Phase I Study of Dystrophin Plasmid-Based Gene Therapy in Duchenne/Becker Muscular Dystrophy
| Autor: | Norma B. Romero, Serge Braun, Olivier Benveniste, France Leturcq, Jean-Yves Hogrel, Glenn E. Morris, Annie Barois, Bruno Eymard, Christine Payan, Véronique Ortega, Anne-Laure Boch, Lise Lejean, Christine Thioudellet, Brigitte Mourot, Christophe Escot, Aurore Choquel, Dominique Recan, Jean-Claude Kaplan, George Dickson, David Klatzmann, Valérie Molinier-Frenckel, Jean-Gérard Guillet, Patrick Squiban, Serge Herson, Michel Fardeau |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities Time Factors Adolescent Biopsy Genetic enhancement Duchenne muscular dystrophy Genetic Vectors Cohort Studies Dystrophin chemistry.chemical_compound Plasmid Genetics medicine Humans RNA Messenger Vector (molecular biology) Muscular dystrophy Muscle Skeletal Promoter Regions Genetic Molecular Biology Models Genetic biology Reverse Transcriptase Polymerase Chain Reaction Histocompatibility Testing Muscles Gene Transfer Techniques Genetic Therapy Middle Aged medicine.disease Immunohistochemistry Molecular biology Muscular Dystrophy Duchenne chemistry biology.protein Molecular Medicine DNA Plasmids |
| Zdroj: | Human Gene Therapy. 15:1065-1076 |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | Nine 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 microg of DNA or twice, 2 weeks apart, with 600 microg 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|