Method for modulating, regulating and/or stabilizing angiogenesis

Abstract

A method of modulating, regulating and/or stabilizing angiogenesis in a mammal in need thereof, in which the PDGF-D level or activity or both in the mammal are modulated or increased. In preferred embodiments, an active PDGF-D polypeptide, or a polynucleotide encoding an active PDGF-D is administered to the mammal, preferably at a location where angiogenesis modulation or stabilization is desired. The PDGF-D is advantageously co-administered with an angiogenic growth factor, such as a member of the VEGF family of growth factors, in particular VEGF-E. The claimed method inhibits leakage of blood vessels and is useful, inter alia, for treatment of edemas.

1 . A method for modulating, regulating or stabilizing angiogenesis in a mammal in need thereof, comprising administering an amount of a polynucleotide which encodes active PDGF-D sufficient to increase the level or activity of PDGF-D in said mammal. 
     
     
         2 - 11 . (canceled) 
     
     
         12 . The method according to claim  11 , wherein the polynucleotide encodes an active PDGF-D polypeptide comprises an amino acid sequence which is at least 95% identical to SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4. 
     
     
         13 . The method according to claim  11 , wherein an additional polynucleotide encoding an active VEGF-E polypeptide is co-administered to the mammal. 
     
     
         14 . The method according to  claim 13 , wherein additional polynucleotide encodes an active VEGF-E polypeptide comprising an amino acid sequence which is at least 95% identical to SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
         15 . The method according to  claim 14 , wherein the polynucleotide encoding the active PDGF-D polypeptide, or the additional polynucleotide encoding the active VEGF-E polypeptide, or both, are operably linked to a suitable promoter. 
     
     
         16 . The method according to  claim 14 , wherein the promoter is a tissue specific promoter. 
     
     
         17 - 21 . (canceled) 
     
     
         22 . The method according to  claim 1 , wherein the mammal is human. 
     
     
         23 . (canceled) 
     
     
         24 . The method according to  claim 1 , wherein the polynucleotide encoding an active PDGF-D polypeptide is an expression vector expressing the PDGF-D polypeptide. 
     
     
         25 . The method according to  claim 24 , wherein the expression vector is delivered in a cell comprising the expression vector. 
     
     
         26 . The method according to  claim 25 , wherein the cell is a cell derived from the mammal in need thereof. 
     
     
         27 . The method according to  claim 24 , wherein the vector is a viral vector selected from the group consisting of a retrovirus vector, an adenovirus vector, an adeno-associated virus vector, a vaccinia virus vector, a herpes simplex virus vector, and a chimeric viral vector. 
     
     
         28 . The method according to  claim 1 , wherein the polynucleotide encoding an active PDGF-D polypeptide is a plasmid, and wherein the plasmid is topically administered in association with one or more additional therapies for wound-healing. 
     
     
         29 . The method according to  claim 28 , wherein the additional therapy for wound-healing is artificial skin or dressing for wounds.