Abstract |
Hemophilia B is caused by a deficiency of blood clotting factor IX (FIX). Previous studies have shown that the delivery of a recombinant adenoviral vector expressing canine FIX (cFIX) resulted in a complete correction of hemophilia B in FIX-deficient dogs, but that cFIX expression decreased to only about 1-2% of normal levels 3 weeks after treatment. In the present study, therapeutic levels of cFIX expression capable of producing a partial correction of hemophilia B were maintained for at least 6 months after the coadministration of the cFIX-expressing adenovirus and the immunosuppressive agent cyclosporin A (CsA). These findings support a recent report (Yang et al., 1994) that host T-cell-mediated immunity against virally transduced cells is a major contributing factor to the transient nature of adenovirus-mediated gene expression in immunocompetent animals. Although a second administration of the cFIX-expressing adenovirus 6 months after the first infusion had only a minimal effect on plasma FIX levels in a dog that had been continuously treated with CsA, the prolonged expression of the transgene indicates that immunosuppression may be applicable in attaining long-term treatment of clinically relevant disorders.
|
Authors | B Fang, R C Eisensmith, H Wang, M A Kay, R E Cross, C N Landen, G Gordon, D A Bellinger, M S Read, P C Hu |
Journal | Human gene therapy
(Hum Gene Ther)
Vol. 6
Issue 8
Pg. 1039-44
(Aug 1995)
ISSN: 1043-0342 [Print] United States |
PMID | 7578416
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Antibodies, Viral
- Immunosuppressive Agents
- Cyclosporine
- Factor IX
|
Topics |
- Adenoviridae
(genetics, immunology)
- Animals
- Antibodies, Viral
(blood)
- Blood Coagulation
- Cyclosporine
(pharmacology)
- Dogs
- Factor IX
(biosynthesis, genetics)
- Genetic Therapy
(methods)
- Genetic Vectors
(genetics)
- Hemophilia B
(blood, therapy)
- Immunosuppression Therapy
- Immunosuppressive Agents
(pharmacology)
- Neutralization Tests
|