Inhibiting binding of FGF23 to the binary FGFR-Klotho complex for the treatment of chronic kidney disease and symptoms and/or complications thereof
The present invention is directed to a method of treating chronic kidney disease. This method involves selecting a subject with chronic kidney disease and administering to the selected subject an inhibitor of FGF23-Klotho-FGF receptor complex formation under conditions effective to treat the chronic kidney disease. The present invention is also directed to a method of treating or preventing chronic kidney disease symptoms and/or complications, which involves selecting a subject with a chronic kidney disease symptom and/or complication and and administering to the selected subject an inhibitor of FGF23-Klotho-FGF receptor complex formation under conditions effective to treat the chronic kidney disease.
1. A method of inhibiting FGF23 signalling in a subject having chronic kidney disease, said method comprising:
selecting a subject with chronic kidney disease; and
administering to the selected subject an inhibitor of FGF23 signaling under conditions effective to inhibit FGF23 signaling in the selected subject, wherein the inhibitor comprises a C-terminal fragment of FGF23 consisting of the amino acid sequence of SEQ ID NO:12 or amino acid residues 1 to 21 of SEQ ID NO:11.
2. The method according to claim 1 , wherein the selected subject hyperparathyroidism.
3. The method according to claim 1 , wherein the selected subject has vascular calcification.
4. The method according to claim 1 , wherein the selected subject has cardiovascular disease.
5. The method according to claim 1 , wherein the selected subject has suppressed 1,25-vitamin D production.
6. The method according to claim 1 , wherein the FGF23 has the amino acid sequence of SEQ ID NO:3.
7. The method according to claim 1 , wherein said administering is carried out orally, parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, by intranasal instillation, by implantation, by intracavitary or intravesical instillation, intraocularly, intraarterially, intralesionally, transdermally, or by application to mucous membranes.
8. The method according to claim 1 , wherein the inhibitor is administered with a pharmaceutically-acceptable carrier.
9. The method according to claim 1 , wherein the inhibitor is administered together with vitamin D or a vitamin D receptor agonist.
10. The method according to claim 1 , wherein the subject is a mammal.
11. The method according to claim 1 , wherein the subject is a human.
12. The method according to claim 1 , wherein the inhibitor binds a Klotho-FGF receptor binary complex.
13. The method according to claim 1 , wherein the inhibitor consists of the amino acid sequence of SEQ ID NO:12.
14. The method according to claim 1 , wherein the inhibitor consists of the amino acid sequence of SEQ ID NO:11.