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PLoS One ; 15(12): e0244368, 2020.
Article in English | MEDLINE | ID: mdl-33370388

ABSTRACT

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.


Subject(s)
Achondroplasia/drug therapy , Fibroblast Growth Factors/metabolism , Mutation , Receptor, Fibroblast Growth Factor, Type 3/administration & dosage , Achondroplasia/genetics , Achondroplasia/metabolism , Animals , Body Weight/drug effects , Bone Development/drug effects , Cell Differentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Transgenic , Protein Binding/drug effects , Receptor, Fibroblast Growth Factor, Type 3/genetics , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Receptor, Fibroblast Growth Factor, Type 3/pharmacology , Signal Transduction/drug effects
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