Unique strategies for therapeutic gene transfer in haemophilia A and haemophilia BWFH State-of-the-Art Session on Therapeutic Gene Transfer Buenos Aires, Argentina. Haemophilia 2010 Jul;16 Suppl 5(Suppl 5):29-34
Date
07/16/2010Pubmed ID
20590853Pubmed Central ID
PMC5592798DOI
10.1111/j.1365-2516.2010.02290.xScopus ID
2-s2.0-77955030405 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Gene therapy of haemophilia has been initiated through a number of approaches including expression in muscle, liver and omental implanted fibroblasts, or i.v. injection of an expression construct under the control of a ubiquitous promoter. In all these approaches, the goal was to have factor VIII (FVIII) or factor IX (FIX) synthesized so that it restored the levels of the missing protein in blood. The three talks in this session are totally, or at least in part, directed at strategies that may be clinically effective even in the absence of correction of the missing plasma clotting factor, although the haematopoietic stem cell or blood outgrowth endothelial cell therapy could achieve plasma correction as well. Two of the approaches achieve localized coagulation factor expression without necessarily correcting the systemic defect--one is with synthesis of FVIII or FIX within the joint space and the other is with the local release of FVIII (or FIX) by platelets at the site of vascular injury. All of the three approaches have demonstrated efficacy in small animal models and are now the subject of larger animal studies. None has yet to progress to human trials.
Author List
Montgomery RR, Monahan PE, Ozelo MCAuthor
Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Factor IXFactor VIII
Factor X
Gene Transfer Techniques
Genetic Therapy
Hematopoietic Stem Cells
Hemophilia A
Hemophilia B
Humans