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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4532-4541. Prepublished online as a Blood First Edition Paper on August 20, 2008; DOI 10.1182/blood-2008-01-131417. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-131417v1 112/12/4532    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sun, J. Articles by Monahan, P. E. Search for Related Content PubMed PubMed Citation Articles by Sun, J. Articles by Monahan, P. E. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Intraarticular factor IX protein or gene replacement protects against development of hemophilic synovitis in the absence of circulating factor IX Junjiang Sun1, Narine Hakobyan2,3, Leonard A. Valentino2,3, Brian L. Feldman4, R. Jude Samulski1,5, and Paul E. Monahan1,4,6 1 Gene Therapy Center, School of Medicine, University of North Carolina at Chapel Hill; 2 RUSH Hemophilia and Thrombophilia Center and 3 Department of Pediatrics, Rush University Medical Center, Chicago, IL; and 4 Department of Pediatrics, 5 Department of Pharmacology, and 6 Harold R. Roberts Comprehensive Hemophilia Diagnostic and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill Hemophilic bleeding into joints causes synovial and microvascular proliferation and inflammation (hemophilic synovitis) that contribute to end-stage joint degeneration (hemophilic arthropathy), the major morbidity of hemophilia. New therapies are needed for joint deterioration that progresses despite standard intravenous (IV) clotting factor replacement. To test whether factor IX within the joint space can protect joints from hemophilic synovitis, we established a hemophilia B mouse model of synovitis. Factor IX knockout (FIX–/–) mice received a puncture of the knee joint capsule with a needle to induce hemarthrosis; human factor IX (hFIX) was either injected through the needle into the joint space (intraarticularly) or immediately delivered IV. FIX–/– mice receiving intraarticular FIX protein were protected from synovitis compared with mice receiving same or greater doses of hFIX IV. Next, adeno-associated virus (AAV) gene transfer vectors expressing hFIX were injected into knee joints of FIX–/– mice. Joints treated with 1010 vector genomes (vg)/joint AAV2-, AAV5-, or AAV8-hFIX or 2.5 x 109 vg/joint AAV5-hFIX developed significantly fewer pathologic changes 2 weeks after injury compared with the pathology of control injured contralateral hind limbs. Extravascular factor activity and joint-directed gene transfer may ameliorate hemophilic joint destruction, even in the absence of circulating FIX. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: FIXing bleeding joints Thierry VandenDriessche Blood 2008 112: 4366. [Full Text] [PDF]

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