Gene Therapy Using Adeno-Associated Virus Serotype 8 Encoding TNAP-D₁₀ Improves the Skeletal and Dentoalveolar Phenotypes in Alpl^-/- Mice.

ABSTRACT: Hypophosphatasia (HPP) is caused by loss-of-function mutations in the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP), whose deficiency results in the accumulation of extracellular inorganic pyrophosphate (PP_i ), a potent mineralization inhibitor. Skeletal and dental hypomineralization characterizes HPP, with disease severity varying from life-threatening perinatal or infantile forms to milder forms that manifest in adulthood or only affect the dentition. Enzyme replacement therapy (ERT) using mineral-targeted recombinant TNAP (Strensiq/asfotase alfa) markedly improves the life span, skeletal phenotype, motor function, and quality of life of patients with HPP, though limitations of ERT include frequent injections due to a short elimination half-life of 2.28

SUBMITTER: Kinoshita Y 

PROVIDER: S-EPMC8446309 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature