Research and Development, Rare Disease Unit, Pfizer, Nice, France.
TOLREMO Therapeutics AG, Muttenz, Switzerland.
PLoS One. 2020 Dec 28;15(12):e0244368. doi: 10.1371/journal.pone.0244368. eCollection 2020.
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.
软骨发育不全症是一种罕见的遗传性疾病,由成纤维细胞生长因子受体 3(FGFR3)中的突变引起。这些突变导致生长板中增殖的软骨细胞中抑制信号异常增加。Recifercept 是一种潜在的治疗方法,采用诱饵方法来隔离 FGFR3 配体,从而使突变的 FGFR3 受体的激活正常化。Recifercept 在体外和细胞模型系统中与 FGF 同工型结合,并降低 FGFR3 信号。此外,在软骨发育不全症的转基因小鼠模型中,Recifercept 恢复了这些小鼠的体重减轻和长骨生长。这些数据表明,Recifercept 治疗可能会给接受该分子治疗的儿童带来临床益处。