Treatment for asthma or allergies

Abstract

Several genes are upregulated in the lung of asthma or allergy sufferers. Many of the genes up-regulated in asthma are involved in arginine metabolism in the lung. Moreover, a set of 291 signature genes was found that can be used to indicate a patient's predilection for developing asthma or the patient's degree of suffering. Also, a set of 59 signature genes were found that indicate a patient's predilection for developing allergies. Many of the up-regulated genes relating to asthma were from the arginine metabolic pathway. Other genes, such as ADAM8, SPRR2A and SPRR2B were also strongly up-regulated in asthma. Treatment of asthma may be accomplished by administering compositions which decrease the levels of Arginase I, Arginase II, CAT2, or other arginase pathway members in the lung. Additionally, detection of altered levels of these proteins or the mRNA encoding them may be useful to diagnose the presence of asthma in a patient.

What is claimed is:  
     
         1 . A method of treating asthma or allergies in a patient, comprising: 
 identifying an individual in need of treatment for asthma or allergies; and    administering a molecule that is capable of decreasing the production of a protein involved in arginine metabolism.    
     
     
         2 . The method of  claim 1 , wherein protein is selected from the group consisting of: CAT2, arginase I and arginase II.  
     
     
         3 . The method of  claim 1 , wherein said molecule decreases the production of said protein by inhibiting a gene encoding said protein.  
     
     
         4 . The method of  claim 1 , further comprising administration of a compound capable of decreasing or inhibiting pulmonary levels of Interleukin-4 or Interleukin-13.  
     
     
         5 . A method of detecting the presence of asthma or allergies in a patient comprising: 
 measuring the levels a product produced from at least one gene involved in arginine metabolism from said patient;    measuring genetic variabilities (in expression or gene sequence) from a product produced from at least one gene involved in arginine metabolism; and    comparing said measurement to measurements obtained from control individuals, wherein a patient exhibiting higher levels of said at least one gene as compared to the control individuals is determined to have asthma or allergies.    
     
     
         6 . The method of  claim 5 , wherein said at least one gene is selected from the group consisting of: CAT2, arginase I, and arginase II.  
     
     
         7 . The method of  claim 5 , wherein said product is an mRNA.  
     
     
         8 . The method of  claim 5 , wherein said product is a protein.  
     
     
         9 . A therapeutic composition for the treatment of asthma or allergies, comprising an arginase inhibitor in a pharmaceutically acceptable carrier.  
     
     
         10 . A therapeutic composition for the treatment of asthma or allergies, comprising an inhibitor of CAT2 activity in a pharmaceutically acceptable carrier.  
     
     
         11 . A method of identifying individuals at risk for asthma or allergies, comprising: 
 identifying an individual who does not yet exhibit symptoms of asthma or allergy,    measuring the levels of a product produced from a gene in the arginase pathway; and    comparing said levels of product to measurements obtained from control individuals, wherein a patient exhibiting elevated levels of said product is determined to be at risk for asthma or allergies.    
     
     
         12 . The method of  claim 11 , wherein said gene in the arginase pathway is selected from the group consisting of: Arginase I, Arginase II, and CAT2.  
     
     
         13 . The method of  claim 11 , wherein said product in mRNA.  
     
     
         14 . The method of  claim 11 , wherein said product is a protein.  
     
     
         15 . A method of treating asthma or allergies in a patient, comprising: 
 identifying an individual in need of treatment for asthma or allergies; and    administering a molecule that is capable of decreasing activity of ADAM8 protein in said patient.    
     
     
         16 . The method of  claim 15 , wherein said molecule changes the structure of ADAM8.  
     
     
         17 . The method of  claim 16 , wherein the molecule converts ADAM8 from a transmembrane to a soluble form.  
     
     
         18 . The method of  claim 15 , wherein said molecule decreases activity of ADAM8 by inhibiting a gene encoding the ADAM8 protein.  
     
     
         19 . The method of  claim 15 , further comprising administration of a compound capable of decreasing or inhibiting pulmonary levels of Interleukin-4 or Interleukin-13.  
     
     
         20 . A method of treating asthma or allergies in a patient, comprising: 
 identifying an individual in need of treatment for asthma or allergies; and    administering a molecule that is capable of decreasing activity of SPRR2A, SPRR2B or related SPRR family member proteins in said patient.    
     
     
         21 . The method of  claim 20 , wherein said molecule decreases activity of SPRR2A protein by inhibiting a gene encoding the SPRR2A protein.  
     
     
         22 . The method of  claim 20 , wherein said molecule decreases activity of SPRR2B protein by inhibiting a gene encoding the SPRR2B protein.  
     
     
         23 . A method of determining a patient's risk for developing asthma, comprising: 
 providing a biological sample from the patient; and    determining the expression level in the biological sample of a subset of the genes shown in Table 1, wherein an increased level of expression of said subset of the genes in comparison to a control biological sample is indicative that the patient has an increased risk for developing asthma.    
     
     
         24 . The method of  claim 23 , wherein said subset comprises at least 1 percent of the genes shown in Table 1.  
     
     
         25 . The method of  claim 23 , wherein said subset comprises at least 30 percent of the genes shown in Table 1.  
     
     
         26 . The method of  claim 23 , wherein said subset comprises at least 50 percent of the genes shown in Table 1.  
     
     
         27 . The method of  claim 23 , wherein said subset comprises at least 80 percent of the genes shown in Table 1.  
     
     
         28 . A method of determining a patient's risk for developing allergies, comprising: 
 providing a biological sample from the patient; and    determining the expression level in the biological sample of a subset of the genes shown in Table 2, wherein an increased level of expression of said subset of the genes in comparison to a control biological sample is indicative that the patient has an increased risk for developing allergies.    
     
     
         29 . The method of  claim 28 , wherein said subset comprises at least 1 percent of the genes shown in Table 2.  
     
     
         30 . The method of  claim 28 , wherein said subset comprises at least 30 percent of the genes shown in Table 2.  
     
     
         31 . The method of  claim 28 , wherein said subset comprises at least 50 percent of the genes shown in Table 2.  
     
     
         32 . The method of  claim 28 , wherein said subset comprises at least 80 percent of the genes shown in Table 2.  
     
     
         33 . A method of discovering a compound that is effective for treating asthma or allergies, comprising: 
 providing a candidate compound;    determining whether said compound inhibits aginine metabolism, wherein inhibition of arginine metabolism is indicative that said compound is effective for treating asthma or allergies.    
     
     
         34 . The method of  claim 33 , wherein said compound is an inhibitor of Arginase I activity.  
     
     
         35 . The method of  claim 33 , wherein said compound is an inhibitor of Arginase II activity.  
     
     
         36 . The method of  claim 33 , wherein said compound is an inhibitor of CAT2 activity.