In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia

Achondroplasia is a rare genetic disorder caused by mutations in the Fibroblast Growth Factor receptor 3 (FGFR3). These mutations lead to aberrant increase of inhibitory signaling in proliferating chondrocytes at the growth plate. Recifercept is a potential treatment for this disease using a decoy a...

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Bibliographic Details
Published in:PloS one 2020-12, Vol.15 (12), p.e0244368-e0244368
Main Authors: Gonçalves, Diogo, Rignol, Guylène, Dellugat, Pierre, Hartmann, Guido, Sarrazy Garcia, Stephanie, Stavenhagen, Jeffrey, Santarelli, Luca, Gouze, Elvire, Czech, Christian
Format: Article
Language:English
Subjects:
Achondroplasia
Achondroplasia - drug therapy
Achondroplasia - genetics
Achondroplasia - metabolism
Animals
Biology and Life Sciences
Body Weight - drug effects
Bone Development - drug effects
Care and treatment
Cell Differentiation - drug effects
Cell Line
Cell Proliferation - drug effects
Disease Models, Animal
Engineering and Technology
Female
Fibroblast growth factor receptors
Fibroblast Growth Factors - metabolism
Health aspects
Humans
Male
Medicine and Health Sciences
Mice
Mice, Transgenic
Mutation
Protein Binding - drug effects
Receptor, Fibroblast Growth Factor, Type 3 - administration & dosage
Receptor, Fibroblast Growth Factor, Type 3 - genetics
Receptor, Fibroblast Growth Factor, Type 3 - metabolism
Receptor, Fibroblast Growth Factor, Type 3 - pharmacology
Research and Analysis Methods
Signal Transduction - drug effects
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Summary:Achondroplasia is a rare genetic disorder caused by mutations in the Fibroblast Growth Factor receptor 3 (FGFR3). These mutations lead to aberrant increase of inhibitory signaling in proliferating chondrocytes at the growth plate. Recifercept is a potential treatment for this disease using a decoy approach to sequester FGFR3 ligands subsequently normalizing activation of the mutated FGFR3 receptor. Recifercept binds to FGF isoforms in vitro and in cellular model systems and reduces FGFR3 signaling. In addition, in a transgenic mouse model of achondroplasia, Recifercept restores reduced body weight and long bone growth in these mice. These data suggest that Recifercept treatment could lead to clinical benefits in children treated with this molecule.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0244368