Compositions and Methods for Diagnosing and Treating Diseases and Disorders Associated With D-DT

Abstract

The present invention relates to the discovery that altered levels of D-DT (also known as MIF-2) are associated with disorders and diseases. Thus, the present invention relates to compositions and methods useful of the assessment, diagnosis, characterization, prevention and treatment of disorders and diseases associated with an elevated level of D-DT. The present invention also relates to compositions and methods useful of the assessment, diagnosis, characterization, prevention and treatment of disorders and diseases associated with a reduced level of D-DT.

1 . A method of diagnosing a disease or disorder in a subject in need thereof, the method comprising:
 a. determining the level of D-DT in a biological sample from the subject,   b. comparing the level of D-DT in the biological sample with a comparator control, and   diagnosing the subject with a disease or disorder when the level of D-DT in the biological sample is different than the level of D-DT of the comparator control.   
     
     
         2 . The method of  claim 1 , wherein the level of D-DT in the biological sample is elevated when compared with the comparator control. 
     
     
         3 . The method of  claim 1 , wherein the level of D-DT in the biological sample is reduced when compared with the comparator control. 
     
     
         4 . The method of  claim 1 , wherein the level of D-DT in the biological sample is determined by measuring the level of D-DT mRNA in the biological sample. 
     
     
         5 . The method of  claim 1 , wherein the level of D-DT in the biological sample is determined by measuring the level of D-DT polypeptide in the biological sample. 
     
     
         6 . The method of  claim 1 , wherein the level of D-DT in the biological sample is determined by measuring an enzymatic activity of D-DT polypeptide in the biological sample. 
     
     
         7 . The method of  claim 1 , wherein the level of D-DT in the biological sample is determined by measuring the binding of a detectable molecule to the D-DT enzyme substrate binding site. 
     
     
         8 . The method of  claim 1 , wherein the level of D-DT in the biological sample is determined by measuring the displacement of a detectable molecule from the D-DT enzyme substrate binding site. 
     
     
         9 . The method of  claim 1 , wherein the comparator control is at least one selected from the group consisting of: a positive control, a negative control, a historical control, a historical norm, or the level of a reference molecule in the biological sample. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 2 , wherein the disease or disorder is at least one selected from the group consisting of: infection, inflammatory disease, autoimmunity and cancer. 
     
     
         12 . The method of  claim 3 , wherein the disease or disorder is an ischemia-reperfusion injury. 
     
     
         13 . The method of  claim 1 , further comprising the step of treating the subject for the diagnosed disease or disorder. 
     
     
         14 . A composition comprising a D-DT inhibitor. 
     
     
         15 . The composition of  claim 14 , wherein the D-DT inhibitor is an antibody that specifically binds to D-DT. 
     
     
         16 . The composition of  claim 15 , wherein the antibody specifically binds to D-DT and does not specifically bind to MIF. 
     
     
         17 . The composition of  claim 15 , wherein the antibody specifically binds to D-DT and also specifically binds to MIF. 
     
     
         18 . The composition of  claim 15 , wherein the antibody is at least one selected from the group consisting of: a polyclonal antibody, a monoclonal antibody, an intracellular antibody, an antibody fragment, a single chain antibody (scFv), a heavy chain antibody, a synthetic antibody, a chimeric antibody, and humanized antibody. 
     
     
         19 . The composition of  claim 14 , wherein the D-DT inhibitor is an antisense nucleic acid. 
     
     
         20 . The composition of  claim 19 , wherein the antisense nucleic acid is at least one selected from the group consisting of: siRNA and miRNA. 
     
     
         21 . The composition of  claim 20 , wherein the siRNA comprises the nucleic acid sequence of SEQ ID NO: 2. 
     
     
         22 . The composition of  claim 14  wherein the D-DT inhibitor is at least one selected from the group consisting of: a chemical compound, a protein, a peptide, a peptidomemetic, a ribozyme, and a small molecule chemical compound. 
     
     
         23 . A method of treating or preventing a disease or disorder in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a composition comprising a D-DT inhibitor. 
     
     
         24 . The method of  claim 23 , wherein the D-DT inhibitor is an antibody that specifically binds to D-DT. 
     
     
         25 . The method of  claim 24 , wherein the antibody specifically binds to D-DT and does not specifically bind to MIF. 
     
     
         26 . The method of  claim 24 , wherein the antibody specifically binds to D-DT and also specifically binds to MIF. 
     
     
         27 . The method of  claim 24 , wherein the antibody is at least one selected from the group consisting of: a polyclonal antibody, a monoclonal antibody, an intracellular antibodies, an antibody fragment, a single chain antibody (scFv), a heavy chain antibody, a synthetic antibody, a chimeric antibody, and humanized antibody. 
     
     
         28 . The method of  claim 23 , wherein the D-DT inhibitor is an antisense nucleic acid. 
     
     
         29 . The method of  claim 28 , wherein the antisense nucleic acid is at least one selected from the group consisting of: siRNA and miRNA. 
     
     
         30 . The method of  claim 29 , wherein the siRNA comprises the nucleic acid sequence of SEQ ID NO: 2. 
     
     
         31 . The method of  claim 23 , wherein the D-DT inhibitor is at least one selected from the group consisting of: a chemical compound, a protein, a peptide, a peptidomemetic, a ribozyme, and a small molecule chemical compound. 
     
     
         32 . The method of  claim 23 , wherein the disease or disorder is at least one selected from the group consisting of: infection, inflammatory disease, autoimmunity and cancer. 
     
     
         33 - 44 . (canceled) 
     
     
         45 . A composition comprising a D-DT activator. 
     
     
         46 . The composition of  claim 45 , wherein the D-DT activator is at least one selected from the group consisting of: a chemical compound, a protein, a peptide, a peptidomemetic, an antisense nucleic acid, a ribozyme, or a small molecule chemical compound. 
     
     
         47 - 63 . (canceled)