;

Stroes, Erik S. ;

High, Katherine A. .

BLOOD, 2009, 114 (10) :2077-2086

[22] Genetic treatments in muscular dystrophies [J].

Muntoni, Francesco ;

Wells, Dominic .

CURRENT OPINION IN NEUROLOGY, 2007, 20 (05) :590-594

[23] Local dystrophin restoration with antisense oligonucleotide PRO051 [J].

van Deutekom, Judith C. ;

Janson, Anneke A. ;

Ginjaar, Ieke B. ;

Frankhuizen, Wendy S. ;

Aartsma-Rus, Annemieke ;

Bremmer-Bout, Mattie ;

den Dunnen, Johan T. ;

Koop, Klaas ;

van der Kooi, Anneke J. ;

Goemans, Nathalie M. ;

de Kimpe, Sjef J. ;

Ekhart, Peter F. ;

Venneker, Edna H. ;

Platenburg, Gerard J. ;

Verschuuren, Jan J. ;

van Ommen, Gert-Jan B. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (26) :2677-2686

[24] Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model [J].

Wang, B ;

Li, J ;

Xiao, X .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (25) :13714-13719

[25]

Wells Dominic J, 2002, Expert Rev Mol Med, V4, P1, DOI 10.1017/S146239940200515X

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