707. Prolonged Survival and Improved Phenotypes of Lethal Hypophosphatasia Model Mice By Adeno-Associated Virus-Mediated Muscle Transduction of Bone-Targeted Alkaline Phosphatase

Muscle directed transduction was demonstrated after the injection of scAAV8-MCK-EGFP. The plasma ALP activity was elevated and sustained at therapeutic level, (>1.0 unit/ml) for at least 3 months of scAAV8-MCK-TNALP-D10 treated Akp2–/– mice. The treated Akp2–/– mice grew well and survived over 3 months with healthy appearance (9/10), while untreated Akp2 −/- mice died within 3 weeks (n=10; P<0.001). Improved mineralization of the knee joints was demonstrated by X-ray images and micro CT analysis. Ectopic calcification under this condition was not detected in the treated mice. These results suggest that rAAV-mediated muscle TNALP-D10 transduction strategy would be promising to treat the severe infantile form of HPP.