Inhibitors of placental growth factor for the treatment of pathological angiogenesis, pathological arteriogenesis, inflammation, tumor formation and/or vascular leakage

Abstract

The present invention relates to the field of pathological angiogenesis and arteriogenesis and, in particular, to a stress-induced phenotype in a transgenic mouse (PIGF −/− ) that does not produce Placental Growth Factor (PIGF) and that demonstrates an impaired vascular endothelial growth factor (VEGF)-dependent response. PIGF deficiency has a negative influence on diverse pathological processes of angiogenesis, arteriogenesis and vascular leakage comprising ischemic retinopathy, tumor formation, pulmonary hypertension, vascular leakage (edema formation) and inflammatory disorders. The invention thus relates to molecules that can inhibit the binding of PIGF to its receptor (VEGFR-1), such as monoclonal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

1 . A method of suppressing inflammation in a mammal, comprising administering to a mammal in need of suppressing inflammation a molecule that is capable of neutralizing the activity of placental growth factor, such that said inflammation is suppressed. 
   
   
       2 . The method according to  claim 1  wherein said inflammation is an inflammatory disorder or inflammatory disease. 
   
   
       3 . A method of suppressing development of inflammation-associated edema in a mammal, comprising administering to a mammal likely to develop inflammation-associated edema a molecule that is capable of neutralizing the activity of placental growth factor, such that development of inflammation-associated edema is suppressed. 
   
   
       4 . The method according to  claim 1  wherein said molecule is an antibody or a fragment thereof capable of neutralizing the activity of placental growth factor. 
   
   
       5 . The method according to  claim 4  wherein said antibody is a monoclonal antibody. 
   
   
       6 . The method according to  claims 4  or  5  wherein said antibody is a human or humanized antibody. 
   
   
       7 . The method according to  claim 4  wherein said antibody fragment is a Fab, F(ab)′2 or scFv fragment. 
   
   
       8 . A method of reducing inflammation in a mammal, comprising administering to a mammal suffering from inflammation a molecule that inhibits the activity of placental growth factor, such that said inflammation is reduced. 
   
   
       9 . The method according to  claim 8  wherein said inflammation is an inflammatory disorder or inflammatory disease. 
   
   
       10 . A method of reducing development of inflammation-associated edema in a mammal, comprising administering to a mammal likely to develop inflammation-associated edema a molecule that inhibits the activity of placental growth factor, such that development of inflammation-associated edema is reduced. 
   
   
       11 . The method according to  claim 8  wherein said molecule is an antibody or a fragment thereof capable of inhibits the activity of placental growth factor. 
   
   
       12 . The method according to  claim 11  wherein said antibody is a monoclonal antibody. 
   
   
       13 . The method according to  claims 11  or  12  wherein said antibody is a human or humanized antibody. 
   
   
       14 . The method according to  claim 11  wherein said antibody fragment is a Fab, F(ab)′2 or scFv fragment.