Preclinical evaluation of the efficacy and safety of adeno-associated virus 8-tissue-nonspecific alkaline phosphatase-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.

We previously showed the efficacy of a single injection of a specially designed viral vector to deliver mineral-targeted TNAP into young and adult mice displaying HPP to prevent/ameliorate their bone and dental defects. In this study, the treatment showed dose-dependent improvements, with higher doses fully correcting bone problems in some cases. However, responses varied by sex and age, with some males showing less improvement and more inflammation. These pre-clinical findings will inform the design of clinical trials using gene therapy in early- and late-onset HPP patients.