Methods of diagnosing muscle damage

Abstract

A method for assessing muscle damage in a biological sample obtained from a subject is disclosed. The method involves obtaining a biological sample from a subject being assessed for muscle damage, and evaluating the sample for the presence or absence of a myofilament protein modification product. The method can also be used to assess the extent and/or type of muscle damage in a subject by studying the profile of myofilament protein modification products detected in the sample taken from the subject. The invention further provides a method for screening for an agent which modulates the level of a myofilament protein modification product present in a biological sample or for a calcium sensitizing agent. The invention is applicable to cardiac muscle and skeletal muscle.

1 - 52 . (canceled)  
     
     
         53 : A method for assessing skeletal muscle damage in a subject, comprising: 
 detecting the presence or absence or measuring the amount of skeletal troponin T (TnT) protein and/or skeletal TnT post-translational modification product in a biological sample obtained from a subject being assessed for skeletal muscle damage;    wherein the presence or amount of the skeletal TnT protein and/or skeletal TnT post-translational modification product in the biological sample is associated with skeletal muscle damage.    
     
     
         54 : The method of  claim 53 , wherein the skeletal TnT protein comprises fast skeletal TnT.  
     
     
         55 : The method of  claim 53 , wherein the skeletal TnT protein comprises slow skeletal TnT.  
     
     
         56 : The method of  claim 53 , wherein the skeletal TnT post-translational modification product comprises fast skeletal TnT.  
     
     
         57 : The method of  claim 56 , wherein the skeletal TnT post-translational modification product comprises a fast skeletal TnT fragment.  
     
     
         58 : The method of  claim 53 , wherein the skeletal TnT post-translational modification product comprises slow skeletal TnT.  
     
     
         59 : The method of  claim 58 , wherein the skeletal TnT post-translational modification product comprises a slow skeletal TnT fragment.  
     
     
         60 : The method of  claim 53 , wherein the skeletal TnT post-translational modification product comprises a skeletal TnT complex.  
     
     
         61 : The method of  claim 60 , wherein the skeletal TnT complex comprises a covalent complex.  
     
     
         62 : The method of  claim 60 , wherein the skeletal TnT complex comprises a non-covalent complex.  
     
     
         63 : The method of  claim 53 , wherein the presence or absence or the amount of skeletal TnT protein and/or skeletal TnT post-translational modification product in the biological sample is detected or measured by: 
 combining the biological sample with a compound that specifically binds to the skeletal TnT protein and/or skeletal TnT post-translational modification product under conditions which allow the compound to bind thereto; and    detecting the presence or measuring the amount of: 
 (i) a complex of the skeletal TnT protein and/or skeletal TnT post-translational modification product bound to the compound; or  
 (ii) unbound compound.  
   
     
     
         64 : The method of  claim 63 , wherein the compound is selected from the group consisting of an antibody, a functional fragment of an antibody, a protein, a protein fragment, a peptide, and a peptidomimetic.  
     
     
         65 : The method of  claim 63 , wherein the complex of the skeletal TnT protein and/or skeletal TnT post-translational modification product bound to the compound is immobilized on a solid phase.  
     
     
         66 : The method of  claim 63 , wherein the compound is immobilized on a solid phase.  
     
     
         67 : The method of  claim 63 , wherein detecting or measuring comprises detecting the presence or measuring the amount of a label.  
     
     
         68 : The method of  claim 67 , wherein the label provides one or more of fluorescence, luminescence, colour, and radioactivity.  
     
     
         69 : The method of  claim 67 , wherein the label comprises an enzyme which is detected by measuring enzymatic activity associated therewith.  
     
     
         70 : The method of  claim 69 , wherein the enzyme is selected from the group consisting of alkaline phosphatase, horseradish peroxidase, luciferase, beta-galactosidase, lysozyme, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and urease.  
     
     
         71 : The method of  claim 53 , wherein the presence or absence or the amount of skeletal TnT protein and/or post-translational modification product in the biological sample is detected or measured by immunoasssy.  
     
     
         72 : The method of  claim 53 , wherein the biological sample is selected from the group consisting of skeletal muscle tissue, a component of skeletal muscle tissue, blood, blood serum, blood plasma, and urine.