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

被引：19

作者：

Goncalves, Diogo ^{[1
]}

Rignol, Guylene ^{[1
]}

Dellugat, Pierre ^{[1
]}

Hartmann, Guido ^{[1
,2
]}

Sarrazy Garcia, Stephanie ^{[3
]}

Stavenhagen, Jeffrey ^{[4
]}

Santarelli, Luca ^{[5
]}

Gouze, Elvire ^{[6
]}

Czech, Christian ^{[1
]}

机构：

[1] Pfizer, Rare Dis Unit, Res & Dev, Nice, France

[2] TOLREMO Therapeut AG, Muttenz, Switzerland

[3] Bionea, Biot, France

[4] Therini Bio, San Francisco, CA USA

[5] VectivBio, Basel, Switzerland

[6] Univ Cote Azur, CNRS, INSERM, iBV, Nice, France

来源：

PLOS ONE | 2020年 / 15卷 / 12期

关键词：

FGFR3; DIFFERENTIATION; MUTATIONS; CARTILAGE; DWARFISM; G380R;

D O I：

10.1371/journal.pone.0244368

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 27 条

[1]

Beenken A, 2012, ADV EXP MED BIOL, V728, P1, DOI 10.1007/978-1-4614-0887-1_1

[2]

BELLUS GA, 1995, AM J HUM GENET, V56, P368

[3] TransCon CNP, a Sustained-Release C-Type Natriuretic Peptide Prodrug, a Potentially Safe and Efficacious New Therapeutic Modality for the Treatment of Comorbidities Associated with Fibroblast Growth Factor Receptor 3-Related Skeletal Dysplasias [J].