These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Intravenous infusion of an antisense oligonucleotide results in exon skipping in muscle dystrophin mRNA of Duchenne muscular dystrophy.
    Author: Takeshima Y, Yagi M, Wada H, Ishibashi K, Nishiyama A, Kakumoto M, Sakaeda T, Saura R, Okumura K, Matsuo M.
    Journal: Pediatr Res; 2006 May; 59(5):690-4. PubMed ID: 16627883.
    Abstract:
    Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease that is characterized by muscle dystrophin deficiency. We report that intravenous (IV) infusion of an antisense oligonucleotide created an in-frame dystrophin mRNA from an out-of-frame DMD mutation (via exon skipping) which led to muscle dystrophin expression. A 10-year-old DMD patient possessing an out-of-frame, exon 20 deletion of the dystrophin gene received a 0.5 mg/kg IV infusion of an antisense 31-mer phosphorothioate oligonucleotide against the splicing enhancer sequence of exon 19. This antisense construct was administered at one-week intervals for 4 wk. No side effects attributable to infusion were observed. Exon 19 skipping appeared in a portion of the dystrophin mRNA in peripheral lymphocytes after the infusion. In a muscle biopsy one week after the final infusion, the novel in-frame mRNA lacking both exons 19 and 20 was identified and found to represent approximately 6% of the total reverse transcription PCR product. Dystrophin was identified histochemically in the sarcolemma of muscle cells after oligonucleotide treatment. These findings demonstrate that phosphorothioate oligonucleotides may be administered safely to children with DMD, and that a simple IV infusion is an effective delivery mechanism for oligonucleotides that lead to exon skipping in DMD skeletal muscles.
    [Abstract] [Full Text] [Related] [New Search]