Asthma associated factors as targets for treating atopic allergies including asthma and related disorders

Abstract

A new gene in the calcium-activated chloride channel family has been discovered that is induced by IL-9, thereby providing a therapeutic target in IL-9 mediated development of atopic allergy, asthma-related disorders and cystic fibrosis. A method for the identification and use of small molecule inhibitors of this gene and its products to treat these disorders has also been discovered. The invention also includes a method for diagnosing susceptibility to, and assessing treatment of atopic allergy, asthma-related disorders by measuring the level of gene expression in biologic samples using antibody specific for this protein.

1 . A purified and isolated nucleic acid molecule selected from the group consisting of a nucleic acid molecule having a nucleotide sequence encoding human ICACC-1 (SEQ ID NO: 6), a nucleic acid molecule which hybridizes to a nucleic acid molecule having SEQ ID NO: 1, a nucleic acid molecule encoding murine ICACC-1 (SEQ ID NO: 2), a nucleic acid molecule encoding human ICACC-2 (SEQ ID NO: 4) and a nucleic acid molecule comprising functionally effective fragments thereof. 
     
     
         2 . A purified and isolated DNA molecule of  claim 1  having a nucleotide sequence encoding murine ICACC-1 (SEQ ID NO: 2) or functionally effective fragments thereof. 
     
     
         3 . A purified and isolated DNA molecule of  claim 1  having a nucleotide sequence encoding human ICACC-2 (SEQ ID NO: 4) or functionally effective fragments thereof. 
     
     
         4 . The purified and isolated nucleic acid molecule of  claim 1  wherein said molecule is genomic DNA. 
     
     
         5 - 10 . (canceled) 
     
     
         11 . A purified and isolated protein molecule selected from the group consisting of a purified and isolated protein having an amino acid sequence comprising human ICACC-1 (SEQ ID NO: 6) or functionally effective fragments thereof, a purified and isolated protein molecule having an amino acid sequence comprising murine ICACC-1 (SEQ ID NO: 2) or functionally effective fragments thereof and a purified and isolated protein molecule having an amino acid sequence comprising human ICACC-1 (SEQ ID NO: 4) or functionally effective fragments thereof. 
     
     
         12 . A purified and isolated protein molecule of  claim 11  having an amino acid sequence comprising murine ICACC-1 (SEQ ID NO: 2) or functionally effective fragments thereof. 
     
     
         13 . A purified and isolated protein molecule of  claim 11  having an amino acid sequence comprising human ICACC-1 (SEQ ID NO: 4) or functionally effective fragments thereof. 
     
     
         14 . A method of alleviating asthma by administering to patients in need of such treatment an effective amount of a compound or an antibody that blocks the function of an ICACC to down-regulate the function of human ICACC-1. 
     
     
         15 . A method according to  claim 14  wherein the compound is a chloride channel inhibitor. 
     
     
         16 . A method according to  claim 14  wherein the compound is an aminosterol. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 14  wherein the antibody is produced from peptides that encompass the functional domains of ICACC-1. 
     
     
         19 . A method according to  claim 14  wherein the antibody is produced from peptides taken from the group of SEQ ID NO: 11-15. 
     
     
         20 . The method of  claim 14  wherein the antibody is monoclonal. 
     
     
         21 - 29 . (canceled) 
     
     
         30 . Antisense DNA comprising the antisense sequence of a nucleic acid molecule of  claim 1  or active fragments thereof. 
     
     
         31 . A method according to  claim 14  wherein the compound is the antisense DNA of  claim 30 . 
     
     
         32 - 36 . (canceled)