118
A Novel FGFR4 Antibody to Treat Cardiac Death in Chronic Kidney Disease (CKD)
Lead Discovery Center
Antibody
Genitourinary disease
Hit To Lead or Lead Optimization
• 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.
WO2012177481A2
Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metabolism, (2015)
