Linked Life Data

9614557

Source:http://linkedlifedata.com/resource/pubmed/id/9614557

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-6-22
pubmed:abstractText
Duchenne muscular dystrophy (DMD) and murine X-linked muscular dystrophy (mdx) are both due to absence of the subsarcolemmal protein dystrophin. Recombinant adenovirus vectors (AdV) are considered a promising means for delivering a functional dystrophin gene to muscle. However, the usefulness of AdV for this purpose is limited by vector toxicity as well as immune-mediated elimination of infected fibers. In addition, studies to date of AdV-mediated dystrophin gene transfer have either failed to examine effects on muscle strength or been performed in immunologically immature neonatal animals with little baseline abnormality of force-generating capacity. In the present study, AdV-mediated dystrophin gene transfer was performed in adult mdx mice with pre-existent dystrophic pathology and muscle weakness. The main findings are as follows: (1) acute myofiber toxicity and gene transfer efficiency are both AdV dose-dependent, such that the therapeutic margin of safety is fairly narrow; (2) immunosuppressive therapy (FK506) prevents immune-mediated elimination of dystrophin-positive fibers but not the dose-dependent toxic effects; (3) at the optimal vector dosage and with effective immunosuppression, AdV-mediated dystrophin minigene transfer is capable of alleviating the loss of force-generating capacity as well as histopathological evidence of disease progression normally seen in adult mdx muscles over a 2-month period. These findings have important implications for the eventual application of AdV-mediated dystrophin gene transfer in DMD patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
369-79
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Adenovirus-mediated dystrophin minigene transfer improves muscle strength in adult dystrophic (MDX) mice.
pubmed:affiliation
Respiratory Division, Royal Victoria Hospital, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't