Prenatal enzyme replacement therapy for Akp2−/− mice with lethal hypophosphatasia
| العنوان: | Prenatal enzyme replacement therapy for Akp2−/− mice with lethal hypophosphatasia |
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| المؤلفون: | Masataka Kasahara, Haruhiko Sago, Aki Nakamura-Takahashi, Nana Saso, Aikou Okamoto, Osamu Samura, José Luis Millán, Sonoko Narisawa, Akihiro Hasegawa, Akihiro Umezawa |
| المصدر: | Regenerative Therapy, Vol 18, Iss, Pp 168-175 (2021) Regenerative Therapy |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Medicine (General), HPP, hypophosphatasia, TNAP, tissue-nonspecific alkaline phosphatase, Biomedical Engineering, Bone calcification, Prenatal diagnosis, Hypophosphatasia, Calcification, Biomaterials, R5-920, Internal medicine, Alkaline phosphatase, medicine, Survival rate, ALP, alkaline phosphatase, QH573-671, business.industry, nutritional and metabolic diseases, Enzyme replacement therapy, medicine.disease, ERT, enzyme replacement therapy, Prenatal treatment, Fetal therapy, Endocrinology, Original Article, PPi, inorganic pyrophosphate, PLP, pyridoxal 5′-phosphate, business, Cytology, Developmental Biology |
| الوصف: | Hypophosphatasia (HPP) is a congenital skeletal disease. Impairment of bone mineralization and seizures are due to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP). Enzyme replacement therapy (ERT) is available as a highly successful treatment for pediatric-onset HPP. However, the potential for prenatal ERT has not been fully investigated to date. In this study, we assessed outcomes and maternal safety using a combinational approach with prenatal and postnatal administration of recombinant TNAP in Akp2−/− mice as a model of infantile HPP. For the prenatal ERT, we administered subcutaneous injections of recombinant TNAP to pregnant mice from embryonic day 11.5–14.5 until delivery, and then sequentially to Akp2−/− pups from birth to day 18. For the postnatal ERT, we injected Akp2−/− pups from birth until day 18. Prenatal ERT did not cause any ectopic mineralization in heterozygous maternal mice. Both prenatal and postnatal ERT preserved growth, survival rate and improved bone calcification in Akp2−/− mice. However, the effects of additional prenatal treatment to newborn mice appeared to be minimal, and the difference between prenatal and postnatal ERT was subtle. Further improvement of the prenatal ERT schedule and long-term observation will be required. The present paper sets a standard for such future studies. |
| اللغة: | English |
| تدمد: | 2352-3204 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fcdb28092ad1d917c704a2ae0de2d9c1 http://www.sciencedirect.com/science/article/pii/S235232042100047X |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fcdb28092ad1d917c704a2ae0de2d9c1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523204 |
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