Monomeric and Dimeric Forms of Adiponectin Receptor Fragments and Methods of Use

Abstract

Methods are disclosed for determining progression of a condition, onset of a condition, or efficacy of treatment of a condition characterized by an adipocyte imbalance in a patient. In addition, disclosed herein are methods of treating diabetes, abnormal adipocyte activity, and insulin resistance using monomeric, homodimeric, and heterodimeric forms of certain C-terminal fragments of adiponectin receptor. In addition, methods of treating abnormal adipocyte activity, treating metabolic syndrome, causing insulin secretion, increasing insulin levels, inhibiting insulin degradation enzyme, treating Alzheimer's disease, treating cardiovascular disease associated with adiponectin levels, inhibiting ADAM-17 enzyme, inhibiting a protease, treating a condition associated with TNF-alpha, and treating a condition associated with HER 2 -neu are disclosed. Compositions, dosage forms, and kits are also disclosed.

1 . A method for determining progression, onset, or efficacy of treatment of Alzheimer's disease in a patient, comprising: determining a level of a peptide in a biological fluid sample obtained from said patient; wherein said peptide is a heterodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a first homodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a second homodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a dimer of said heterodimer; a dimer of said first homodimer; or a dimer of said second homodimer; and correlating the level of said heterodimer, said homodimer, or said dimer with said progression, onset, or efficacy of treatment of Alzheimer's disease. 
     
     
         2 . The method of  claim 1 , wherein said level of peptide is determined using an immunoassay. 
     
     
         3 .- 15 . (canceled) 
     
     
         16 . A method of inhibiting insulin degradation enzyme (IDE) in a patient suffering from Alzheimer's disease, comprising: administering to said patient an effective amount of a peptide or a pharmaceutically-acceptable salt thereof; wherein said peptide is a heterodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a first homodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a second homodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a dimer of said heterodimer, a dimer of said first homodimer, or a dimer of said second homodimer. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . A method of treating Alzheimer's disease in a patient, comprising: administering to said patient an effective amount of a peptide or a pharmaceutically-acceptable salt thereof; wherein said peptide is a heterodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a first homodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:5, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a second homodimer comprising a first mer unit and a second mer unit, wherein said first mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6 and wherein said second mer unit consists of 25 amino acids and has at least about 75% identity with SEQ ID NO:6, and wherein said first mer unit and said second mer unit are linked via a disulfide bond; a dimer of said heterodimer; a dimer of said first homodimer; or a dimer of said second homodimer. 
     
     
         20 .- 44 . (canceled)