Methods for treating pseudoxanthoma elasticum (PXE)
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 with a loss of function mutation in an ABCC6 gene in the mammalian subject's genome,
the method comprising administering to the mammalian subject a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-1 (ENPP1) fusion polypeptide, thereby treating the mammalian subject with a loss of function mutation in an ABCC6 gene in the mammalian subject's genome,
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, and
wherein the soluble ENPP1 fusion polypeptide comprises:
(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;
(e) amino acid residues 23 to 1079 of SEQ ID NO:20; or
(f) the linker amino sequence LIN (SEQ ID NO:28).
2. The method of claim 1 , wherein the mammalian subject has been diagnosed as having Pseudoxanthoma elasticum (PXE).
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 amino acid residues 93 to 925 of SEQ ID NO:16.
6. The method of claim 1 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 852 of SEQ ID NO:18.
7. The method of claim 1 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 1155 of SEQ ID NO:16.
8. The method of claim 1 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1082 of SEQ ID NO:18.
9. The method of claim 1 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1079 of SEQ ID NO:20.
10. A method for treating Pseudoxanthoma elasticum (PXE) in a mammalian subject,
the method comprising administering to the mammalian subject a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-1 (ENPP1) fusion polypeptide, thereby treating PXE 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, and
wherein the soluble ENPP1 fusion polypeptide comprises:
(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;
(e) amino acid residues 23 to 1079 of SEQ ID NO:20; or
(f) the linker amino sequence LIN (SEQ ID NO:28).
11. The method of claim 10 , wherein the mammalian subject is an infant.
12. The method of claim 10 , wherein the soluble ENPP1 fusion polypeptide is administered subcutaneously to the mammalian subject.
13. The method of claim 10 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 925 of SEQ ID NO:16.
14. The method of claim 10 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 852 of SEQ ID NO:18.
15. The method of claim 10 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 1155 of SEQ ID NO:16.
16. The method of claim 10 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1082 of SEQ ID NO:18.
17. The method of claim 10 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1079 of SEQ ID NO:20.
18. The method of claim 10 , wherein the mammalian subject has been determined as having a loss of function mutation in an ABCC6 gene in the mammalian subject's genome.
19. A method for treating Pseudoxanthoma elasticum (PXE) in a human subject,
the method comprising administering to the human subject a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-1 (ENPP1) fusion polypeptide, thereby treating PXE in the human 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, and
wherein the soluble ENPP1 fusion polypeptide comprises:
(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;
(e) amino acid residues 23 to 1079 of SEQ ID NO:20; or
(f) the linker amino sequence LIN (SEQ ID NO:28).
20. The method of claim 19 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 1155 of SEQ ID NO:16.
21. The method of claim 19 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1082 of SEQ ID NO:18.
22. The method of claim 19 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1079 of SEQ ID NO:20.
23. A method for treating a human subject with a loss of function mutation in an ABCC6 gene in the human subject's genome,
the method comprising administering to the human subject a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-1 (ENPP1) fusion polypeptide, thereby treating the human subject with a loss of function mutation in an ABCC6 gene in the human subject's genome,
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, and
wherein the soluble ENPP1 fusion polypeptide comprises:
(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;
(e) amino acid residues 23 to 1079 of SEQ ID NO:20; or
(f) the linker amino sequence LIN (SEQ ID NO:28).
24. The method of claim 23 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 93 to 1155 of SEQ ID NO:16.
25. The method of claim 23 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1082 of SEQ ID NO:18.
26. The method of claim 23 , wherein the soluble ENPP1 fusion polypeptide comprises amino acid residues 23 to 1079 of SEQ ID NO:20.
27. The method of claim 1 , wherein the mammalian subject is a human.
28. The method of claim 10 , wherein the mammalian subject is a human.
29. The method of claim 19 , wherein the soluble ENPP1 fusion polypeptide is administered subcutaneously to the human subject.
30. The method of claim 23 , wherein the soluble ENPP1 fusion polypeptide is administered subcutaneously to the human subject.