ArticleMolecular therapy. Methods & clinical development2016
Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
The trial behind it
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Who cites it
17 citing papers in PubMed, 25 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
- Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.Journal of the American Dental Association (1939) · 2024Review
- Gene Therapy Using Recombinant AAV Type 8 Vector Encoding TNAP-DJBMR plus · 2023Article
- Prenatal enzyme replacement therapy forRegenerative therapy · 2021Article
- 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
- AnStem cells international · 2021Review
- Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders.Current osteoporosis reports · 2020Review
- rAAVrh74.MCK.Molecular therapy. Methods & clinical development · 2019Article
- Comparison of Gene Delivery to the Kidney by Adenovirus, Adeno-Associated Virus, and Lentiviral Vectors After Intravenous and Direct Kidney Injections.Human gene therapy · 2019Article
- Alkaline Phosphatase Replacement Therapy for Hypophosphatasia in Development and Practice.Advances in experimental medicine and biology · 2019Review
- Bone-Targeted Alkaline Phosphatase Treatment of Mandibular Bone and Teeth in Lethal Hypophosphatasia via an scAAV8 Vector.Molecular therapy. Methods & clinical development · 2018Article
- Hypophosphatasia: From Diagnosis to Treatment.Current rheumatology reports · 2018Review
- Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy.Drug design, development and therapy · 2018Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypophosphatasia (HPP) is an inherited disease caused by genetic mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). This results in defects in bone and tooth mineralization. We recently demonstrated that TNALP-deficient (Akp2 (-/-) ) mice, which mimic the phenotype of the severe infantile form of HPP, can be treated by intravenous injection of a recombinant adeno-associated virus (rAAV) expressing bone-targeted TNALP with deca-aspartates at the C-terminus (TNALP-D10) driven by the tissue-nonspecific CAG promoter. To develop a safer and more clinically applicable transduction strategy for HPP gene therapy, we constructed a self-complementary type 8 AAV (scAAV8) vector that expresses TNALP-D10 via the muscle creatine kinase (MCK) promoter (scAAV8-MCK-TNALP-D10) and examined the efficacy of muscle-directed gene therapy. When scAAV8-MCK-TNALP-D10 was injected into the bilateral quadriceps of neonatal Akp2 (-/-) mice, the treated mice grew well and survived for more than 3 months, with a healthy appearance and normal locomotion. Improved bone architecture, but limited elongation of the long bone, was demonstrated on X-ray images. Micro-CT analysis showed hypomineralization and abnormal architecture of the trabecular bone in the epiphysis. These results suggest that rAAV-mediated, muscle-specific expression of TNALP-D10 represents a safe and practical option to treat the severe infantile form of 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.