A novel therapeutic strategy for skeletal disorders: Proof of concept of gene therapy for X-linked hypophosphatemia - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Science Advances Year : 2021

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

Natalie Danièle
Fabienne Rajas

Abstract

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.
Fichier principal
Vignette du fichier
sciadv.abj5018.pdf (1.73 Mo) Télécharger le fichier
Origin Publication funded by an institution

Dates and versions

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

Identifiers

Cite

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⟩
30 View
68 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More