Use of the insulin-like-growth factor I 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.

1 . A method of preventing or limiting myocardial damage in response to ischemia or mechanical overload of the heart, comprising administering to a subject that has suffered said ischemia or mechanical overload an effective amount of a Mechano Growth Factor (MGF) polypeptide or a polynucleotide encoding an MGF polypeptide.  
     
     
         2 . The method of  claim 1  wherein said ischemia is temporary ischemia or said mechanical overload is a temporary overload.  
     
     
         3 . The method of  claim 1  wherein said polypeptide or polynucleotide are administered in response to a heart attack.  
     
     
         4 . The method of  claim 1  wherein the MGF polypeptide is unglycosylated.  
     
     
         5 . The method of  claim 1  wherein said MGF polypeptide comprises, or said polynucleotide encodes, a sequence comprising: (a) the sequence of Human MGF (SEQ ID NO. 2, Rat MGF (SEQ ID NO. 4) or Rabbit MGF (SEQ ID NO. 6); (b) a sequence having 70% or greater identity to a sequence of (a); or (c) a sequence comprising the amino acids encoded wholly or partly by exons 5 and 6, 4, 5 and 6 or 3, 4, 5 and 6 of human, rat or rabbit MGF DNA of SEQ ID NO. 1, 3 or 5; or a sequence having 70% or greater identity thereto.  
     
     
         6 . The method of  claim 5  wherein said MGF polypeptide has the ability to induce a hypertrophic phenotype in cardiac muscle cells.  
     
     
         7 . The method of  claim 5  wherein said administration is intramuscular.  
     
     
         8 . The method of  claim 5  wherein said polynucleotide is contained within a vector.  
     
     
         9 . The method of  claim 8  wherein the vector is a plasmid or a disarmed viral vector.  
     
     
         10 . A product comprising an MGF polypeptide and a polynucleotide encoding an MGF polypeptide for simultaneous, separate or sequential use in the prevention of myocardial damage in response to ischemia or mechanical overload of the heart.  
     
     
         11 . The product of  claim 10  wherein said MGF polypeptide is for administration before said polynucleotide.  
     
     
         12 . The method of  claim 5  wherein both an MGF polypeptide and a polynucleotide encoding an MGF polypeptide are administered to said subject.  
     
     
         13 . The method of  claim 12  wherein said MGF polypeptide is administered before said polynucleotide.  
     
     
         14 . The method of  claim 5  wherein said ischemia is temporary ischemia or said mechanical overload is a temporary overload.  
     
     
         15 . The method of  claim 5  wherein said polypeptide or polynucleotide are administered in response to a heart attack.  
     
     
         16 . The method of  claim 5  wherein said MGF polypeptide is unglycosylated.