Titre :
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Antisense oligonucleotide exon skipping therapy for DMD : Acte de colloque : 4ème colloque international de Myologie (9-13 mai 2011; Lille (France))
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contenu dans :
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Type de document :
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Article
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Editeur :
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AFM-TELETHON, 2011
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Pages :
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p 24
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Langues:
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Anglais
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Mots-clés :
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ARN messager
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colloque
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dystrophie musculaire de Duchenne
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essai clinique
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fibre musculaire cardiaque
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gène DMD
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injection intraveineuse
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oligonucléotide antisens
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pharmacovigilance
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saut d'exon
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utrophine
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Résumé :
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Antisense oligonucleotides (AOs) are able to modulate the splicing of the dystrophin pre-mRNA to correct the aberrant reading frame resulting from mutations in the dystrophin gene and thereby lead to the production of functional amounts of dystrophin protein in patients with Duchenne muscular dystrophy (DMD). A recent dose escalation systemic delivery clinical trial was undertaken using morpholino phosphorodiamidate (PMO) AOs administered intravenously to patients with DMD, carried out by the UK MDEX Consortium in collaboration with AVI BioPharma. The results demonstrated a good safety profile of the drug, dose-dependent restoration dystrophin protein in skeletal muscle tissue and a reduction in the local muscle inflammation observed. Efforts are also underway to improve delivery and activity of PMO AOs with the discovery of high efficiency peptide delivery systems (so-called PPMOs) and a number have been discovered with utility for low dose, high efficiency dystrophin restoration in skeletal and cardiac muscle tissue. AO-mediated exon skipping therefore shows significant promise as an experimental therapy for DMD.
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