Compositions for treating ectopic calcification disorders, and methods using same
The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.
1. A method of treating pathological calcification of soft tissue in a subject in need thereof,
the method comprising administering to the subject a therapeutically effective amount of a polypeptide comprising a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) polypeptide, whereby pathological calcification in the subject is treated.
2. The method of claim 1 , wherein the polypeptide is administered locally, regionally, parenterally, or systemically to the subject.
3. The method of claim 1 , wherein the polypeptide is administered to the subject in a dosage ranging from about 1 ng/kg to about 500 mg/kg of body weight.
4. The method of claim 1 , wherein the polypeptide is administered daily, or more than once per day, or every other day, or weekly, or biweekly, or monthly, to the subject.
5. The method of claim 1 , wherein the polypeptide comprises soluble human ENPP3 comprising a C-terminal domain selected from the group consisting of a human IgG Fc domain and human serum albumin.
6. The method of claim 5 , wherein the human IgG is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.
7. The method of claim 5 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs: 19, 21, and 22.
8. The method of claim 5 , wherein the extracellular domain of ENPP3 comprises amino acid residues of SEQ ID NO: 1.
9. The method of claim 5 , wherein the polypeptide is selected from the group consisting of SEQ ID NOs: 24, 25, and 26.
10. The method of claim 1 , wherein the pathological calcification of soft tissue is present in a disease selected from the group consisting of general arterial calcification of infancy (GACI), idiopathic infantile arterial calcification (IIAC), aging related hardening of arteries, progeria, pseudoxanthoma elasticum (PXE), medial wall vascular calcification (MWVC), end state renal disease (ESRD), chronic kidney disease-bone/mineral disorder (CKD-MBD), and calcific uremic arteriolopathy (CUA).
11. A method of treating pathological ossification in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polypeptide comprising a soluble ecto-nucleotide pyrophosphate/phosphodiesterase-3 (ENPP3) polypeptide, whereby pathological ossification in the subject is treated.
12. The method of claim 11 , wherein the pathological ossification is present in a disease selected from the group consisting of ossification of posterior longitudinal ligament (OPLL), autosomal recessive hypophosphatemia rickets type-2 (ARHR2), X-linked hypophosphatemia (XLH), age related osteopenia, and hypophosphatemic rickets.
13. The method of claim 11 , wherein the soluble ENPP3 polypeptide comprises a C-terminal domain selected from the group consisting of a human IgG Fc domain and human serum albumin.