Current and Future Approaches to Gene Therapy in Patients with Hemophilia

Hemophilia is an X-chromosome-linked recessive bleeding disorder resulting from a F (factor) 8 gene abnormality in hemophilia A and a F9 gene abnormality in hemophilia B. Current products used to replace FVIII or FIX are effective and safe. Nevertheless, gene therapy offers these patients the possibility of achieving a sustained correction of the coagulation defect for their lifetime. Hemophilia has been considered one of the best candidates for a variety of novel gene therapies due to four main factors. First, it is a monogenic disease involving a single protein. Second, small increments of clotting factor levels (2–3%) have shown to have a substantial reduction in the clinical manifestations of the disease. Third, it is easy to measure the activity of transgene (clotting factor activity) delivery through well-defined coagulation assays and finally, there are excellent animal models available. These four factors make hemophilia an excellent disease to investigate gene therapy. Initial clinical trials examining the safety and efficacy of gene transfer in hemophilia have been completed and have demonstrated that gene therapy is feasible; however, there are some obstacles to overcome prior to clinical application.