Methods for treating myocardial infarction comprising administering sonic hedgehog
The present invention relates to methods and pharmaceutical compositions for cardioprotection of subjects who experienced a myocardial infarction. In particular, the present invention relates to a ligand of the sonic hedgehog signaling pathway for use in the cardioprotection of a subject who experienced a myocardial infarction.
1. A method for reducing infarct size and reperfusion arrhythmias in a patient in need thereof, said patient having had a myocardial infarction, comprising the steps of
i) restoring blood supply in cardiac ischemic tissue of the patient, and
ii) inducing cardioprotection by administering to the patient a therapeutically effective amount of a ligand of the sonic hedgehog signaling pathway,
wherein the step of inducing cardioprotection causes a reduction in infarct size and reperfusion arrhythmias in the patient,
wherein the ligand of the sonic hedgehog signaling pathway is a sonic hedgehog polypeptide comprising a signaling domain of a hedgehog polypeptide,
and wherein the signaling domain of the hedgehog polypeptide comprises a sequence having at least 90% identity with a sequence ranging from an amino acid residue at position 1 to an amino acid residue at position 197 in SEQ ID NO:1.
2. The method of claim 1 wherein the sonic hedgehog polypeptide is a soluble polypeptide.
3. The method of claim 1 wherein the sonic hedgehog polypeptide comprises the sequence ranging from the amino acid residue at position 1 to the amino acid residue at position 197 in SEQ ID NO:1 or a function conservative variant of said sequence.
4. The method of claim 1 wherein the sonic hedgehog polypeptide is fused to a Fc portion of an antibody.
5. The method of claim 1 wherein the sonic hedgehog polypeptide is carried by a microparticle.
6. The method of claim 1 wherein steps i) and ii) are performed sequentially or concomitantly.
7. The method of claim 1 wherein the therapeutically effective amount of the ligand of the sonic hedgehog signaling pathway is administered prior to and/or at the time of reperfusion injury.
8. The method of claim 1 wherein the ligand of the sonic hedgehog signaling pathway is administered by infusion into the bloodstream.
9. The method of claim 1 wherein the ligand is capable of activating i) the Patched-Smoothened complex or ii) the ATP-dependent potassium current (IKATP), in adult cardiomyocytes.
10. The method of claim 1 , wherein the percentage of identity is at least 95%.
11. The method of claim 1 , wherein the percentage of identity is at least 96%.
12. The method of claim 1 , wherein the percentage of identity is at least 97%.
13. The method of claim 1 , wherein the percentage of identity is at least 98%.
14. The method of claim 1 , wherein the percentage of identity is at least 99%.
15. The method of claim 1 , wherein the percentage of identity is 100%.
16. The method of claim 1 , wherein the ligand of the sonic hedgehog signaling pathway is a function conservative variant of the sonic hedgehog polypeptide.