Activin-actrii antagonists and uses for treating bone and other disorders

Abstract

Provided herein are methods for the treatment of bone disorders that are associated with kidney disease wherein the methods comprise administration of Activin-ActRIIA inhibitors to a subject in need of the treatment. Also provided herein are methods and compositions for the treatment of low turnover bone disorders wherein the methods comprise administration of Activin-ActRIIA inhibitors to a subject in need of the treatment. Further provided herein are compositions for the treatment of bone disorders that are associated with kidney disease and compositions for the treatment of low turnover bone disorders and vascular calcification.

What is claimed: 
     
         1 . A method for treating an adynamic bone disorder in a subject, wherein the method comprises administering a therapeutically effective amount of an ActRII inhibitor to a subject in need of treatment of the adynamic bone disorder. 
     
     
         2 . A method for treating an adynamic bone disorder form of CKD-MBD in a subject, wherein the method comprises administering a therapeutically effective amount of an ActRII inhibitor to a subject in need of treatment of the adynamic bone disorder form of CKD-MBD. 
     
     
         3 . The method of  claim 1  or  2 , wherein the adynamic bone disorder is characterized by absence of tetracycline incorporation into mineralized bone. 
     
     
         4 . A method for treating a low bone turnover form of CKD-MBD in a subject, wherein the method comprises administering a therapeutically effective amount of an ActRII inhibitor to a subject in need of treatment of the low bone turnover form of CKD-MBD. 
     
     
         5 . The method of  claim 4 , wherein the low bone turnover form of CKD-MBD is osteomalacia. 
     
     
         6 . A method for treating a bone disorder characterized by hyperphosphatemia in a subject, wherein the method comprises administering a therapeutically effective amount of an ActRII inhibitor to a subject in need of treatment of the bone disorder characterized by hyperphosphatemia. 
     
     
         7 . A method for treating vascular calcification in a subject, wherein the method comprises administering a therapeutically effective amount of an ActRII inhibitor to a subject in need of treatment of atherosclerotic calcification. 
     
     
         8 . A method for treating a renal disease in a subject, wherein the method comprises administering a therapeutically effective amount of an ActRII inhibitor to a subject in need of treatment of the renal disease. 
     
     
         9 . The method of  claim 8 , wherein the renal disease is renal fibrosis. 
     
     
         10 . A method for reducing vascular calcium levels in a subject diagnosed with vascular calcification, wherein the method comprises administering a therapeutically effective amount of an ActRII inhibitor to the subject. 
     
     
         11 . The method of  claim 1 ,  2 ,  4 ,  6 ,  7 ,  8 , or  10  wherein the ActRII inhibitor is a polypeptide comprising an amino acid sequence selected from the group consisting of:
 a. 90% identical to SEQ ID NO:2; 
 b. 95% identical to SEQ ID NO:2; 
 c. 98% identical to SEQ ID NO:2; 
 d. SEQ ID NO:2; 
 e. 90% identical to SEQ ID NO:3; 
 f. 95% identical to SEQ ID NO:3; 
 g. 98% identical to SEQ ID NO:3; 
 h. SEQ ID NO:3; 
 i. 90% identical to SEQ ID NO:6; 
 j. 95% identical to SEQ ID NO:6; 
 k. 98% identical to SEQ ID NO:6; 
 l. SEQ ID NO:6; 
 m. 90% identical to SEQ ID NO:7; 
 n. 95% identical to SEQ ID NO:7; 
 o. 98% identical to SEQ ID NO:7; 
 p. SEQ ID NO:7; 
 q. 90% identical to SEQ ID NO: 12; 
 r. 95% identical to SEQ ID NO: 12; 
 s. 98% identical to SEQ ID NO: 12; 
 t. SEQ ID NO:12; 
 u. 90% identical to SEQ ID NO: 17; 
 v. 95% identical to SEQ ID NO: 17; 
 w. 98% identical to SEQ ID NO: 17; 
 x. SEQ ID NO: 17; 
 y. 90% identical to SEQ ID NO:20; 
 z. 95% identical to SEQ ID NO:20; 
 aa. 98% identical to SEQ ID NO:20; 
 bb. SEQ ID NO:20; 
 cc. 90% identical to SEQ ID NO:21; 
 dd. 95% identical to SEQ ID NO:21; 
 ee. 98% identical to SEQ ID NO:21; 
 ff. SEQ ID NO:21 
 gg. 90% identical to SEQ ID NO:23; 
 hh. 95% identical to SEQ ID NO:23; 
 ii. 98% identical to SEQ ID NO:23; 
 jj. SEQ ID NO:23 
 kk. 90% identical to SEQ ID NO:25; 
 ll. 95% identical to SEQ ID NO:25; 
 mm. 98% identical to SEQ ID NO:25; and 
 nn. SEQ ID NO:25. 
 
     
     
         12 . The method of  claim 1 ,  2 ,  4 ,  6 ,  7 ,  8 , or  10 , wherein the ActRII inhibitor is a polypeptide comprising the amino acid sequence of SEQ ID NO:7. 
     
     
         13 . The method of  claim 1 ,  2 ,  4 ,  6 ,  7 ,  8 , or  10 , wherein the ActRII inhibitor is administered parentally. 
     
     
         14 . The method of  claim 1 ,  2 ,  4 ,  6 ,  7 ,  8 , or  10 , wherein the subject is less than 18 years old. 
     
     
         15 . The method of  claim 1 ,  2 ,  4 ,  6 ,  7 ,  8 , or  10 , wherein the method increases the height of the subject. 
     
     
         16 . The method of  claim 1 ,  2 ,  4 ,  6 ,  7 ,  8 , or  10 , wherein the subject has end stage renal disease. 
     
     
         17 . The method of  claim 1 ,  2 ,  4 ,  6 ,  7 ,  8 , or  10 , wherein the subject undergoes dialysis.