Linked Life Data

9686351

Source:http://linkedlifedata.com/resource/pubmed/id/9686351

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1998-10-8
pubmed:abstractText
Citrullinaemia is an autosomal recessive disorder caused by the deficiency of argininosuccinate synthase. The deficiency of this enzyme results in an interruption in the urea cycle and the inability to dispose of excess ammonia derived from the metabolism of protein. The only treatment for this disorder has been dietary restriction of protein and supplementation with medications allowing for alternative excretion of excess nitrogen. Gene therapy offers the possibility of a long-term cure for disorders like citrullinaemia by expressing the deficient gene in the target organ. We have explored the use of adenoviral vectors as a treatment modality for citrullinaemia in two animal models, a naturally occurring bovine model and a murine model created by molecular mutagenesis. Mice treated with adenoviral vectors expressing argininosuccinate synthase lived significantly longer than untreated animals (11 days vs 1 day; however, the animals did not exhibit normal weight gain during the experiment, indicating that the therapeutic effectiveness of the transducing virus was suboptimal. It is speculated that part of the failure to observe better clinical outcome might be due to the deficiency of arginine. In the bovine model, the use of adenoviral vectors did not result in any change in the clinical condition of the animals or in the level of plasma ammonia. However, the use of 15N isotopic ammonia allowed us to assess the flux of nitrogen through the urea cycle during the experiment. These studies revealed a significant increase in the flux through the urea cycle following administration of adenoviral vectors expressing argininosuccinate synthase. We conclude that the use of adenoviral vectors in the treatment of citrullinaemia is a viable approach to therapy but that it will be necessary to increase the level of transduction and to increase the level of enzyme produced from the recombinant viral vector. Future experiments will be designed to address these issues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0141-8955
pubmed:author
pubmed:issnType
Print
pubmed:volume
21 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
138-50
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9686351-Adenoviruses, Human, pubmed-meshheading:9686351-Amino Acid Metabolism, Inborn Errors, pubmed-meshheading:9686351-Ammonia, pubmed-meshheading:9686351-Animals, pubmed-meshheading:9686351-Arginine, pubmed-meshheading:9686351-Argininosuccinate Synthase, pubmed-meshheading:9686351-Benzoates, pubmed-meshheading:9686351-Benzoic Acid, pubmed-meshheading:9686351-Cattle, pubmed-meshheading:9686351-Citrulline, pubmed-meshheading:9686351-Disease Models, Animal, pubmed-meshheading:9686351-Evaluation Studies as Topic, pubmed-meshheading:9686351-Gene Therapy, pubmed-meshheading:9686351-Gene Transfer Techniques, pubmed-meshheading:9686351-Genetic Vectors, pubmed-meshheading:9686351-Liver, pubmed-meshheading:9686351-Mice, pubmed-meshheading:9686351-Nitrogen, pubmed-meshheading:9686351-Treatment Outcome, pubmed-meshheading:9686351-Urea
pubmed:year
1998
pubmed:articleTitle
Evaluation of gene therapy for citrullinaemia using murine and bovine models.
pubmed:affiliation
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't