149
Views
17
CrossRef citations to date
0
Altmetric
Patent Evaluations

Therapeutic potential of klotho–FGF23 fusion polypeptides: WO2009095372

, MD PhD
Pages 981-985 | Published online: 12 May 2010
 

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 1α(OH)ase to reduce 1,25(OH)2D 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.

Acknowledgements

The author wishes to thank Drs. Teruyo Nakatani and Mutsuko Ohnishi of Harvard School of Dental Medicine, Boston for performing mouse genetics studies which are partly supported by a grant (R01-DK077276) from NIDDK and institutional supports from the Harvard School of Dental Medicine in Boston, USA.

Notes

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.