Hemophilia A and B are
hereditary coagulation disorders that result from functional deficiencies of
factor VIII (FVIII) or
factor IX (FIX), respectively. Current treatment consists of
injections with plasma-derived or recombinant
clotting factors. Despite the significant clinical benefits of
protein replacement
therapies, these do not constitute a cure and patients are still at risk of
bleeding. Significant progress has been made recently in the development of gene therapy for
hemophilia. This has been primarily due to the technical improvements of existing vector systems and the development of new gene delivery methods. Therapeutic and sometimes physiologic levels of FVIII and FIX could be achieved in FVIII- and FIX-deficient mice and hemophilic dogs using different types of viral vectors. In these preclinical studies, long-term correction of the
bleeding disorders and in some cases a permanent cure has been realized. However, complications related to the induction of
neutralizing antibodies or viral promoter inactivation often precludes stable phenotypic correction. Several gene therapy phase I clinical trials have been initiated in patients suffering from severe
hemophilia A or B. The results from the extensive pre-clinical studies and the preliminary clinical data are encouraging. It is likely that successful gene therapy for
hemophilia will become a reality at the beginning of this new millennium, serving as the trailblazer for gene therapy of other diseases.