Treatment of Fibrodysplasia Ossificans Progressiva

Abstract

Methods for treating Fibrodysplasia Ossificans Progressiva (FOP) are provided. Such methods involve administering to a subject having FOP an effective regime of an activin receptor type 2A (ACVR2A) and/or an activin receptor type 2B (ACVR2B) antagonist or an activin receptor type 1 (ACVR1) antagonist. Antagonists include fusion proteins of one or more extracellular domains (ECDs) of ACVR2A, ACVR2B and/or ACVR1 and the Fc domain of an immunoglobulin heavy chain, and antibodies against ACVR2A, ACVR2B, ACVR1 or Activin A.

We claim: 
     
         1 . A method of treating Fibrodysplasia Ossificans Progressiva (FOP), comprising administering to a subject having FOP an effective regime of an activin receptor type 2A (ACVR2A) and/or an activin receptor type 2B (ACVR2B) antagonist. 
     
     
         2 . The method of  claim 1 , wherein the antagonist comprises an ACVR2A or ACVR2B extracellular domain. 
     
     
         3 . The method of  claim 2 , wherein the antagonist comprises an ACVR2A or ACVR2B Fc fusion protein. 
     
     
         4 . The method of  claim 3 , wherein the isotype of the Fc fusion protein is human IgG1. 
     
     
         5 . The method of  claim 2 , wherein the antagonist comprises an ACVR2A extracellular domain linked to an ACVR2B extracellular domain. 
     
     
         6 . The method of  claim 5 , wherein the antagonist further comprises an Fc domain. 
     
     
         7 . The method of  claim 6 , wherein in the antagonist comprises an ACVR2A extracellular domain fused to a first Fc domain and an ACVR2B extracellular domain fused to a second Fc domain wherein the first and second Fc domains are complexed with one another. 
     
     
         8 . The method of  claim 7 , wherein the antagonist comprises a linker between the ACVR2A and ACVR2B extracellular domains, each fused to an Fc domain. 
     
     
         9 . The method of  claim 5 , wherein the antagonist is a fusion protein comprising an ACVR2A extracellular domain, an ACVR2B extracellular domain and an Fc domain. 
     
     
         10 . The method of  claim 1 , wherein an effective regime of an ACVR2A antagonist and an ACVR2B antagonist is administered. 
     
     
         11 . The method of  claim 10 , wherein the ACVR2A antagonist is an ACVR2A Fc fusion protein and the ACVR2B antagonist is an ACVR2B Fc fusion protein. 
     
     
         12 . The method of  claim 1 , wherein the antagonist is an antibody to ACVR2A or ACVR2B. 
     
     
         13 . The method of  claim 1 , wherein the subject does not have and is not at risk of type II diabetes, muscular dystrophy, amyotrophic lateral sclerosis (ALS) or osteoporosis. 
     
     
         14 . A method of treating Fibrodysplasia Ossificans Progressiva (FOP), comprising administering to a subject having FOP an effective regime of an activin receptor type 1 (ACVR1) antagonist. 
     
     
         15 . The method of  claim 14 , wherein the antagonist comprises an ACVR1 extracellular domain. 
     
     
         16 . The method of  claim 15 , wherein the antagonist comprises an ACVR1 fusion protein. 
     
     
         17 . The method of  claim 16 , wherein the isotype of the Fc fusion protein is human IgG1. 
     
     
         18 . The method of  claim 14 , wherein the antagonist is an antibody to ACVR1. 
     
     
         19 . A method of treating Fibrodysplasia Ossificans Progressiva (FOP), comprising administering to a subject having FOP an effective regime of an activin receptor type 2A (ACVR2A) and/or an activin receptor type 2B (ACVR2B) antagonist in combination with an activin receptor type 1 (ACVR1) antagonist. 
     
     
         20 . The method of  claim 19 , wherein the antagonist comprises an ACVR1, ACVR2A and/or ACVR2B extracellular domain. 
     
     
         21 . The method of  claim 20 , wherein the antagonist comprises an ACVR1, ACVR2A and/or ACVR2B Fc fusion protein. 
     
     
         22 . The method of  claim 21 , wherein the isotype of the Fc fusion protein is human IgG1. 
     
     
         23 . The method of  claim 19 , wherein the antagonist is an antibody to ACVR1, ACVR2A and/or ACVR2B. 
     
     
         24 . A method of treating Fibrodysplasia Ossificans Progressiva (FOP), comprising administering to a subject having FOP an effective regime of an antibody against Activin A. 
     
     
         25 . The method of  claim 24 , wherein the antibody competes for binding with antibody comprising the heavy and light chain variable regions of the antibody designated H4H10446P, H4H10430P or A1. 
     
     
         26 . The method of  claim 24 , wherein the antibody comprises the heavy and light chain variable regions of the antibody designated H4H10446P, H4H10430P or A1. 
     
     
         27 . The method of  claim 24 , wherein the antibody is chimeric, veneered, humanized or human antibody. 
     
     
         28 . The method of  claim 24  wherein the antibody is an intact antibody. 
     
     
         29 . The method of  claim 24 , wherein the antibody is a human kappa IgG1 antibody. 
     
     
         30 . The method of  claim 25 , wherein the antibody is a human kappa IgG1 antibody. 
     
     
         31 . The method of  claim 26 , wherein the antibody is a human kappa IgG1 antibody. 
     
     
         32 . The method of  claim 27 , wherein the antibody is a human kappa IgG1 antibody. 
     
     
         33 . The method of  claim 28 , wherein the antibody is a human kappa IgG1 antibody.