HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A phase I trial of adeno-associated virus serotype 1-γ-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C.

Abstract
γ-Sarcoglycanopathy or limb girdle muscular dystrophy type 2C is an untreatable disease caused by autosomal recessively inherited mutations of the γ-sarcoglycan gene. Nine non-ambulatory patients (two males, seven females, mean age 27 years; range 16-38 years) with del525T homozygous mutation of the γ-sarcoglycan gene and no γ-sarcoglycan immunostaining on muscle biopsy were divided into three equal groups to receive three escalating doses of an adeno-associated virus serotype 1 vector expressing the human γ-sarcoglycan gene under the control of the desmin promoter, by local injection into the extensor carpi radialis muscle. The first group received a single injection of 3 × 10(9) viral genomes in 100 µl, the second group received a single injection of 1.5 × 10(10) viral genomes in 100 µl, and the third group received three simultaneous 100-µl injections at the same site, delivering a total dose of 4.5 × 10(10) viral genomes. No serious adverse effects occurred during 6 months of follow-up. All nine patients became adeno-associated virus serotype 1 seropositive and one developed a cytotoxic response to the adeno-associated virus serotype 1 capsid. Thirty days later, immunohistochemical analysis of injected-muscle biopsy specimens showed γ-sarcoglycan expression in all three patients who received the highest dose (4.7-10.5% positively stained fibres), while real-time polymerase chain reaction detected γ-sarcoglycan messenger RNA. In one patient, γ-sarcoglycan protein was detected by western blot. For two other patients who received the low and intermediate doses, discrete levels of γ-sarcoglycan expression (<1% positively stained fibres) were also detectable. Expression of γ-sarcoglycan protein can be induced in patients with limb girdle muscular dystrophy type 2C by adeno-associated virus serotype 1 gene transfer, with no serious adverse effects.
AuthorsSerge Herson, Faycal Hentati, Aude Rigolet, Anthony Behin, Norma B Romero, France Leturcq, Pascal Laforêt, Thierry Maisonobe, Rim Amouri, Hafedh Haddad, Muriel Audit, Marie Montus, Carole Masurier, Bernard Gjata, Christophe Georger, Mustapha Cheraï, Pierre Carlier, Jean-Yves Hogrel, Ariane Herson, Yves Allenbach, François M Lemoine, David Klatzmann, H Lee Sweeney, Richard C Mulligan, Bruno Eymard, Didier Caizergues, Thomas Voït, Olivier Benveniste
JournalBrain : a journal of neurology (Brain) Vol. 135 Issue Pt 2 Pg. 483-92 (Feb 2012) ISSN: 1460-2156 [Electronic] England
PMID22240777 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Sarcoglycans
Topics
  • Adolescent
  • Adult
  • Dependovirus (genetics, metabolism)
  • Female
  • Follow-Up Studies
  • Gene Transfer Techniques
  • Genetic Therapy (methods)
  • Genetic Vectors
  • Humans
  • Male
  • Muscular Dystrophies, Limb-Girdle (genetics, metabolism, therapy)
  • Sarcoglycans (genetics, metabolism)
  • Treatment Outcome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: