PHARMACEUTICAL COMPOSITION FOR TREATING BONE DISEASES WHICH COMPRISES PROTEIN COMPRISING Frizzled1, Frizzled2 OR Frizzled7 EXTRACELLULAR CYSTEINE-RICH DOMAIN

Abstract

This invention relates to a pharmaceutical composition for treatment of a bone disease comprising, as an active ingredient, a protein comprising an extracellular cysteine-rich domain, which is from the Frizzled receptor selected from the group consisting of mammalian animal-derived Frizzled 1, Frizzled 2, and Frizzled 7 and has activity of increasing bone mass, bone density, and/or bone strength, or a mutant of such domain having sequence identity of 85% or higher to the amino acid sequence of the domain and having activity of increasing bone mass, bone density, and/or bone strength, or a vector comprising a nucleic acid encoding the protein.

1 . A pharmaceutical composition for treating a bone disease comprising, as an active ingredient, a protein comprising an extracellular cysteine-rich domain, which is from a Frizzled receptor selected from the group consisting of mammalian animal-derived Frizzled 1, Frizzled 2, and Frizzled 7 and has activity of increasing bone mass, bone density, and/or bone strength, or a mutant of the domain having sequence identity of 85% or higher to the amino acid sequence of the domain and having activity of increasing bone mass, bone density, and/or bone strength, or a vector comprising a nucleic acid encoding the protein. 
     
     
         2 . The composition according to  claim 1 , wherein the protein is a fusion protein of the extracellular cysteine-rich domain or a mutant thereof and the mammalian animal-derived immunoglobulin Fc protein or a mutant thereof, and the nucleic acid encoding the protein is a nucleic acid encoding the fusion protein. 
     
     
         3 . The composition according to  claim 1 , wherein the protein is chemically modified. 
     
     
         4 . The composition according to  claim 3 , wherein the chemical modification is a binding of one or a plurality of polyethylene glycol molecules. 
     
     
         5 . The composition according to  claim 3 , wherein the chemical modification is a binding of a sugar chain. 
     
     
         6 . The composition according to  claim 1 , wherein the protein is a fragment of an extracellular region protein of the Frizzled receptor, which fragment comprises the extracellular cysteine-rich domain. 
     
     
         7 . The composition according to  claim 1 , wherein the protein is a recombinant protein. 
     
     
         8 . The composition according to  claim 1 , wherein the extracellular cysteine-rich domain comprises an amino acid sequence comprising at least the amino acid sequence spanning from the 1st cysteine residue on the N-terminal side to the 10th cysteine residue in the amino acid sequence of the extracellular region protein of the Frizzled receptor. 
     
     
         9 . The composition according to  claim 6 , wherein the extracellular region protein comprises the amino acid sequence of SEQ ID NO: 19, 20, 22, 23, or 25. 
     
     
         10 . The composition according to  claim 1 , wherein the protein comprising the extracellular cysteine-rich domain comprises a protein comprising the amino acid sequence spanning from the 1st cysteine residue on the N-terminal side to the 10th cysteine residue as shown in SEQ ID NO: 21, 24, or 26. 
     
     
         11 . The composition according to  claim 1 , wherein the nucleic acid encoding a protein comprising the extracellular cysteine-rich domain comprises a nucleotide sequence as shown in any of SEQ ID NOs: 44 to 49. 
     
     
         12 . The composition according to  claim 2 , wherein the Fc protein comprises the amino acid sequence of SEQ ID NO: 4. 
     
     
         13 . The composition according to  claim 2 , wherein the nucleic acid encoding the Fc protein comprises the nucleotide sequence of SEQ ID NO: 3. 
     
     
         14 . The composition according to  claim 2 , wherein the fusion protein comprises the amino acid sequence as shown in any of SEQ ID NOs: 27 to 31. 
     
     
         15 . The composition according to  claim 2 , wherein the nucleic acid encoding the fusion protein comprises the nucleotide sequence as shown in any of SEQ ID NOs: 38 to 43. 
     
     
         16 . The composition according to  claim 1 , wherein the mammalian animal is a human. 
     
     
         17 . The composition according to  claim 1 , wherein the bone disease is accompanied with lowering of bone mass, bone density and/or bone strength. 
     
     
         18 . A method for treating a bone disease comprising administering the composition according to  claim 1  to a mammalian animal. 
     
     
         19 . The method according to  claim 18 , wherein the mammalian animal is a human. 
     
     
         20 . The method according to  claim 18 , wherein the bone disease is accompanied with lowering of bone mass, bone density and/or bone strength. 
     
     
         21 . The method according to  claim 18 , wherein the composition is simultaneously or continuously administered in combination with another therapeutic agent for bone disease.