METHODS FOR TREATING LUNG DISEASE
The methods and assays described herein relate to the diagnosis, prognosis, and treatment of subjects with emphysema, COPD, and/or cigarette-induced lung damage. In some embodiments, the methods and assays relate to subjects with a decreased level of NLRX1 expression. In some embodiments, the methods and assays relate to the administration of an agonist of NLRX1 and/or an inhibitor of MAVS.
1 . A method of treating COPD, cigarette smoke-induced lung damage, or emphysema in a subject in need thereof, the method comprising administering an inhibitor of MAVS.
2 . The method of claim 1 , wherein the cigarette smoke-induced lung damage is selected from the group consisting of:
inflammation; alveolar destruction; protease induction; structural cell apoptosis; and inflammasome activation.
3 . The method of claim 1 , wherein the emphysema is cigarette smoke induced emphysema.
4 . The method of claim 1 , wherein the inhibitor of MAVS is an agonist of NLRX1.
5 . The method of claim 1 , wherein the inhibitor of MAVS is a modulator of NLRX1-dependent pathways.
6 . The method of claim 4 , wherein the agonist of NLRX1 is a nucleic acid encoding NLRX1 or an NLRX1 polypeptide.
7 . The method of claim 1 , wherein the subject is a subject determined to have a decreased level of NLRX1 expression.
8 . A method of treatment for COPD, emphysema, and/or cigarette-induced lung damage comprising;
measuring the level of NLRX1 in a test sample obtained from a subject;
treating the subject when the level of NLRX1 is decreased relative to a reference level.
9 . The method of claim 8 , wherein the treatment comprises a treatment selected from the group consisting of:
administration of a bronchodilator; administration of an inhaled steroid; administration of oxygen therapy; bullectomy; lung volume reduction surgery; smoking cessation; lung transplant; administration of an inhibitor of MAVS; administration of an agonist of NLRX1; administration of a nucleic acid encoding NLRX1; and administration of a NLRX1 polypeptide.
10 . The method of claim 8 , wherein the level of NLRX1 is determined by measuring the level of a nucleic acid.
11 . The method of claim 10 , wherein the level of NLRX1 is determined by measuring the level of NLRX1 RNA transcript.
12 . The method of claim 10 , wherein the level of the nucleic acid is determined using a method selected from the group consisting of:
RT-PCR; quantitative RT-PCR; Northern blot; microarray based expression analysis; next-generation sequencing; and RNA in situ hybridization.
13 . The method of claim 8 , wherein the level of NLRX1 is determined by measuring the level of NLRX1 polypeptide.
14 . The method of claim 13 , wherein the level of the polypeptide is determined using a method selected from the group consisting of:
Western blot; immunoprecipitation; enzyme-linked immunosorbent assay (ELISA); radioimmunological assay (RIA); sandwich assay; fluorescence in situ hybridization (FISH); immunohistological staining; radioimmunometric assay; immunofluoresence assay; mass spectroscopy; FACS; and immunoelectrophoresis assay.
15 . The method of claim 13 , wherein the polypeptide level is measured using immunochemistry.
16 . The method of claim 15 , wherein the antibody reagent is detectably labeled or generates a detectable signal.
17 . The method of claim 8 , wherein the expression level of NLRX1 is normalized relative to the expression level of one or more reference genes or reference proteins.
18 . The method of claim 17 , wherein the reference level of NLRX1 is the expression level of NLRX1 in a prior sample obtained from the subject.
19 . The method of claim 8 , wherein the subject is a subject with a history of smoking.
20 . The method of claim 8 , wherein the sample is selected from the group consisting of:
a lung biopsy; bronchoalveolar lavage (BAL); sputum; induced sputum; blood; plasma; and serum.