Nathwani et al, report in the last issue of NEJM the results of a clinical trial consisting of an Adenovirus-Associated Virus (AAV) vectorâ€“mediated gene transfer in Hemophilia B. The cohort consisted of 6 patients who received low, intermediate or high doses of the vector. AAV-mediated expression of Factor IX (FIX) at 2 to 11% of normal levels was observed in all participants and was
roughly dose-dependent. 4 of the 6 discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other 2, the interval between prophylactic injections was increased. The two participants who received the high dose of vector received a short course of glucocorticoid therapy after increase of serum liver-enzyme levels which rapidly normalized aminotransferase
levels. The authors conclude that a single peripheral-vein infusion of the vector resulted in long-term expression of the FIX transgene at therapeutic levels without acute or long-lasting toxicity and is a critical step towards converting the severe bleeding phenotype into a mild form or reverse it completely.
Periklis Makrythanasis, MD, PhD
OMMBID Chapter 173: Hemophilia B: Factor IX Deficiency