Methods for the treatment of X-linked hypophosphatemia and related disorders
The disclosure provides methods of treating X-linked hypophosphatemia, related bone demineralization and renal phosphate wasting disorders in a mammalian subject. The methods comprise administering to the subject an effective amount of a polyarginine peptide.
1. A method for treating X-linked hypophosphatemia in a mammalian subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polyarginine peptide comprising at least four consecutive arginine residues.
2. The method of claim 1 , wherein the subject is suffering from X-linked hypophosphatemic rickets.
3. The method of claim 1 , wherein the subject is suffering from X-linked hypophosphatemic osteomalacia.
4. The method of claim 1 , wherein the polyarginine peptide comprises from 5 to 16 consecutive arginine residues.
5. The method of claim 1 , wherein the polyarginine peptide is selected from the group consisting of penta-D-arginine, hexa-D-arginine, hepta-D-arginine, octa-D-arginine, or nona-D-arginine, or a combination thereof.
6. The method of claim 1 , wherein the polyarginine peptide is hexa-D-arginine.
7. The method of claim 1 , wherein the polyarginine peptide is fused to a targeting agent.
8. The method of claim 7 , wherein the targeting agent is a bone targeting agent.
9. The method of claim 8 , wherein the bone targeting agent is selected from the group consisting of bisphosphonate, a hydroxybisphosphonate, a phosphonate, a phosphate, an aminomethylenephosphonic acid, and an acidic peptide.
10. A method for treating hypophosphatemic osteomalacia in a mammalian subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polyarginine peptide comprising at least four consecutive arginine residues.
11. The method of claim 10 , wherein the hypophosphatemic osteomalacia is tumor-induced osteomalacia or is due to X-linked hypophosphatemia.
12. The method of claim 10 , wherein the polyarginine peptide comprises from 5 to 16 consecutive arginine residues.
13. The method of claim 10 , wherein the polyarginine peptide is selected from the group consisting of penta-D-arginine, hexa-D-arginine, hepta-D-arginine, octa-D-arginine, or nona-D-arginine, or a combination thereof.
14. The method of claim 10 , wherein the polyarginine peptide comprises hexa-D-arginine.
15. The method of claim 10 , wherein the polyarginine peptide is fused to a targeting agent.
16. The method of claim 15 , wherein the targeting agent is a bone targeting agent.
17. The method of claim 16 , wherein the bone targeting agent is selected from the group consisting of bisphosphonate, a hydroxybisphosphonate, a phosphonate, a phosphate, an aminomethylenephosphonic acid, and an acidic peptide.
18. A method for enhancing or normalizing bone growth or bone mineralization in a subject suffering from hypophosphatemic rickets or hypophosphatemic osteomalacia, comprising administering to the subject a therapeutically effective amount of a polyarginine peptide comprising at least four consecutive arginine residues.
19. The method of claim 18 , wherein the polyarginine peptide comprises hexa-D-arginine.
20. The method of claim 19 , wherein the polyarginine peptide is fused to a bone targeting agent.