Methods and Compounds for Promoting Vessel Regression

Abstract

The present invention relates, at least in part, to methods and compositions for treating and diagnosing disorders associated with neovascularization, and methods for identifying targets and compositions used in treating and diagnosing such disorders.

1 . A method for identifying a candidate compound for the treatment of a disorder associated with neovascularization, the method comprising:
 providing a sample comprising a cell expressing activin receptor-like kinase-1 (ALK1);   contacting the sample with a test compound; and   monitoring expression of ALK1 in the cell,   
       wherein a test compound that increases the expression of ALK1 is a candidate compound for the treatment of neovascularization. 
     
     
         2 . A method for identifying a candidate therapeutic agent for the treatment of a disorder associated with neovascularization, the method comprising:
 providing an animal model of the disorder;   administering a candidate compound that increases the expression of activin receptor-like kinase-1 (ALK1) to the animal model; and   monitoring one or more parameters of the disorder in the animal,   
       wherein a candidate compound that improves a parameter of the disorder is a candidate therapeutic agent for the treatment of a disorder associated with neovascularization. 
     
     
         3 . A method of identifying a therapeutic agent for the treatment of a disorder associated with neovascularization, the method comprising:
 providing a subject having the disorder;   administering a candidate therapeutic agent that increases the expression of activin receptor-like kinase-1 (ALK1) to the subject; and   monitoring one or more parameters of the disorder in the subject,   
       wherein a candidate therapeutic agent that improves a parameter of the disorder is a therapeutic agent for the treatment of a disorder associated with neovascularization. 
     
     
         4 . The method of  claim 1 , wherein the sample comprises cells from a human fetus. 
     
     
         5 . The method of  claim 1 , wherein the sample comprises cells from a subject having a disorder associated with blood vessel regression. 
     
     
         6 . The method of  claim 5 , wherein the disorder is retinopathy of prematurity or retrolental fibroplasia. 
     
     
         7 . The method of  claim 1 , wherein the sample comprises cells from a subject in a stage of development that is associated with vessel regression. 
     
     
         8 . The method of  claim 7 , wherein the stage is the development of the hyaloid vascular system. 
     
     
         9 . The method of  claim 3 , wherein the subject is a human subject in a clinical trial. 
     
     
         10 . The method of  claims 1 , wherein the disorder associated with neovascularization is selected from the group consisting of extraocular and ocular neovascularization. 
     
     
         11 . The method of  claim 10 , wherein the ocular neovascularization is vitreous, retinal, choroidal, or corneal neovascularization. 
     
     
         12 . The method of  claim 1 , wherein the disorder associated with neovascularization is cancer. 
     
     
         13 . A method for treating a disorder associated with neovascularization in a subject, the method comprising administering a therapeutically effective amount of a therapeutic composition comprising an activin receptor-like kinase-1 (ALK1) polynucleotide or polypeptide, or an active fragment thereof. 
     
     
         14 . The method of  claim 13 , wherein the composition comprises an ALK1 polypeptide comprising amino acids 22-503 of SEQ ID NO:1, or an ALK1 nucleic acid molecule comprising nucleotides 346-1791 of SEQ ID NO:2. 
     
     
         15 . The method of  claim 13 , wherein the disorder is an ophthalmological disorder associated with neovascularization. 
     
     
         16 . The method of  claim 15 , wherein the ophthalmological disorder associated with neovascularization is selected from the group consisting of eye cancer, age-related macular degeneration, retinopathy of prematurity, corneal graft rejection, glaucoma, diabetic retinopathy, wounds, age-related macular degeneration, herpetic and infectious keratitis, ocular ischemia, neovascular glaucoma, corneal, uveal and iris neovascularization, orbital and eyelid tumors, Stevens Johnson Syndrome, ocular cicatricial pemphigoid, and ocular surface diseases. 
     
     
         17 . The method of  claim 15 , wherein the ophthalmological disorder is associated with corneal, retinal, choroidal, uveal, or iris neovascularization. 
     
     
         18 . The method of  claim 15 , wherein the administering is topical or parenteral administration into the eye. 
     
     
         19 . The method of  claim 17 , wherein the administering is by local injection into or near the cornea, retina, vitreous, uvea, orbit, eyelid, conjunctiva, or iris. 
     
     
         20 . The method of  claim 13 , wherein the disorder is cancer.