ArticleHuman gene therapy2011
Rescue of severe infantile hypophosphatasia mice by AAV-mediated sustained expression of soluble alkaline phosphatase.
Article in Human gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- 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.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Review
- Raman Spectroscopic Analysis of Molecular Structure and Mechanical Properties of Hypophosphatasia Primary Tooth.Molecules (Basel, Switzerland) · 2024Article
- Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.Journal of the American Dental Association (1939) · 2024Review
- Biomedical applications of solid-binding peptides and proteins.Materials today. Bio · 2023Review
- Gene Therapy Using Recombinant AAV Type 8 Vector Encoding TNAP-DJBMR plus · 2023Article
- Dental manifestation and management of hypophosphatasia.The Japanese dental science review · 2022Review
- Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm.Cells · 2021Review
- Treatment with bone maturation and average lifespan of HPP model mice by AAV8-mediated neonatal gene therapy via single muscle injection.Molecular therapy. Methods & clinical development · 2021Article
- Gene Therapy Using Adeno-Associated Virus Serotype 8 Encoding TNAP-DJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders.Current osteoporosis reports · 2020Review
- rAAVrh74.MCK.Molecular therapy. Methods & clinical development · 2019Article
- Alkaline Phosphatase Replacement Therapy for Hypophosphatasia in Development and Practice.Advances in experimental medicine and biology · 2019Review
- Alkaline Phosphatase Replacement Therapy.Advances in experimental medicine and biology · 2019Review
- Tailoring the AAV2 capsid vector for bone-targeting.Pediatric research · 2018Article
- Bone-Targeted Alkaline Phosphatase Treatment of Mandibular Bone and Teeth in Lethal Hypophosphatasia via an scAAV8 Vector.Molecular therapy. Methods & clinical development · 2018Article
- Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy.Drug design, development and therapy · 2018Review
- Alkaline Phosphatase Controls Lineage Switching of Mesenchymal Stem Cells by Regulating the LRP6/GSK3β Complex in Hypophosphatasia.Theranostics · 2018Article
- Alkaline Phosphatase and Hypophosphatasia.Calcified tissue international · 2016Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypophosphatasia (HPP) is an inherited disease caused by a deficiency of tissue-nonspecific alkaline phosphatase (TNALP). The major symptom of human HPP is hypomineralization, rickets, or osteomalacia, although the clinical severity is highly variable. The phenotypes of TNALP knockout (Akp2(-/-)) mice mimic those of the severe infantile form of HPP. Akp2(-/-) mice appear normal at birth, but they develop growth failure, epileptic seizures, and hypomineralization and die by 20 days of age. Previously, we have shown that the phenotype of Akp2(-/-) mice can be prevented by enzyme replacement of bone-targeted TNALP in which deca-aspartates are linked to the C-terminus of soluble TNALP (TNALP-D10). In the present study, we evaluated the therapeutic effects of adeno-associated virus serotype 8 (AAV8) vectors that express various forms of TNALP, including TNALP-D10, soluble TNALP tagged with the Flag epitopes (TNALP-F), and native glycosylphosphatidylinositol-anchored TNALP (TNALP-N). A single intravenous injection of 5×10(10) vector genomes of AAV8-TNALP-D10 into Akp2(-/-) mice at day 1 resulted in prolonged survival and phenotypic correction. When AAV8-TNALP-F was injected into neonatal Akp2(-/-) mice, they also survived without epileptic seizures. Interestingly, survival effects were observed in some animals treated with AAV8-TNALP-N. All surviving Akp2(-/-) mice showed a healthy appearance and a normal activity with mature bone mineralization on X-rays. These results suggest that sustained alkaline phosphatase activity in plasma is essential and sufficient for the rescue of Akp2(-/-) mice. AAV8-mediated systemic gene therapy appears to be an effective treatment for the infantile form of human HPP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.