Delivery of therapeutic agents by a collagen binding protein
Methods of delivering therapeutic agents by administering compositions including a bacterial collagen-binding polypeptide segment linked to the therapeutic agent to subjects in need of treatment with the therapeutic agent are provided. Methods of treating hyperparathyroidism, and hair loss using compositions comprising a collagen binding polypeptide and a PTH/PTHrP receptor agonist are provided. In addition, methods of reducing hair regrowth by administering a composition including a collagen binding polypeptide and a PTH/PTHrP receptor antagonist are provided.
1. A method of treating hyperparathyroidism comprising administering a composition comprising a bacterial collagen-binding polypeptide segment linked to a PTH/PTHrP receptor agonist to a subject in need of treatment for hyperparathyroidism, wherein the bacterial collagen-binding polypeptide segment comprises a collagen-binding polypeptide derived from an M9 peptidase selected from the group consisting of: SEQ ID NOs: 13-34, a fragment of at least 8 consecutive amino acids of SEQ ID NOs: 13-34, residues 34-158 of SEQ ID NO: 1, a fragment of at least 8 consecutive amino acids from residues 34-158 of SEQ ID NO: 1, a peptide that is at least 90% identical to residues 34-158 of SEQ ID NO: 1, and a peptide that is at least 90% identical to SEQ ID NOs: 13-34 and wherein the PTH/PTHrP receptor agonist comprises residues 1-33 of SEQ ID NO: 1, PTH (SEQ ID NO: 7), residues 1-14 of SEQ ID NO: 7, residues 1-34 of SEQ ID NO: 7, residues 1-7 of SEQ ID NO: 7 or a fragment of at least 8 consecutive amino acids from residues 1-34 of SEQ ID NO: 7.
2. The method of claim 1 , wherein the composition is administered intramuscularly, intradermally, intravenously, subcutaneously, intraperitoneally, topically, orally, parenteral, or intranasally.
3. The method of claim 1 , wherein the bacterial collagen-binding polypeptide segment comprises residues 34-158 of SEQ ID NO: 1, or one of SEQ ID NOs: 13-34.
4. The method of claim 1 , wherein the PTH/PTHrP receptor agonist comprises residues 1-33 of SEQ ID NO: 1.
5. The method of claim 1 , wherein the PTH/PTHrP receptor agonist is a polypeptide and the N-terminus of the collagen-binding polypeptide segment is linked directly or through a linker polypeptide segment to the C-terminus of the PTH/PTHrP receptor agonist polypeptide.
6. The method of claim 1 , wherein the collagen-binding polypeptide segment and the therapeutic agent are chemically cross-linked to each other or are polypeptide portions of a fusion protein.
7. The method of claim 1 , wherein the composition has at least 50% greater activity in the subject than PTH(1-34) administered alone.
8. The method of claim 1 , wherein the subject is a human.
9. The method of claim 1 , wherein the composition is administered in aqueous solution at pH below about 5.0.
10. The method of claim 1 , wherein the composition is administered in aqueous solution at pH above about 6.0.
11. The method of claim 1 , wherein the composition has at least 50% greater activity in the subject than the PTH/PTHrP receptor agonist administered alone.