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 . A method for treating a proteinuric disorder comprising administering to a patient in need thereof an a v β3 integrin inhibitor in an amount effective to reduce or eliminate the proteinuric disorder. 
     
     
         2 . The method of  claim 1  wherein the proteinuric disorder is a kidney proteinuric disorder. 
     
     
         3 . The method of  claim 2  wherein the kidney proteinuric disorder is selected from a list comprising 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 (i.e., Berger's disease), 
 IgM nephropathy, 
 Membranoproliferative glomerulonephritis, 
 Membranous nephropathy, 
 Minimal change disease, 
 Hypertensive nephrosclerosis and 
 Interstitial nephritis. 
 
     
     
         4 . The method of  claim 3  wherein the kidney proteinuric disorder is diabetic nephropathy. 
         5 . The method of  claim 2  wherein the kidney proteinuric disorder is selected from a list comprising of:
 Pre-eclampsia, 
 Eclampsia, 
 Collagen vascular diseases (e.g., systemic lupus erythematosus), 
 Dehydration, 
 Strenuous exercise, 
 Stress, 
 Benign Orthostatic (postural) proteinuria, 
 Sarcoidosis, 
 Alport's syndrome, 
 Diabetes mellitus, 
 Fabry's disease, 
 Infections (e.g., HIV, syphilis, hepatitis, post-streptococcal infection), 
 Aminoaciduria, 
 Fanconi syndrome, 
 Heavy metal ingestion, 
 Sickle cell disease, 
 Hemoglobinuria, 
 Multiple myeloma, 
 Myoglobinuria, 
 Organ rejection, 
 Ebola hemorrhagic fever and 
 Nail Patella Syndrome. 
 
     
     
         6 . The method of  claim 1  wherein the a v β3 integrin inhibitor is a αvβ3 monoclonal antibody or a peptide which contains a RGD binding sequence. 
     
     
         7 . The method of  claim 6  wherein the avβ3 integrin inhibitor is a αvβ3 monoclonal antibody. 
     
     
         8 . The method of  claim 7  wherein the αvβ3 monoclonal antibody is anti-CD61. 
     
     
         9 . The method of  claim 1  wherein the avβ3 integrin inhibitor is a peptide which contains a RGD binding sequence. 
     
     
         10 . The method of  claim 9  wherein the peptide which contains a RGD binding sequence is cyclo-[Arg-Gly-Asp-D-Phe-Val]. 
     
     
         11 . The method of  claim 1  wherein the avβ3 integrin inhibitors is a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.