Asset

  • No.

    118

  • Asset Title

    A Novel FGFR4 Antibody to Treat Cardiac Death in Chronic Kidney Disease (CKD)

  • Organization

    Lead Discovery Center

  • Product Type

    Antibody

  • Therapeutic Area

    Genitourinary disease

  • Development Stage

    Hit To Lead or Lead Optimization

  • Technical Summary

    • FGFR4-Ab prevents (i) FGF23/FGFR4 interaction, and (ii) LVH. 

    • Chronic kidney disease (CKD) is a worldwide public health threat that increases risk of death due to cardiovascular complications, including left ventricular hypertrophy (LVH). 

    • Novel therapeutic targets are needed to design treatments to alleviate the cardiovascular burden of CKD. 

    • FGF23 exclusively activates FGFR4 on cardiac myocytes to stimulate phospholipase Cg/calcineurin/nuclear factor of activated T cell signaling.

    • A specific FGFR4-blocking antibody inhibits FGF23-induced hypertrophy of isolated cardiac myocytes and attenuates LVH in rats with CKD. 

    • Mice lacking FGFR4 do not develop LVH in response to elevated FGF23, whereas knockin mice carrying an FGFR4 gain-of-function mutation spontaneously develop LVH. 

    • FGF23 promotes LVH by activating FGFR4, thereby establishing FGFR4 as a pharmacological target for reducing cardiovascular risk in CKD. 

  • Patent

    WO2012177481A2

  • Publication

    Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metabolism, (2015)

  • Attachment

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