GENE THERAPY FOR COAGULATION DISORDERS: CURRENT STATE AND FUTURE PERSPECTIVES

Abstract

Inherited bleeding disorders, particularly hemophilia A and B, represent significant global health challenges affecting approximately 400,000 individuals worldwide. Recent advances in gene therapy have revolutionized treatment paradigms, with multiple adeno-associated virus (AAV)-based therapies demonstrating sustained clotting factor expression following single administration. This review synthesizes current clinical evidence, regulatory approvals, safety profiles, and implementation challenges, while proposing strategic recommendations for resource-limited settings. Clinical trials demonstrate factor level increases from <1% to 5-50% of normal, with 40-70% of recipients achieving zero bleeding episodes. However, significant barriers including pre-existing anti-AAV antibodies (20-60% of candidates), high costs ($2-3 million per patient), manufacturing constraints, and uncertainty about lifelong durability temper enthusiasm. For developing nations, strategic preparation through registry development, molecular diagnostics infrastructure, and international collaboration represents a pragmatic pathway toward eventual implementation.