Product and Methods for Diagnosis and Therapy for Cardiac and Skeletal Muscle Disorders

Abstract

Disclosed are products and methods to promote myoblast activation and cardiac and skeletal muscle growth or regeneration, and to treat heart and skeletal muscle diseases, based on the identification of cellular processes affected by prelamin A processing.

1 . An isolated peptide selected from the group consisting of:
 a. a peptide consisting essentially of SEQ ID NO:2;   b. a biologically active fragment of SEQ ID NO:2;   c. a peptide consisting essentially of an amino acid sequence that is at least about 70% identical to SEQ ID NO:2, wherein the peptide has the biological activity of SEQ ID NO:2; and   d. a peptide consisting essentially of an amino acid sequence that differs from SEQ ID NO:2 by at least one substitution, deletion or insertion of an amino acid residue at a position of SEQ ID NO:2 selected from the group consisting of: 1, 2, 5, 6, 9, 10, 11, 12, 13 and 14, wherein the peptide has the biological activity of SEQ ID NO:2.   
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The isolated peptide of  claim 1 , wherein the peptide consists essentially of an amino acid sequence that differs from SEQ ID NO:2 by at least one substitution, deletion or insertion of an amino acid residue at a position of SEQ ID NO:2 selected from the group consisting of: 1, 2, 5, 6, 9, 10, 11 and 12. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The isolated peptide of  claim 1 , wherein the peptide comprises a modification selected from the group consisting of farnesylation, carboxymethylation, geranyl-geranylation, and complexing with a lipid carrier. 
     
     
         8 - 15 . (canceled) 
     
     
         16 . A therapeutic composition for promoting myoblast activation and growth or regeneration of cardiac or skeletal muscle comprising an isolated peptide consisting essentially of a carrier for therapeutic agents for the treatment of cardiac or skeletal muscle disorders, consisting essentially of an isolated fragment of SEQ ID NO:4 with inter-nuclear transport domain biological activity, or a biologically active homologue thereof, operatively linked to a therapeutic agent for promoting myoblast activation and growth or regeneration of cardiac or skeletal muscle, wherein the therapeutic agent is a protein selected from the group consisting of:
 a. a protein comprising an amino acid sequence represented by SEQ ID NO:4:,   b. a protein comprising biologically active fragment of SEQ ID NO:4; and   c. a protein comprising an amino acid sequence that is at least about 70% identical to SEQ ID NO:4, wherein the protein has prelamin A or lamin A biological activity;
 wherein the protein is chemically or recombinantly attached to a therapeutic agent that increases the half-life of the protein in cardiac or skeletal muscle tissue. 
   
     
     
         17 - 41 . (canceled) 
     
     
         42 . A method to promote myoblast activation and regeneration of damaged, degenerated or atrophied cardiac and skeletal myocytes, to stimulate cardiac or skeletal muscle growth in a mammal, or to treat cardiac and skeletal muscle disorders, comprising administering to a patient that has damaged, degenerated or atrophied cardiac or skeletal myocytes the isolated peptide of  claim 1 , or a composition comprising the peptide. 
     
     
         43 - 45 . (canceled)