Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) have been proposed as potential drug targets for the treatment of obesity. The aim of this study was to assess the potential toxicity in rats of three anti-FGFR1c mAbs with differential binding activity prior to clinical development. Groups of male rats received weekly injections of either one of two FGFR1c-specific mAbs or an FGFR1c/FGFR4-specific mAb at 10 mg/kg for up to 4 weeks. All three mAbs caused significant reductions in food intake and weight loss leading to some animals being euthanized early for welfare reasons. In all three groups given these mAbs, microscopic changes were seen in the bones and heart valves. In the bones of the femoro-tibial joint, thickening of the diaphyseal cortex of long bones, due to deposition of well organized new lamellar bone, indicated that an osteogenic effect was observed. In the heart, valvulopathy described as an endocardial myxomatous change affecting the mitral, pulmonary, tricuspid and aortic valves was observed in all mAb-treated animals. The presence of FGFR1 mRNA expression in the heart valves was confirmed using in situ hybridization. Targeting the FGF-FGFR1c pathway with anti-FGFR1c mAbs leads to drug induced valvulopathy in rats. In effect, this precluded the development of these mAbs as potential anti-obesity drugs. The valvulopathy observed was similar to that described for fenfluramine and dexafenfluramine. The pathogenesis of the drug-induced valvulopathy is considered FGFR1c-mediated, based on the specificity of the mAbs and FGFR1 mRNA expression in the heart valves.Keywords: Fibroblast Growth Factors; Heart; Rat; Valves; Valvulopathy.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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