Remedies for ischemia
The present invention relates to uses and methods of parathyroid hormone (PTH), preferably PTH (1-34), and/or parathyroid hormone-related peptide (PTHrP), preferably PTHrP (1-34), for recruiting stem cells into tissue suffering from ischemia, wherein said stem cells are preferably capable of repairing and/or regenerating said tissue suffering from ischemia. Also provided is the use of a combination of G-CSF or a G-CSF fragment and a DPP IV inhibitor/antagonist in the medical intervention of an ischemic disorder. Accordingly, the uses and methods of the present invention are preferably suitable for the prevention and/or treatment of ischemia. Moreover, the present invention relates to a composition comprising parathyroid hormone (PTH), preferably PTH (1-34), and/or parathyroid hormone-related peptide (PTHrP), preferably PTHrP (1-34), and/or G-CSF or a G-CSF fragment for use as a pharmaceutical composition. In a particular aspect of the invention, a DPP IV antagonist is applied in the uses, methods and/or compositions of the present invention. The DPP IV antagonist/inhibitor is preferably used in combination with G-CSF or a G-CSF fragment. Also the use of PTH alone or PTHrP alone or in combination with a DPP IV antagonist as well as the one of a combination of G-CSF or a G-CSF fragment and a DPP IV inhibitor/antagonist in the herein disclosed medical and pharmaceutical uses and methods is part of this invention.
1. A method of repairing and/or regenerating myocardial ischemic tissue in a human subject in need of such a treatment, said treatment comprising the step of administering to said subject G-CSF and a DPP IV inhibitor/antagonist in an amount that is pharmaceutically effective to repair and/or regenerate the myocardial ischemic tissue,
wherein said DPP IV inhibitor/antagonist is a small molecule that inhibits or antagonizes the physiological effect of DPP IV.
2. The method of claim 1 , wherein said DPP IV inhibitor/antagonist is selected from the group consisting of Sitagliptin, Diprotin A, Vildagliptin, Alogliptin, Saxagliptin, Linagliptin, Dutogliptin, Carmegliptin and Melogliptin.
3. The method of claim 2 , wherein the DPP IV inhibitor/antagonist is Sitagliptin.
4. The method of claim 2 , wherein said DPP IV inhibitor/antagonist is Vildagliptin.
5. The method of claim 1 , wherein said G-CSF is administered to said subject in a dosage of about 1.25 μg/kg per day to about 50 μg/kg per day and wherein said DPP IV inhibitor/antagonist is administered in a dosage of about 25 mg per day to about 500 mg per day.
6. The method of claim 5 , wherein said G-CSF is administered at a concentration of 10 to 40 μg/kg per day and said DPP IV inhibitor/antagonist is Sitagliptin and is administered at a dose of 50 to 200 mg per day.
7. The method of claim 1 , wherein said G-CSF is administered in a treatment period of about 3 days to about 7 days and said DPP IV inhibitor/antagonist is administered as a treatment period of about 10 days to about 180 days.
8. The method of claim 7 , wherein said G-CSF is administered during the treatment period of about 5 days at a concentration of 10μg/kg/d divided in two doses subcutaneously and wherein said DPP IV inhibitor/antagonist is administered at about 100 mg orally each day for about 28 days.