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 - 45 . (canceled)  
     
     
         46 . An isolated peptide selected from the group consisting of: 
 a) a peptide consisting of an amino acid sequence that is at least 70% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19, wherein the peptide promotes myoblast differentiation;    b) a peptide consisting 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 promotes myoblast differentiation;    c) a peptide consisting of an amino acid sequence that differs from SEQ ID NO:16 by at least one substitution, deletion or insertion of an amino acid residue at a position of SEQ ID NO:16 selected from the group consisting of: 1, 2, 5, 6, 9, 10, 11, 12, 13 and 14, wherein the peptide promotes myoblast differentiation;    d) a peptide consisting of an amino acid sequence that differs from SEQ ID NO:17 by at least one substitution, deletion or insertion of an amino acid residue at a position of SEQ ID NO:17 selected from the group consisting of: 1, 2, 5, 6, 9, 10, 11, 12, and 16, wherein the peptide promotes myoblast differentiation;    e) a peptide consisting of an amino acid sequence that differs from SEQ ID NO:18 by at least one substitution, deletion or insertion of an amino acid residue at a position of SEQ ID NO:18 selected from the group consisting of: 1, 2, 5, 6, 9, 10, 11, 12, 13 and 14, wherein the peptide promotes myoblast differentiation; and    f) a peptide consisting of an amino acid sequence that differs from SEQ ID NO:19 by at least one substitution, deletion or insertion of an amino acid residue at a position of SEQ ID NO:19 selected from the group consisting of: 1, 2, 5, 6, 9, 10, 11, 12, 13 and 16, wherein the peptide promotes myoblast differentiation.    
     
     
         47 . The isolated peptide of  claim 46 , wherein the peptide consists of an amino acid sequence that is at least about 80% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19.  
     
     
         48 . The isolated peptide of  claim 46 , wherein the peptide consists of an amino acid sequence that is at least about 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19.  
     
     
         49 . The isolated peptide of  claim 46 , wherein the peptide consists of an amino acid sequence selected from the group consisting of: SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19.  
     
     
         50 . The isolated peptide of  claim 46 , wherein the peptide comprises a modification selected from the group consisting of methylation, farnesylation, carboxymethylation, geranyl geranylation, glycosylation, phosphorylation, acetylation, myristoylation, prenylation, palmitation, amidation, and complexing with a lipid carrier, or any combination thereof.  
     
     
         51 . A composition comprising the isolated peptide of  claim 46  and a pharmaceutically acceptable carrier.  
     
     
         52 . An isolated nucleic acid molecule comprising a nucleic acid sequence encoding the peptide of  claim 46 .  
     
     
         53 . A recombinant nucleic acid molecule comprising a nucleic acid molecule as set forth in  claim 52 , operatively linked to a recombinant vector.  
     
     
         54 . A method to promote myoblast differentiation, comprising administering to a myoblast stem cell the isolated peptide of  claim 46 .  
     
     
         55 . The method of  claim 54 , further comprising administering the myoblast stem cell to a patient to treat a cardiac or muscle cell disorder.  
     
     
         56 . The method of  claim 54 , further comprising administering the myoblast stem cell to an individual to stimulate cardiac or skeletal muscle growth.  
     
     
         57 . A method to regenerate damaged, degenerated or atrophied cardiac and skeletal myocytes, comprising administering to a patient that has damaged, degenerated or atrophied cardiac or skeletal myocytes, the isolated peptide of  claim 46 , or a composition comprising the peptide.  
     
     
         58 . The method of  claim 58 , comprising contacting a population of myoblast stem cells, myoblasts, or muscle cells with the isolated peptide, and administering the cells to the patient.  
     
     
         59 . A method to stimulate cardiac or skeletal muscle growth in a mammal, comprising administering to a mammal the isolated peptide of  claim 46 , or a composition comprising the peptide.  
     
     
         60 . The method of  claim 59 , comprising contacting a population of myoblast stem cells, myoblasts, or muscle cells with the isolated peptide, and administering the cells to the patient.  
     
     
         61 . A method to treat cardiac and skeletal muscle disorders, comprising administering to a patient that has a cardiac or skeletal muscle disorder the isolated peptide of  claim 46 , or a composition comprising the peptide.  
     
     
         62 . The method of  claim 61 , wherein said disorder is selected from the group consisting of: dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy, partial lipodystrophy, axonal neuropathy, and mandibuloacral dysplasia.  
     
     
         63 . The method of  claim 61 , comprising contacting a population of myoblast stem cells, myoblasts, or muscle cells with the isolated peptide, and administering the cells to the patient.