Cortistatin: neuropeptides, compositions and methods

Abstract

The present invention relates generally to nucleic acids encoding a novel neuropeptide designated cortistatin. The cortistatin nucleic acids, proteins and polypeptides thereof along with anti-cortistatin antibodies are useful in both screening methods, diagnostic methods and therapeutic methods related to modulation of sleep and disorders thereof.

1 - 23 . (canceled)  
     
     
         24 . A method for inducing slow wave sleep in a human subject comprising administering a pharmaceutical composition of an isolated and purified cortistatin polypeptide to the human subject, wherein the cortistatin polypeptide comprises a sequence selected from the group consisting of SEQ ID NO: 26, positions 44 to 74 of SEQ ID NO: 26, positions 77 to 105 of SEQ ID NO: 26, and positions 89 to 105 of SEQ ID NO: 26.  
     
     
         25 . The method of  claim 24 , wherein the sequence of the polypeptide ranges from positions 89 to 105 of SEQ ID NO: 26.  
     
     
         26 . The method of  claim 24 , wherein the pharmaceutical composition is administered in a physiologically tolerable amount that is sufficient to achieve a plasma concentration of from about 0.1 μM to about 100 μM.  
     
     
         27 . The method of  claim 26 , wherein the pharmaceutical composition is administered in a physiologically tolerable amount that is sufficient to achieve a plasma concentration of from about 0.5 μM to about 10 μM.  
     
     
         28 . The method of  claim 24 , wherein the pharmaceutical composition is administered intravenously.  
     
     
         29 . A method for inducing slow wave sleep in a human subject comprising administering a pharmaceutical composition of an isolated and purified nucleic acid which codes for a cortistatin polypeptide to the human subject, wherein the cortistatin polypeptide comprises a sequence selected from the group consisting of SEQ ID NO: 26, positions 44 to 74 of SEQ ID NO: 26, positions 77 to 105 of SEQ ID NO: 26, and positions 89 to 105 of SEQ ID NO: 26.  
     
     
         30 . The method of  claim 29 , wherein the sequence of the polypeptide ranges from positions 89 to 105 of SEQ ID NO: 26.  
     
     
         31 . The method of  claim 29 , wherein the pharmaceutical composition is administered intravenously.  
     
     
         32 . A method for identifying a ligand that binds to a cortistatin receptor comprising: 
 contacting a mammalian cell having a cortistatin receptor with a candidate ligand under conditions permitting binding of a known cortistatin receptor ligand to the cortistatin receptor; and    detecting the presence of the candidate ligand bound to the receptor.    
     
     
         33 . The method of  claim 32 , wherein the candidate ligand is labeled.