Methods and Compositions for the Treatment of Proteinuric Diseases

Abstract

The present invention is directed to methods of treating proteinuric diseases by the administration of avβ3 integrin inhibitors.

What is claimed is: 
     
         1 - 11 . (canceled) 
     
     
         12 . A method for treating a proteinuric disorder comprising:
 administering to a patient in need thereof, a peptide αvβ3 integrin inhibitor comprising an RGD binding sequence, in an amount effective to treat the proteinuric disorder.   
     
     
         13 . The method of  claim 12 , wherein the proteinuric disorder is a kidney proteinuric disorder. 
     
     
         14 . The method of  claim 13 , wherein the kidney proteinuric disorder is selected from the group consisting of:
 Diabetic nephropathy,   Nephrotic syndromes (i.e. intrinsic renal failure),   Nephritic syndromes,   Toxic lesions of kidneys,   Glomerular diseases, such as membranous glomerulonephritis,   Focal segmental glomerulosclerosis (FSGS),   IgA nephropathy,   IgM nephropathy,   Membranoproliferative glomerulonephritis,   Membranous nephropathy,   Minimal change disease,   Hypertensive nephrosclerosis, and   Interstitial nephritis.   
     
     
         15 . The method of  claim 14 , wherein the kidney proteinuric disorder is diabetic nephropathy. 
     
     
         16 . The method of  claim 13 , wherein the kidney proteinuric disorder is selected from the group consisting of:
 Pre-eclampsia,   Eclampsia,   Collagen vascular diseases,   Dehydration,   Strenuous exercise,   Stress,   Benign Orthostatic (postural) proteinuria,   Sarcoidosis,   Alport's syndrome,   Diabetes mellitus,   Fabry's disease,   Infections,   Aminoaciduria,   Fanconi syndrome,   Heavy metal ingestion,   Sickle cell disease,   Hemoglobinuria,   Multiple myeloma,   Myoglobinuria,   Organ rejection,   Ebola hemorrhagic fever, and   Nail Patella Syndrome.   
     
     
         17 . The method of  claim 12 , wherein the peptide that contains an RGD binding sequence is cyclo-[Arg-Gly-Asp-D-Phe-Val]. 
     
     
         18 . The method of  claim 12 , wherein the patient has proteinuria associated with podocytes exhibiting increased uPAR-induced αvβ3 integrin activation. 
     
     
         19 . The method of  claim 18 , further comprising detecting increased podocyte αvβ3 integrin activation. 
     
     
         20 . The method of  claim 19 , wherein detecting increased podocyte αvβ3 integrin activation is performed using an antibody-based assay. 
     
     
         21 . The method of  claim 12 , further comprising measuring the patient's urinary protein prior to and after the administration of the αvβ3 integrin inhibitor, wherein a reduction in the amount of urinary protein indicates that the proteinuria is reduced. 
     
     
         22 . The method of  claim 21 , wherein measuring the patient's urinary protein prior to administration of the peptide comprises detecting 150 mg or more of protein in the urine of the subject. 
     
     
         23 . The method of  claim 12 , wherein the peptide is administered to the subject intravenously.