Compositions and Methods of Treating or Preventing Fibrotic Lung Diseases

Abstract

The invention includes a method of preventing or treating a fibrotic lung disease in a subject, comprising administering to the subject a thyroid receptor β-agonist. The invention further comprises compositions and kits comprising compositions useful within the invention.

1 . A method of treating or ameliorating a fibrotic lung disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of at least one thyroid receptor (TR) β-agonist. 
     
     
         2 . The method of  claim 1 , wherein the at least one TR β-agonist comprises at least one selected from the group consisting of GC-1 (2-(4-(4-hydroxy-3-isopropylbenzyl)-3,5-dimethylphenoxy) acetic acid), KB-2115 (3-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)anilino]-3-oxopropanoic acid), KB-141 (({3,5-dichloro-4-[4-hydroxy-3-(propan-2-yl)phenoxy]phenyl} acetic acid), MB07811 ((4S)-4-(3-chlorophenyl)-2-[(3,5-dimethyl-4-(4-hydroxy-3-isopropylbenzyl)phenoxy)methyl]-2-oxido-[1,3,2]-dioxaphosphonane), and MB07344 (3,5-dimethyl-4-(4′-hydroxy-3′-isopropylbenzyl)phenoxy methylphosphonic acid), or any salt, ester, or solvate thereof. 
     
     
         3 . The method of  claim 1 , wherein the at least one TR β-agonist comprises GC-1, or any salt, ester, or solvate thereof. 
     
     
         4 . The method of  claim 1 , wherein the fibrotic lung disease comprises idiopathic pulmonary fibrosis. 
     
     
         5 . The method of  claim 1 , wherein the at least one TR β-agonist is the only pharmaceutically active agent administered to the subject. 
     
     
         6 . The method of  claim 1 , wherein the at least one TR β-agonist is the only pharmaceutically active agent administered to the subject in sufficient amount to treat or ameliorate the fibrotic lung disease. 
     
     
         7 . The method of  claim 1 , wherein the subject is further administered at least one additional agent that treats or reduces the symptoms of the fibrotic lung disease. 
     
     
         8 . The method of  claim 7 , wherein the at least one additional agent comprises at least one selected from the group consisting of pirfenidone and nintadanib. 
     
     
         9 . The method of  claim 1 , wherein the subject is administered a daily dose of at least one TR β-agonist ranging from about 10 to about 40 μg/kg. 
     
     
         10 . The method of  claim 1 , wherein administration of the at least one TR β-agonist does not cause significant or undesirable cardiac stimulation, weight loss, or blood lipid decrease in the subject. 
     
     
         11 . The method of  claim 1 , wherein the at least one TR β-agonist is administered to the subject at a frequency selected from the group consisting of about three times a day, about twice a day, about once a day, about every other day, about every third day, about every fourth day, about every fifth day, about every sixth day, and about once a week. 
     
     
         12 . The method of  claim 1 , wherein the at least one TR β-agonist is administered to the subject through a route selected from the group consisting of oral, parenteral, nasal, intravenous, subcutaneous, enteral, pulmonary, aerosol, ophthalmic, inhalational, intratracheal, intrabronchial, and topical. 
     
     
         13 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         14 . The method of  claim 13 , wherein the mammal is a human. 
     
     
         15 . A kit comprising at least one TR β-agonist, an applicator, and an instructional material for use thereof, wherein the instructional material comprises instructions for treating or ameliorating a fibrotic lung disease in a subject comprising administering the at least one TR β-agonist to the subject. 
     
     
         16 . The kit of  claim 15 , further comprising at least one additional agent that treats or reduces the symptoms of the fibrotic lung disease. 
     
     
         17 . The kit of  claim 16 , wherein the at least one additional agent comprises pirfenidone or nintadanib.