Methods and compositions for preventing or treating calciphylaxis
The invention provides methods and compositions for preventing or treating (e.g., slowing the progression of, arresting, and/or reversing) calciphylaxis in a subject in need thereof and, more particularly, the invention relates to methods of using menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7) for preventing or treating calciphylaxis in a subject with one or more of the following: diabetes, chronic kidney disease, end stage renal failure, and COPD or a subject undergoing hemodialysis and/or receiving anticoagulant therapy and/or statin therapy.
1. A method of treating calciphylaxis in a human subject in need thereof, the method comprising administering to the human subject at least 10 mg of a composition comprising substantially pure menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7) per day thereby to treat calciphylaxis in the subject, whereupon the administration of the MK-7 and/or MKH2-7 increases a plasma level of Fetuin A relative to the plasma level of Fetuin A prior to administration.
2. The method of claim 1 , wherein the subject has distal calciphylaxis and/or central calciphylaxis.
3. The method of claim 1 , wherein the subject has diabetes, chronic kidney disease or end stage renal disease.
4. The method of claim 3 , wherein the subject has stage 3 chronic kidney disease.
5. The method of claim 3 , wherein the subject has stage 4 chronic kidney disease.
6. The method of claim 3 , wherein the subject has stage 5 chronic kidney disease.
7. The method of claim 1 , wherein the subject is undergoing hemodialysis.
8. The method of claim 1 , wherein the subject is receiving non-warfarin-based anti-coagulant therapy.
9. The method of claim 8 , wherein the anti-coagulant therapy is oral anti-coagulation therapy.
10. The method of claim 8 , wherein the anti-coagulation therapy comprises an inhibitor of Factor Xa activity or Factor IIa activity.
11. The method of claim 1 , wherein the subject has chronic obstructive pulmonary disease (COPD).
12. The method of claim 1 , wherein the subject has a calciphylaxis-related dermal lesion.
13. The method of claim 12 , wherein administration of the composition reduces the size of the dermal lesion.
14. The method of claim 1 , whereupon administration of the MK-7 and/or MKH2-7 to the subject increases the subject's serum T50 value relative to the subject's serum T50 value prior to administration of the MK-7 and/or MKH2-7.
15. The method of claim 1 , wherein administration of the MK-7 and/or MKH2-7 (a) increases a ratio of a carboxylated to a non-carboxylated of a Vitamin K dependent protein or (b) decreases an amount of a non-carboxylated Vitamin K dependent protein in plasma of the subject relative to the ratio or amount present prior to administration of the MK-7 and/or MKH2-7.
16. The method of claim 15 , wherein the Vitamin K-dependent protein is selected from Matrix Gla Protein, Growth Arrest Specific Gene 6 (Gas-6) protein, PIVKA-II protein, osteocalcin, activated Protein C, or activated Protein S.
17. The method of claim 1 , wherein upon administration of the MK-7 and/or MKH2-7 to the subject increases a plasma level of osteoprotegerin relative to the plasma level of osteoprotegerin prior to administration of the MK-7 and/or MKH2-7.
18. The method of claim 1 , wherein upon administration of the MK-7 and/or MKH2-7 to the subject decreases a plasma level of D-Dimer or Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma level of D-Dimer or Highly Sensitive C Reactive Protein (hs-CRP) prior to administration of the MK-7 and/or MKH2-7.
19. The method of claim 1 , wherein from about 10 mg to about 50 mg of MK-7 and/or MKH2-7 is administered to the subject per day.
20. The method of claim 1 , wherein 10, 25, 50, 75 or 100 mg of MK-7 and/or MKH2-7 is administered to the subject per day.
21. The method of claim 1 , wherein the composition is administered to the subject for at least 2 weeks.
22. The method of claim 1 , wherein the composition is administered daily.
23. The method of claim 1 , wherein the composition is administered orally.
24. The method of claim 1 , wherein the subject is taking calcium-based phosphate binders and/or vitamin D analogs.
25. The method of claim 1 , wherein the composition is administered to the subject for at least 6 weeks.
26. The method of claim 7 , wherein the composition is administered to the subject for a period that includes the duration of hemodialysis.
27. The method of claim 1 , wherein the composition is disposed within a tablet, caplet, or capsule.
28. The method of claim 1 , wherein the composition comprises MK-7 and/or MKH2- 7 and a pharmaceutically acceptable excipient.
29. The method of claim 1 , wherein, prior to administration of the composition, the subject has a uremic oxidative blockade.