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 learn more in small animal models and are now the subject of larger animal studies. None has yet to progress to human trials. Gene therapy of haemophilia has been initiated through a number of approaches including expression in muscle find more [1], liver [2] and

omental implanted fibroblasts [3], i.v. injection of an expression construct under the control of a ubiquitous promoter [4]. The follow summarizes three talks given at the World Federation of Haemophilia Meeting in Buenos Aires, Argentina on gene therapy of hemophilia that emphasize new approaches or strategies for gene therapy of hemophilia. Bleeding-induced joint destruction is the major morbidity complicating factor VIII and factor IX deficiency. Standard and appropriate therapy to maintain the health

of joints requires restoring factor activity throughout the entire circulating blood volume. Although bleeding selleck inhibitor into six joints (knees, ankles and elbows) is estimated to account for 80% of haemarthroses [5], few therapies are directed locally to the joints. Gene therapy has been pioneered for rheumatoid arthritis and osteoarthritis [6–8] diseases, which share many pathological features with bleeding-induced arthropathy [9]; the approaches have primarily sought to modulate inflammatory or angiogenic cytokine expression in the joint space. While multiple gene delivery approaches to achieve systemic correction of haemophilia A and B have been investigated, clinical success has yet to be achieved [2,10–12]. Local therapy directed to joints could potentially address the major complication of haemophilia while circumventing some barriers to systemic expression, for example if the requirement for the total therapeutic protein expression was decreased or if the immune presentation of potentially immunogenic gene delivery vectors or clotting factor differed quantitatively or qualitatively. A series of investigations now have explored the hypothesis that extravascular clotting factor in the joint tissues in haemophilia can contribute to local haemostasis and protection from joint deterioration independently of circulating plasma clotting factor [11,12].