ArticleHuman gene therapy2012
Successful gene therapy in utero for lethal murine hypophosphatasia.
Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 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
- Prenatal Delivery of Enzyme Replacement Therapy to Fetuses Affected by Early-Onset Lysosomal Storage Diseases.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Hypophosphatasia: A case report.World journal of clinical cases · 2025Article
- 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
- Fetal gene therapy.Journal of inherited metabolic disease · 2024Review
- Gene modification therapies for hereditary diseases in the fetus.Prenatal diagnosis · 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
- Prenatal enzyme replacement therapy forRegenerative therapy · 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
- A constitutive knockout of murine carbamoyl phosphate synthetase 1 results in death with marked hyperglutaminemia and hyperammonemia.Journal of inherited metabolic disease · 2019Article
- Therapeutic expression of human clotting factors IX and X following adeno-associated viral vector-mediated intrauterine gene transfer in early-gestation fetal macaques.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 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
- Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy.Drug design, development and therapy · 2018Review
- Skeletal Dysplasias: Growing Therapy for Growing Bones.Frontiers in pharmacology · 2017Review
- Alkaline Phosphatase and Hypophosphatasia.Calcified tissue international · 2016Review
- Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector.Molecular therapy. Methods & clinical development · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypophosphatasia (HPP), caused by mutations in the gene ALPL encoding tissue-nonspecific alkaline phosphatase (TNALP), is an inherited systemic skeletal disease characterized by mineralization defects of bones and teeth. The clinical severity of HPP varies widely, from a lethal perinatal form to mild odontohypophosphatasia showing only dental manifestations. HPP model mice (Akp2(-/-)) phenotypically mimic the severe infantile form of human HPP; they appear normal at birth but die by 2 weeks of age because of growth failure, hypomineralization, and epileptic seizures. In the present study, we investigated the feasibility of fetal gene therapy using the lethal HPP model mice. On day 15 of gestation, the fetuses of HPP model mice underwent transuterine intraperitoneal injection of adeno-associated virus serotype 9 (AAV9) expressing bone-targeted TNALP. Treated and delivered mice showed normal weight gain and seizure-free survival for at least 8 weeks. Vector sequence was detected in systemic organs including bone at 14 days of age. ALP activities in plasma and bone were consistently high. Enhanced mineralization was demonstrated on X-ray images of the chest and forepaw. Our data clearly demonstrate that systemic injection of AAV9 in utero is an effective strategy for the treatment of lethal HPP mice. Fetal gene therapy may be an important choice after prenatal diagnosis of life-threatening 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.