Methods for the treatment of x-linked hypophosphatemia and related disorders

Abstract

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 .- 20 . (canceled) 
     
     
         21 . A pharmaceutical composition comprising a polyarginine peptide comprising at least four consecutive arginine residues, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of saline, solvents, a dispersion media, a coating, an antibacterial agent, an antifungal agent, an isotonic agent, and an absorption delaying agent. 
     
     
         23 . The pharmaceutical composition of  claim 21 , wherein the pharmaceutically acceptable carrier comprises a biodegradable, biocompatible polymer matrix. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the polymer matrix is selected from the group consisting of gelatin, collagen, fibronectin, elastin, cellulose acetate, cellulose nitrate, polysaccharide, fibrin, and combinations thereof. 
     
     
         25 . The pharmaceutical composition of  claim 23 , wherein the polyarginine peptide is embedded in the polymer matrix. 
     
     
         26 . The pharmaceutical composition of  claim 21 , wherein the composition is formulated for subcutaneous, intravenous, intradermal, intraperitoneal, oral, topical, transdermal, inhalational, intraocular, iontophoretic, or transmucosal administration. 
     
     
         27 . The pharmaceutical composition of  claim 21 , wherein the composition is formulated for controlled release of the polyarginine peptide. 
     
     
         28 . The pharmaceutical composition of  claim 21 , wherein the polyarginine peptide comprises from 5 to 16 consecutive arginine residues. 
     
     
         29 . The pharmaceutical composition of  claim 21 , wherein the polyarginine peptide is selected from the group consisting of penta-L-arginine (SEQ ID NO: 1), hexa-L-arginine (SEQ ID NO: 2), hepta-L-arginine (SEQ ID NO: 3), octa-L-arginine (SEQ ID NO: 4), nona-L-arginine (SEQ ID NO: 5), penta-D-arginine, hexa-D-arginine, hepta-D-arginine, octa-D-arginine, nona-D-arginine, and combinations thereof. 
     
     
         30 . The pharmaceutical composition of  claim 21 , wherein the polyarginine peptide is hexa-D-arginine. 
     
     
         31 . The pharmaceutical composition of  claim 21 , wherein the polyarginine peptide is fused to a targeting agent. 
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein the targeting agent is a bone targeting agent. 
     
     
         33 . The pharmaceutical composition of  claim 32 , wherein the bone targeting agent is selected from the group consisting of a bisphosphonate, a hydroxybisphosphonate, a phosphonate, a phosphate, an aminomethylenephosphonic acid, and an acidic peptide. 
     
     
         34 . The pharmaceutical composition of  claim 32 , wherein the bone targeting agent is covalently linked to the polyarginine peptide via a linker that is cleaved under physiological conditions. 
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein the linker is (i) an acid-cleavable linker, (ii) selected from a group consisting of an enol ether, ketal, imine, oxime, hydrazone, semicarbazone, acylimide, and methylene radical, (iii) is a hydrolytically cleavable linker, or (iv) is cleaved enzymatically.