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 composition comprising a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-1 (ENPP1) fusion polypeptide comprising an ENPP1 polypeptide which is defined by residues 23 to 852 of SEQ ID NO: 18, wherein said ENPP1 polypeptide is joined to human IgGFc, and wherein the composition can treat pathological calcification or ossification.
2. The composition of claim 1 , wherein said human IgG Fc is defined by the amino acid sequence set forth in SEQ ID NO: 26.
3. The composition of claim 1 , wherein said ENPP1 polypeptide is joined to said human IgG Fc via an amino acid linker.
4. The composition of claim 1 , wherein said soluble ENPP1 fusion polypeptide is defined by residues 23 to 1082 of SEQ ID NO: 18.
5. The composition of claim 1 , wherein said soluble ENPP1 fusion polypeptide reduces vascular calcification in vivo.
6. The composition of claim 1 , wherein said soluble ENPP1 fusion polypeptide reduces calcification of calcified heart tissue in vivo.
7. The composition of claim 1 , wherein said soluble ENPP1 fusion polypeptide reduces calcification of calcified aorta tissue in vivo.
8. The composition of claim 1 , wherein said soluble ENPP1 fusion polypeptide reduces calcification in calcified coronary artery tissue in vivo.
9. The composition of claim 1 , wherein said ENPP1 polypeptide is defined by residues 93 to 925 of SEQ ID NO: 16.
10. The composition of claim 9 , wherein said human IgG Fc is defined by the amino acid sequence set forth in SEQ ID NO: 26.
11. The composition of claim 9 , wherein said ENPP1 polypeptide is joined to said human IgG Fc via an amino acid linker.
12. The composition of claim 9 , wherein said soluble ENPP1 fusion polypeptide is defined by residues 93 to 1155 of SEQ ID NO: 16.