COMPOSITIONS AND METHODS TO REGULATE SERUM PHOSPHATE

摘要

The present invention relates to methods and compositions for regulating serum phosphate or phosphate homeostasis. More specifically, the present invention relates to methods and compositions for increasing or decreasing serum phosphate levels for the treatment and/or prevention of a variety of phosphate-related diseases by modulating the activity or expression of FRP 4, FGF 23 and PHEX. The methods of the invention are useful for increasing phosphate re-absorption or serum phosphate by delivering to a subject an agent that inhibits the activity of FGF 23 or FRP-4 or for decreasing phosphate re-absorption or serum phosphate by delivering to a subject an agent that enhances the activity FGF 23 or FRP-4 or inhibits the activity of PHEX. Also provided are methods for modulating renal phosphate transport, alleviating oncogenic osteomalacia-associated symptoms, treating phosphate homeostasis-related disease and modulating the phenotype of a neoplastic cell associated with OOM cell or a cell associated with phosphate homeostasis. In addition, the invention provides methods for detecting and monitoring expression of one or more of the FRP 4, FGF 23 and PHEX gene(s) or proteins. Finally, the invention provides methods for screening candidate agents to identify compositions that modify the activity or expression of FRP 4, FGF 23 and PHEX.