Use of the Insulin-Like-Growth Factor 1 Splice Variant MGF for the Prevention of Myocardial Damage

Abstract

The invention relates to the use of a Mechano Growth Factor (MGF) polypeptide or a polynucleotide encoding an MGF polypeptide in the manufacture of a medicament for the prevention or limitation of myocardial damage in response to ischemia or mechanical overload of the heart by preventing or limiting apoptosis in the myocardium.

What is claimed is: 
     
         1 . A method for limiting myocardial damage in response to a heart attack, comprising:
 administering to a subject in need thereof a polynucleotide encoding a Mechano Growth Factor (MGF) polypeptide in an amount effective to limit myocardial apoptosis,   wherein the polynucleotide encoding a MGF polypeptide encodes:
 (a) an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4; or 
 (b) an amino acid sequence selected from the group consisting of the amino acid sequence encoded by exons 5 and 6 of SEQ ID NO: 1; and the amino acid sequence encoded by exons 4, 5 and 6 of SEQ ID NO:3. 
   
     
     
         2 . The method of  claim 1 , wherein the MGF polypeptide is unglycosylated. 
     
     
         3 . The method of  claim 1 , wherein the amino acid sequence encoded by exons 5 and 6 is the amino acid sequence of amino acids 87-110 of SEQ ID NO:2 or amino acids 87-111 of SEQ ID NO:4. 
     
     
         4 . The method of  claim 1 , wherein the MGF polypeptide induces a hypertrophic phenotype in cardiac muscle cells. 
     
     
         5 . The method of  claim 1 , wherein the polynucleotide encoding an MGF polypeptide is formulated for intramuscular administration. 
     
     
         6 . The method of  claim 1 , wherein the polynucleotide encoding an MGF polypeptide is administered within 5 hours of the heart attack. 
     
     
         7 . The method of  claim 1 , wherein the polynucleotide encoding an MGF polypeptide is administered within 2 hours of the heart attack. 
     
     
         8 . The method of  claim 1 , wherein the polynucleotide encoding an MGF polypeptide is administered within 60 minutes of the heart attack. 
     
     
         9 . The method of  claim 1 , wherein the polynucleotide encoding an MGF polypeptide is administered within 30 minutes, 15 minutes, 10 minutes, or 5 minutes of the heart attack. 
     
     
         10 . The method of  claim 1 , wherein the polynucleotide encoding an MGF polypeptide is contained in a vector. 
     
     
         11 . The method of  claim 10 , wherein the vector is a plasmid or a disarmed viral vector.