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

(1, 2, 3, 4, 5) , (1, 2, 6) , (1, 2) , (1, 2) , (3, 7) , (3) , (3) , (3) , (1) , (1) , (6) , (4, 5) , (1, 2) , (3, 5, 8) , (3) , (1, 2)
1
2
3
4
5
6
7
8
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⟩
8 View
6 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More