Gene therapy for hemophilia

Hemophilia is a genetically inherited bleeding disorder caused by a deficiency of the blood clotting factors VIII (hemophilia A) or IX (hemophilia B). Hemophiliacs suffer prolonged bleeding which can be life threatening and often leads to chronic disabilities. Current hemophilia treatment involves infusions of plasma-derived or recombinant clotting factor in response to bleeding crises. Prophylactic treatment is not available and current treatments remain problematic. The development of a gene therapy for hemophilia has been under investigation for the past decade. An overview is presented of the initial efforts using retroviral and adenoviral vectors for ex vivo and in vivo gene delivery strategies, respectively. Recent progress in developing FIX and FVIII adeno-associated virus vectors is reviewed. Sustained expression of therapeutic levels of FIX and FVIII have been demonstrated in mice. Phenotypic correction of hemophilia B has been shown in the murine and dog models of disease. A phase I human clinical trial has been initiated involving intramuscular injection of FIX. Prospectsfor hemophilia gene therapy look bright and the hopefor a cure has now moved from the realm of the possible to the probable.