Treatment for insulin dependent diabetes

Abstract

A method for the prevention of insulin dependent (type I) diabetes. The method comprises administration of an antibody, polypeptide or other molecule recognizing VLA-4.

1 . A method for the prevention of insulin dependent (type I) diabetes comprising administering to a prediabetic individual a composition comprising an anti-VLA-4 antibody.  
     
     
         2 . A method according to  claim 1 , wherein the anti-VLA-4 antibody selected from the group consisting of HP1/2, HP2/1, HP2/4, L25, and P4C2.  
     
     
         3 . A method according to  claim 1 , wherein the anti-VLA-4 antibody is HP1/2, or a fragment thereof, capable of binding to VLA-4.  
     
     
         4 . A method according to  claim 1 , wherein the anti-VLA-4 antibody is a humanized HP1/2 antibody, or a fragment thereof, capable of binding to VLA-4.  
     
     
         5 . A method according to  claim 1 , wherein the composition is administered at a dosage so as to provide from about 0.1 to about 10 mg/kg, based on the weight of the prediabetic individual.  
     
     
         6 . A method according to  claim 1 , wherein the composition is administered in an amount effective to coat VLA-4-positive cells in the peripheral blood for a period of 1-14 days.  
     
     
         7 . A method according to  claim 1 , wherein the composition is administered in an amount effective to provide a plasma level of antibody in the prediabetic individual of at least 1 μg/ml.  
     
     
         8 . A method according to  claim 1 , wherein the composition is administered prior to the development of overt diabetes, as measured by a serum glucose level of less than about 250 mg/dL.  
     
     
         9 . A method according to  claim 1 , wherein the prediabetic individual is a human.  
     
     
         10 . A method for the treatment of diabetes comprising administering to a mammal with a susceptibility to diabetes, an antibody, a recombinant antibody, a chimeric antibody, fragments of such antibodies, a polypeptide or a small molecule capable of binding to the α 4  subunit of VLA-4, or combinations of any of the foregoing, in an amount effective to provide inhibition of onset of diabetes.  
     
     
         11 . A method according to  claim 10 , wherein the antibody, polypeptide or molecule is selected from monoclonal antibody HP1/2; Fab, Fab′, F(ab′) 2  or F(v) fragments of such antibody; soluble VCAM-1 or fibronectin polypeptides; or small molecules that bind to the VCAM-1 or fibronectin binding domain of VLA-4.  
     
     
         12 . A method according to  claim 11 , wherein the soluble VCAM-1 polypeptides comprise a VCAM-IgG fusion.  
     
     
         13 . A method according to  claim 11 , wherein the composition is administered in an amount effective to provide a plasma level of soluble VCAM-1 polypeptides in the mammal of at least 10-20 μg/ml over a period of 1-14 days.  
     
     
         14 . A method according to  claim 11 , wherein the soluble VCAM-1 polypeptides comprise VCAM 2D-IgG.  
     
     
         15 . A method according to  claim 10 , wherein the composition comprises a plurality of anti-VLA-4 monoclonal antibodies or VLA-4-binding fragments thereof.  
     
     
         16 . A method according to  claim 10 , wherein, the composition is administered at a dosage so as to provide from about 0.1 to about 10 mg/kg of antibody, antibody fragment, polypeptide or small molecule, based on the weight of the susceptible mammal.  
     
     
         17 . A method according to  claim 10 , wherein the composition is administered in an amount effective to coat VLA-4-positive cells in the peripheral blood for a period of 1-14 days.  
     
     
         18 . A method according to  claim 10 , wherein the composition is administered in an amount effective to provide a plasma level of antibody or antibody fragement in the mammal of at least 1 μg/ml over a period of 1-14 days.  
     
     
         19 . A method according to  claim 10 , wherein the composition is administered in an amount effective to provide a dosage of small molecule of about 0.1-10 mg/kg body wieght/day over a period of 1-14 days.  
     
     
         20 . A pharmaceutical composition effective to provide inhibition of onset of diabetes consisting essentially of a monoclonal antibody recognizing VLA-4 in a pharmaceutically acceptable carrier.  
     
     
         21 . A chimeric molecule comprising: 
 a VLA-4 targeting moiety capable of binding to VLA-4 antigen on the surface of VLA-4 bearing cells and a toxin moiety.    
     
     
         22 . The molecule of  claim 21 , wherein the VLA-4 targeting moiety comprises a portion of VCAM.  
     
     
         23 . A method of treating a subject at risk for a disorder characterized by the presence of activated VLA-4 comprising administering to the subject the chimeric molecule of claims  21 .  
     
     
         24 . The method of  claim 23 , wherein said disorder is diabetes.