Therapeutic Potential of Klotho-FGF23 Fusion Polypeptides: WO2009095372

Overview

Journal Expert Opin Ther Pat

Publisher Informa Healthcare

Date 2010 May 13

PMID 20459364

Citations 10

Authors

Mohammed S Razzaque

Affiliations

Soon will be listed here.

Abstract

The molecular interaction of fibroblast growth factor 23 (FGF23) and klotho is essential for physiologic regulation of phosphate balance. In the absence of klotho, the FGF23 protein cannot exert its physiologic functions, as demonstrated by in vivo mouse genetic studies. Bioactive FGF23 protein loses its phosphate lowering effects in genetically modified mice with no klotho activity. The FGF23-klotho system not only affects phosphate homeostasis but can also influence parathyroid hormone (PTH) and vitamin D activities. Dysregulation of the FGF23-klotho system is noted in a number of human acquired and genetic diseases, including chronic kidney disease. Vitamin D is a strong inducer of both FGF23 and klotho expression, while FGF23 can suppress the renal expression of 1alpha(OH)ase to reduce 1,25(OH)(2)D activity. An understanding of the complex interactions of phosphate, vitamin D and PTH with the FGF23-klotho system has paved the way to explore the therapeutic benefits of modulating the FGF23-klotho system in diseases associated with abnormal mineral ion balance. The patent (WO2009095372) under discussion proposes using fusion polypeptides to manipulate the FGF23-klotho system.

Citing Articles

Klotho: a novel biomarker for cancer.

Zhou X, Wang X J Cancer Res Clin Oncol. 2014; 141(6):961-9.

PMID: 25086986 DOI: 10.1007/s00432-014-1788-y.

FGF23-induced hypophosphatemia persists in Hyp mice deficient in the WNT coreceptor Lrp6.

Uchihashi K, Nakatani T, Goetz R, Mohammadi M, He X, Razzaque M Contrib Nephrol. 2013; 180:124-37.

PMID: 23652555 PMC: 3723105. DOI: 10.1159/000346792.

Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism.

Hu M, Shiizaki K, Kuro-O M, Moe O Annu Rev Physiol. 2013; 75:503-33.

PMID: 23398153 PMC: 3770142. DOI: 10.1146/annurev-physiol-030212-183727.

Fibroblast growth factor 23: friend or foe in uremia?.

Moe O J Clin Invest. 2012; 122(7):2354-6.

PMID: 22728930 PMC: 3386835. DOI: 10.1172/JCI64184.

The role of Klotho in energy metabolism.

Razzaque M Nat Rev Endocrinol. 2012; 8(10):579-87.

PMID: 22641000 PMC: 3704949. DOI: 10.1038/nrendo.2012.75.

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