Hemophilia A: An Ideal Disease for Prenatal Therapy.

Abstract

Hemophilia A (HA) is the most common inherited coagulation defect. Current state-of-the-art treatment consists of frequent administration of prophylactic infusions of coagulation factor VIII (FVIII) protein or bispecific antibodies that replace the cofactor function of FVIIIa to maintain hemostasis. However, these treatments are far from ideal, due to their high cost, the need for lifelong treatment, the fact that they are unavailable to a large percentage of the world's persons with hemophilia A (PWHA), and the high risk of treatment failure due to immune response to the infused FVIII protein. Thus, there is a need for novel treatments, such as those using gene therapy and/or cell transplantation, that can promise long-term correction or permanent cure. In the present review, we discuss the clinical feasibility and unique advantages a prenatal approach to HA treatment could offer, placing special emphasis on a sheep model of HA we developed and on using mesenchymal cells (MSC) as cellular delivery vehicles for the FVIII gene to achieve a single treatment cure for HA prior to birth.