Advances in Gene Therapy for Haemophilia.

Gene therapy provides hope for a cure for patients with haemophilia by establishing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene copy to replace the haemophilic patient's own defective gene. Haemophilia may be considered a 'low hanging fruit' for gene therapy because a small increment in blood factor levels (≥2% of normal) significantly improves the bleeding tendency from severe to moderate, eliminating most spontaneous bleeds. After decades of research, the first trial to provide clear evidence of efficiency after gene transfer in patients with haemophilia B using adeno-associated viral (AAV) vectors was reported by our group in 2011. This has been followed by unprecedented activity in this area with the commencement of 7 new early Phase trials involving over 55 patients with haemophilia A or haemophilia B. These studies have, in large part, generated promising clinical data that lay a strong foundation for gene therapy to move forward rapidly to market authorisation. In this review, we discuss the data from our studies and emerging results from other gene therapy trials in both haemophilia A and B.