Methods of treatment of skin ulcers

Abstract

Methods for treating and/or preventing skin ulcers are provided featuring administration of pharmaceutical compositions comprising inhibitors of activity or expression of Lp-PLA 2 protein to patients subject to or at risk of developing skin ulcers.

What is claimed: 
     
         1 . A method of treating and/or preventing skin ulcers in a subject, comprising determining whether said subject has or is at risk of having a skin ulcer, and administering a pharmaceutical composition comprising an agent that inhibits the activity and/or the expression of the Lp-PLA 2  protein to the subject having a skin ulcer or at risk of developing a skin ulcer. 
     
     
         2 . The methods according to  claim 1 , wherein the subject is a mammal. 
     
     
         3 . The method according to  claim 2 , wherein the mammal is a human. 
     
     
         4 . The method according to  claim 1 , wherein risk factors are selected from a group consisting of having a previous episode of skin ulcer; having diabetes; being bedridden or wheelchair bound; and suffering from vasculitis. 
     
     
         5 . The method of  claim 1 , wherein the agent is a small molecule, nucleic acid, protein, antibody or antigen-binding fragment thereof. 
     
     
         6 . The method of  claim 5 , wherein the nucleic acid is an RNAi agent. 
     
     
         7 . The method of  claim 6 , wherein the RNAi agent is a siRNA, shRNA, miRNA, dsRNA or ribozyme or variants thereof. 
     
     
         8 . The method of  claim 5 , wherein the small molecule is 1-(N-(2-(diethylamino)ethyl)-N-(4-(4-trifluoromethylphenyl)benzyl)-aminocarbonylmethyl)-2-(4-fluorobenzyl)thio-5,6-trimethylenepyrimidin-4-one or SB480848 or a pharmaceutically acceptable salt or ester thereof. 
     
     
         9 . The method of  claim 5 , wherein the small molecule is N-(2-diethylaminoethyl)-2-[2-(2-(2,3-difluorophenyl)ethyl)-4-oxo-4,5,6,7-tetrahydro-cyclopentapyrimidin-1-yl]-N-(4′-trifluoromethyl-biphenyl-4-ylmethyl)acetamide or a pharmaceutically acceptable salt or ester thereof. 
     
     
         10 . The method of  claim 5 , wherein the small molecule is N-(1-(2-Methoxyethyl)piperidin-4-yl)-2-[2-(2,3-difluorobenzylthio)-4-oxo-4H-quinolin-1-yl]-N-(4′-trifluoromethylbiphenyl-4-ylmethyl)-acetamide; or a pharmaceutically acceptable salt or ester thereof. 
     
     
         11 . The method of  claim 5 , wherein the small molecule is methyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetyl}{[4′-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate or a pharmaceutically acceptable salt or ester thereof. 
     
     
         12 . The method of  claim 1 , further comprising administering to the subject an additional therapeutic agent. 
     
     
         13 . The method of  claim 12 , wherein said additional therapeutic agent is selected from the group consisting of anti-microbial therapy, anti-parasitic therapy, anti-obesity therapy, diabetes therapy, cardiovascular disease therapy, renal failure therapy, vasculitis therapy, venous insufficiency therapy, arterial insufficiency therapy, cancer therapy, immunosuppressant therapy, immunodeficiency therapy, steroid therapy, and burn therapy. 
     
     
         14 . The method of  claim 1 , further comprising administering to the subject the standard wound care management. 
     
     
         15 . The method Of  claim 1 , further comprising administering to the subject bioengineered skin substitutes.