Product and process for mucus viscosity normalization

Abstract

Disclosed are compositions and methods for decreasing the viscosity and/or cohesiveness of and/or increasing the liquefaction of excessively or abnormally viscous or cohesive mucus or sputum. The composition contains a protein or peptide containing a thioredoxin monocysteinic active site in a reduced state and optionally further contains a reducing system.

1 .- 54 . (canceled) 
     
     
         55 . A method of treating a human patient having cystic fibrosis comprising administering a pharmaceutical composition comprising a human thioredoxin homologue protein having a thioredoxin monocysteinic active site of W—C-G-P—S—K (SEQ ID NO: 27), wherein the C residue is in a reduced state. 
     
     
         56 . The method of  claim 55  wherein the pharmaceutical composition is formulated for oral administration or aerosol administration. 
     
     
         57 . The method of  claim 56 , wherein the pharmaceutical composition is formulated for aerosol administration. 
     
     
         58 . The method of  claim 55 , wherein the step of administering decreases viscoelasticity of mucus or sputum in the respiratory tract of the patient. 
     
     
         59 . The method of  claim 55 , wherein the step of administering increases the percentage of free thiols in mucus or sputum in the respiratory tract of the patient. 
     
     
         60 . The method of  claim 55 , wherein the step of administering increases forced expiratory volume (FEV) of the patient by at least about 2.5%. 
     
     
         61 . The method of  claim 55 , wherein the thioredoxin monocysteinic active site covalently binds to a cysteine residue in a mucus protein in the respiratory tract of the patient. 
     
     
         62 . A method of treating a human patient having cystic fibrosis comprising administering a pharmaceutical composition comprising a human thioredoxin homologue protein having a thioredoxin monocysteinic active site of W—C-G-P—S—K (SEQ ID NO: 27), wherein the C residue is in a reduced state and wherein the protein is administered to the respiratory tract of the patient. 
     
     
         63 . A pharmaceutical composition comprising a protein or peptide comprising a human thioredoxin homologue protein having a thioredoxin monocysteinic active site of W—C-G-P—S—K (SEQ ID NO: 27), wherein the C residue is in a reduced state, wherein the composition is formulated for aerosol administration to the lung. 
     
     
         64 . The pharmaceutical composition of  claim 63 , wherein the composition is in a nebulizer device. 
     
     
         65 . The pharmaceutical composition of  claim 63 , wherein the composition is in a vibrating mesh nebulizer device. 
     
     
         66 . A pharmaceutical composition comprising a protein or peptide comprising a monocysteinic thioredoxin active site in the reduced form. 
     
     
         67 . A composition comprising a human thioredoxin homologue protein having a thioredoxin monocysteinic active site of W—C-G-P—S—K (SEQ ID NO: 27), wherein the cysteine in the monocysteinic active site is covalently bound to a cysteine residue in a mucus protein. 
     
     
         68 . The composition of  claim 67 , wherein the mucus protein is a respiratory mucus protein. 
     
     
         69 . The composition of  claim 68 , wherein the mucus protein is a mucin. 
     
     
         70 . The composition of  claim 69 , wherein the mucin is a respiratory tract mucin. 
     
     
         71 . The composition of  claim 70 , wherein the respiratory tract mucin is selected from the group consisting of MUC5AC, MUC5B, and combinations thereof. 
     
     
         72 . The composition of  claim 69 , wherein the mucin is a digestive tract mucin. 
     
     
         73 . The composition of  claim 72 , wherein the mucin is MUC2. 
     
     
         74 . A method for preventing disulfide bond formation on an epithelial surface comprising forming a mixed-disulfide bond between a thiol group of a monocysteinic thioredoxin active site and a cysteine residue of an intramolecular or intermolecular protein disulfide located on a secreted or attached epithelial protein.