Phase I Study of Dystrophin Plasmid-Based Gene Therapy in Duchenne/Becker Muscular Dystrophy
2004; Mary Ann Liebert, Inc.; Volume: 15; Issue: 11 Linguagem: Inglês
10.1089/hum.2004.15.1065
ISSN1557-7422
AutoresNorma B. Romero, Serge Braun, Olivier Benveniste, France Leturcq, Jean‐Yves Hogrel, Glenn E. Morris, A Barois, B. Eymard, Christine Payan, Véronique Ortega, Anne‐Laure Boch, Lise Lejean, Christine Thioudellet, Brigitte Mourot, Christophe Escot, Aurore Choquel, Dominique Récan, Jean‐Claude Kaplan, George Dickson, David Klatzmann, Valérie Molinier‐Frenkel, Jean‐Gérard Guillet, Patrick Squiban, S. Herson, Michel Fardeau,
Tópico(s)Virus-based gene therapy research
ResumoNine patients with Duchenne or Becker muscular dystrophy were injected via the radialis muscle with a full-length human dystrophin plasmid, either once with 200 or 600 µg of DNA or twice, 2 weeks apart, with 600 µg of DNA. In the biopsies taken 3 weeks after the initial injection, the vector was detected at the injection site in all patients. Immunohistochemistry and nested reverse transcription-polymerase chain reaction indicated dystrophin expression in six of nine patients. The level of expression was low (up to 6% weak, but complete sarcolemmal dystrophin staining, and up to 26% partial sarcolemmal labeling). No side effects were observed, nor any cellular or humoral anti-dystrophin responses. These results suggest that exogenous dystrophin expression can be obtained in Duchenne/Becker patients after intramuscular transfer of plasmid, without adverse effects, hence paving the way for future developments in gene therapy of hereditary muscular diseases.
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