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