Methods and compositions for preventing or treating tissue calcification
The invention provides methods and compositions for preventing or treating (e.g., slowing the progression of, arresting, and/or reversing) tissue calcification 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 (e.g., slowing the progression of, arresting, and/or reversing) tissue calcification in a subject with diabetes, chronic kidney disease, end stage renal failure, or a subject undergoing hemodialysis and/or receiving anticoagulant therapy. The invention further provides methods and compositions for reducing one or more symptoms of chronic obstructive pulmonary disorder (COPD), including using menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7), for preventing or treating (e.g., slowing the progression of, arresting, and/or reversing) one or more symptoms of COPD.
1. A method of treating tissue calcification in a human subject in need thereof, the method comprising administering to the human subject menaquinone-7 (MK-7) and/or menaquinol-7 (MKH2-7) thereby to treat tissue calcification in the subject, whereupon the administration of the MK-7 and/or the MKH2-7 increases a plasma level of Fetuin A relative to the plasma level of Fetuin A prior to administration, and at least one of the following:
(i) 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,
(ii) increases a ratio of a carboxylated to a non-carboxylated form of a Vitamin K-dependent protein in the subject's plasma relative to the ratio prior to administration of the MK-7 and/or MKH2-7,
(iii) increases the plasma level of osteoprotegerin relative to the plasma concentration of osteoprotegerin prior to administration of the MK-7 and/or MKH2-7, or
(iv) decreases the plasma level of D-Dimer or Highly Sensitive C Reactive Protein (hs-CRP) relative to the plasma concentration of D-Dimer or Highly Sensitive C Reactive Protein (hs-CRP) prior to administration of the MK-7 and/or MKH2-7.
2. The method of claim 1 , wherein the subject has been diagnosed as pre-diabetic.
3. The method of claim 1 , wherein the subject has chronic kidney disease.
4. The method of claim 1 , wherein the subject is undergoing hemodialysis.
5. The method of claim 1 , wherein the subject is receiving non-warfarin-based anti-coagulant therapy.
6. The method of claim 5 , wherein the anti-coagulation therapy comprises an inhibitor of Factor Xa activity or Factor IIa activity.
7. The method of claim 1 , 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.
8. The method of claim 1 , comprising administering from about 10 mg to about 100 mg of MK-7 and/or MKH2-7 to the subject per day.
9. The method of claim 1 , wherein the MK-7 and/or MKH2-7 is administered to the subject for at least 2 weeks.
10. The method of claim 1 , wherein the subject has diabetes.
11. The method of claim 1 , wherein the MK-7 and/or MKH2-7 is administered to the subject for at least 6 weeks.
12. The method of claim 4 , wherein the MK-7 and/or MKH2-7 is administered to the subject for a period that includes the duration of hemodialysis.
13. The method of claim 1 , wherein the MK-7 and/or MKH2-7 is administered orally.
14. The method of claim 1 , wherein the MK-7 and/or MKH2-7 is disposed within a tablet, caplet or capsule.
15. The method of claim 1 , wherein the subject has previously been exposed to warfarin-based anti-coagulation therapy.
16. The method of claim 1 , wherein the subject is receiving a statin.
17. The method of claim 16 , wherein the statin is selected from simvastatin, lovastatin, atorvastatin, pravastatin, pitavastatin, rosuvastatin, and fluvastatin.
18. The method of claim 1 , wherein the tissue calcification is vascular calcification.
19. The method of claim 1 , wherein the tissue calcification is dermal calcification.
20. The method of claim 1 , comprising administering 10, 25, 50, 75 or 100 mg of MK-7 and/or MKH2-7 to the subject per day.