33.5 Adenovirus-associated virus (AAV) vector-mediated gene transfer in hemophilia B

Nathwani et al ., conducted a clinical investigation for a new gene therapy in patients with the hemophilia B disorder. A single dose of serotype-8-pseudotyped, self-complementary AAV vector containing a codon optimized factor IX transgene (designated as scAAV2/8-LP1-hFIXco) was administered intravenously through a peripheral vein in six patients suffering with severe hemophilia B. The factor IX activity in patients enrolled in this study was measured to be less than 1%. The patients were administered low dose, intermediate dose as well as the high dose of the scAAV2/8-LP1-hFIXco vector without any immunosuppressive drugs. The patients were observed for six to sixteen months.

33.5.1 Results

Expression of factor IX increased by 2 to 11% of the normal levels was observed in all study subjects. Out of the 6 study subjects 4 discontinued factor IX treatment and remained free of spontaneous hemorrhage whereas in the other two the duration between prophylactic injections was increased. The study subject out of the two who were administered the high dose of scAAV2/8-LP1-hFIXco vector, one was observed to develop a transient, asymptomatic elevation of serum aminotransferase levels. This elevation was due to the formation of AAV8-capsid-specific T cells in the peripheral blood. The other study subject was observed to develop a small increment in the liver-enzyme levels the cause of this increment was not deduced.

33.5.2 Conclusions

The administration of scAAV2/8-LP1-hFIXco vector via Peripheral-vein infusion caused an enhanced factor IX transgene expression capable of improving the coagulation in study subjects with the bleeding phenotypic trait along with few side effects.