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Article Dans Une Revue Science Advances Année : 2021

A novel therapeutic strategy for skeletal disorders: Proof of concept of gene therapy for X-linked hypophosphatemia

Natalie Danièle
Fabienne Rajas

Résumé

Adeno-associated virus (AAV) vectors are a well-established gene transfer approach for rare genetic diseases. Nonetheless, some tissues, such as bone, remain refractory to AAV. X-linked hypophosphatemia (XLH) is a rare skeletal disorder associated with increased levels of fibroblast growth factor 23 (FGF23), resulting in skeletal deformities and short stature. The conventional treatment for XLH, lifelong phosphate and active vitamin D analogs supplementation, partially improves quality of life and is associated with severe long-term side effects. Recently, a monoclonal antibody against FGF23 has been approved for XLH but remains a high-cost lifelong therapy. We developed a liver-targeting AAV vector to inhibit FGF23 signaling. We showed that hepatic expression of the C-terminal tail of FGF23 corrected skeletal manifestations and osteomalacia in a XLH mouse model. Our data provide proof of concept for AAV gene transfer to treat XLH, a prototypical bone disease, further expanding the use of this modality to treat skeletal disorders.
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Dates et versions

inserm-03687057 , version 1 (03-06-2022)

Identifiants

Citer

Volha Zhukouskaya, Louisa Jauze, Séverine Charles, Christian Leborgne, Stéphane Hilliquin, et al.. A novel therapeutic strategy for skeletal disorders: Proof of concept of gene therapy for X-linked hypophosphatemia. Science Advances , 2021, 7 (44), pp.eabj5018. ⟨10.1126/sciadv.abj5018⟩. ⟨inserm-03687057⟩
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