Prospects of gene therapy for hemophilia

Abstract

Hemophilia is an X-linked recessive bleeding disorder caused by mutations in the F8 (hemophilia A) or F9 (hemophilia B) gene. Bleeding in hemophiliacs can be treated with the administration of coagulation factor concentrates, whereas patients with severe bleeding require regular replacement therapy with coagulation factor products throughout their life to prevent joint bleeding. Gene therapy is being developed to cure hemophilia as a one-time treatment. The main strategy of gene therapy for hemophilia is the administration of an adeno-associated virus (AAV) vector carrying functional F8 or F9 cDNA. Several clinical trials using AAV vectors showed the maintenance of the plasma coagulation factor for several years following a one-time treatment. Although gene therapy is an extremely attractive treatment alternative for hemophilia, there are still issues to be resolved, including the treatment of the patients with anti-AAV neutralizing antibodies and liver dysfunction after the administration of a high dose of AAV vectors. Long-term observations on the maintenance of therapeutic efficacy and safety after treatment are also required. Gene therapy for hemophilia is expected to be approved in the next few years, but it is important to carefully discuss the efficacy and safety of gene therapy in clinical practice.