Treatment of neovascularization disorders with squalamine

Abstract

Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.

1 - 3 . (canceled)  
   
   
       4 . A method of treating retinopathy in a mammal, comprising administering to the mammal a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the retinopathy.  
   
   
       5 . The method of  claim 4 , wherein the effective amount is about 0.1 to about 10 mg/kg body weight.  
   
   
       6 . The method of  claim 4 , wherein the mammal is a human.  
   
   
       7 . The method of  claim 4 , wherein the composition is administered intravenously.  
   
   
       8 . The method of  claim 4 , wherein the retinopathy is diabetic retinopathy.  
   
   
       9 . The method of  claim 4 , wherein the retinopathy is retinopathy of prematurity.  
   
   
       10 . A method of treating retinopathy in a human, comprising administering systemically to the human in need of treatment, a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the retinopathy.  
   
   
       11 . The method of  claim 10 , wherein the systemic administration is selected from the group consisting of intravenous, subcutaneous and intramuscular injection.  
   
   
       12 . The method of  claim 10 , wherein the retinopathy is diabetic retinopathy.  
   
   
       13 . The method of  claim 10 , wherein the retinopathy is retinopathy of prematurity.  
   
   
       14 . The method of  claim 10 , wherein the method consists essentially of administering to the human in need treatment, a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the retinopathy.  
   
   
       15 . The method of  claim 14 , wherein the retinopathy is diabetic retinopathy.  
   
   
       16 . The method of  claim 10 , wherein the method consists of administering to the human in need of treatment, a composition comprising an amount of squalamine or a pharmaceutically acceptable salt thereof effective to treat the retinopathy.  
   
   
       17 . The method of  claim 16 , wherein the retinopathy is diabetic retinopathy.  
   
   
       18 . The method of  claim 4  or  claim 10 , wherein the composition consists essentially of squalamine.  
   
   
       19 . The method of  claim 4  or  claim 10 , wherein the composition consists of squalamine.  
   
   
       20 . The method of  claim 4  or  claim 10 , wherein the composition further comprises one or more pharmaceutically acceptable excipients.  
   
   
       21 . The method of  claim 4  or  claim 10 , wherein the composition is used in combination with at least one other therapy for treating retinopathy.