Gene Therapy Using Recombinant AAV Type 8 Vector Encoding TNAP-D₁₀ Improves the Skeletal Phenotypes in Murine Models of Osteomalacia.

ABSTRACT: Hypophosphatasia (HPP), caused by loss-of-function mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNAP), is characterized by skeletal and dental hypomineralization that can vary in severity from life-threatening to milder manifestations only in adulthood. PHOSPHO1 deficiency leads to early-onset scoliosis, osteomalacia, and fractures that mimic pseudo-HPP. Asfotase alfa, a life-saving enzyme replacement therapy approved for pediatric-onset HPP, requires subcutaneous injections 3 to 6 times per week. We recently showed that a single injection of an adeno-associated virus vector serotype 8 harboring TNAP-D₁₀ (AAV8-TNAP-D₁₀) effectively prevented skeletal disease and prolonged life in Alpl ^-/- mice phenocopyin

SUBMITTER: Amadeu de Oliveira F 

PROVIDER: S-EPMC9850441 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature