Tmem100 peptides and variants thereof and their use in treating or preventing diseases or conditions

Abstract

The present invention features compositions of Tmem100 peptides and variants thereof, and their use in treating or preventing diseases or conditions.

1 . A method for treating or preventing a condition associated with TRPA1 function or for which reduced TRPA1 activity can reduce the severity, comprising administering an effective amount of a Tmem100 mutant polypeptide, or fragment thereof. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the TRPA1 function is an association with TRPV1. 
     
     
         5 . The method of  claim 4 , wherein the Tmem100 mutant polypeptide, or fragment thereof, enhances the association of TRPA1 with TRPV1. 
     
     
         6 . The method of  claim 1 , wherein said TRPA1 function is an inward TRPA1-mediated current, an outward TRPA1-mediated current, TRPA1-mediated ion flux or TRPA1-mediated neuronal hyperexcitability. 
     
     
         7 . The method of  claim 1 , wherein the Tmem100 mutant polypeptide comprises a polypeptide with one or more alterations in the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or fragments thereof. 
     
     
         8 . The method of  claim 1 , wherein the Tmem100 mutant polypeptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 17, or fragments thereof. 
     
     
         9 . The method of  claim 1 , wherein the Tmem100 mutant polypeptide, or fragment thereof, is provided to a cell and the cell is a sensory neuron. 
     
     
         10 . The method of  claim 9 , wherein the cell body of the sensory neuron resides in the dorsal root ganglia (DRG). 
     
     
         11 . The method of  claim 1 , used to prevent, treat, or alleviate symptoms of pain. 
     
     
         12 . The method of  claim 1 , used to prevent, treat, or alleviate symptoms of itch. 
     
     
         13 . The method of  claim 12 , wherein the pain is acute pain or chronic pain. 
     
     
         14 . The method of  claim 1 , wherein the Tmem100 mutant polypeptide, or fragment thereof, is administered in combination with one or more agents. 
     
     
         15 . The method of  claim 1 , wherein the Tmem100 mutant polypeptide, or fragment thereof, is administered in combination with one or more of a TRPV1 inhibitor, a TRPV3 inhibitor, a TRPV4 inhibitor, or a TRPM8 inhibitor. 
     
     
         16 . A pharmaceutical composition for treating or preventing a condition involving activation of TRPA1 or for which reduced TRPA1 activity can reduce the severity, comprising an effective amount of a Tmem100 mutant polypeptide, or fragment thereof. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the Tmem100 mutant polypeptide comprises a polypeptide with one or more alterations in the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or fragments thereof. 
     
     
         18 . The pharmaceutical composition of  claim 16 , wherein the Tmem100 mutant polypeptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, or fragments thereof. 
     
     
         19 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, or fragments thereof; or
 an isolated polypeptide encoded by a nucleic acid sequence comprising a nucleotide sequence selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, or fragments thereof; or   an isolated nucleic acid comprising a nucleotide sequence selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, or fragments thereof; or an isolated nucleic acid comprising a nucleotide sequence which encodes a polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, or fragments thereof.   
     
     
         20 - 25 . (canceled)