title: An octaguanidine-morpholino oligo conjugate improves muscle function of mdx mice.
abstract: BACKGROUND
  Skeletal muscles of mdx mice lack functional levels of dystrophin due to a mutation in Dmd exon 23. Morpholino antisense oligomers can induce expression of a truncated dystrophin by redirecting splicing to skip processing of exon 23.
  
  
  METHODS
  We tested whether systemic administration of Vivo-Morpholino, an octaguanidine delivery moiety-Morpholino conjugate that targets exon 23 (VMO23), restored function to muscles of mdx mice.
  
  
  RESULTS
  Extensor digitorum longus (EDL) muscles of mdx mice were weaker, less powerful, and showed greater functional deficits after eccentric contractions than normal. VMO23 treatment normalized EDL force and power of mdx mice and eliminated their exaggerated sensitivity to eccentric contractions. Diaphragm muscle strips from mdx mice also produced lower-than-normal force and power, and these variables were restored to normal, or near-normal, levels by VMO23 treatment.
  
  
  CONCLUSIONS
  These results provide a functional basis for continuing development of VMO23 as a treatment for Duchenne muscular dystrophy.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. jwidrick@partners.org
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Widrick
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Choi
authors.forename: Shannon T
authors.initials: ST
authors.lastname: Knuth
authors.forename: Paul A
authors.initials: PA
authors.lastname: Morcos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D019791:Guanidine / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D009119:Muscle Contraction / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*
chemical_list: D016189:Dystrophin; D009025:Morpholines; D019791:Guanidine