Compositions for treating pathological calcification conditions, and methods using same
The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.
1. A method for treating a mammalian subject having a loss of function mutation in cluster of differentiation 73 (CD73), the method comprising:
administering to the mammalian subject a soluble ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) fusion polypeptide, thereby treating the mammalian subject, wherein the soluble ENPP1 fusion polypeptide comprises an enzymatically active ENPP1 polypeptide, a human IgG Fc, and a linker sequence linking the enzymatically active ENPP1 polypeptide and the human IgG Fc.
2. The method of claim 1 , wherein the mammalian subject has been diagnosed as having arterial and joint calcification disease (ACDC).
3. The method of claim 1 , wherein the mammalian subject is an infant.
4. The method of claim 1 , wherein the soluble ENPP1 fusion polypeptide is administered subcutaneously to the mammalian subject.
5. The method of claim 1 , wherein the soluble ENPP1 fusion polypeptide comprises one of:
(a) amino acid residues 93 to 925 of SEQ ID NO:16;
(b) amino acid residues 93 to 1155 of SEQ ID NO: 16;
(c) amino acid residues 23 to 852 of SEQ ID NO:18;
(d) amino acid residues 23 to 1082 of SEQ ID NO:18; or
(e) amino acid residues 23 to 1079 of SEQ ID NO:20.
6. The method of claim 5 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 925 of SEQ ID NO:16.
7. The method of claim 5 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 852 of SEQ ID NO:18.
8. The method of claim 5 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 1155 of SEQ ID NO:16.
9. The method of claim 5 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1082 of SEQ ID NO:18.
10. The method of claim 5 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1079 of SEQ ID NO:20.
11. A method for treating or ameliorating arterial and joint calcification disease (ACDC) in a mammalian subject, the method comprising administering to the mammalian subject a soluble ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) fusion polypeptide, thereby treating ACDC in the mammalian subject, wherein the soluble ENPP1 fusion polypeptide comprises an enzymatically active ENPP1 polypeptide, a human IgG Fc, and a linker sequence linking the enzymatically active ENPP1 polypeptide and the human IgG Fc.
12. The method of claim 11 , wherein the mammalian subject is an infant.
13. The method of claim 11 , wherein the soluble ENPP1 fusion polypeptide is administered subcutaneously to the mammalian subject.
14. The method of claim 11 , wherein the soluble ENPP1 fusion polypeptide comprises one of:
(a) amino acid residues 93 to 925 of SEQ ID NO:16;
(b) amino acid residues 93 to 1155 of SEQ ID NO: 16;
(c) amino acid residues 23 to 852 of SEQ ID NO:18;
(d) amino acid residues 23 to 1082 of SEQ ID NO:18; or
(e) amino acid residues 23 to 1079 of SEQ ID NO:20.
15. The method of claim 14 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 925 of SEQ ID NO:16.
16. The method of claim 14 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 852 of SEQ ID NO:18.
17. The method of claim 14 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 1155 of SEQ ID NO:16.
18. The method of claim 14 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1082 of SEQ ID NO:18.
19. The method of claim 14 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1079 of SEQ ID NO:20.
20. The method of claim 11 , wherein the mammalian subject has been determined as having a loss of function mutation in CD73.