Compositions and methods for the treatment of asthma and associated disorders
This disclosure provides methods for treating asthma or an associated disorder in a patient in need thereof, by administering to the patient an effective amount of an autophagy inducing agent, thereby treating the asthma or the associated disorder. Disorders that can be treated include, allergic asthma, chronic obstructive pulmonary disease, lung inflammation, respiratory tolerance and a lung infection or disorder.
1. A method for screening a compound or agent to treat asthma or a related disorder selected from the group of airway hyperreactivity (AHR), lung inflammation or respiratory tolerance, comprising administering to a transgenic mouse defective in autophagy protein 5 (Atg5), wherein the transgenic mouse expresses systemic or locally mutated Atg5 with reduced or abolished Atg5 expression, a candidate agent for an amount of time, and assaying for improved lung function by a method selected from the group of decreased airway resistance, decreased lung inflammation, increased autophagy in lung tissue, decreased cellular infiltration, decreased airway thickening, plethysmography, invasive plethysmography or T cell function in the mouse, wherein if the mouse has improved lung function, the compound or agent is a candidate for the treatment of asthma or a related disorder.
2. The method of claim 1 , wherein the asthma is allergic asthma.
3. The method of claim 1 , further comprising comparing the compound or agent that is a candidate for the treatment of asthma or a related disorder to an autophagy inducing agent selected from the group of carbomezepine, tamoxifen, minoxidil, erapumil, clonidine, and an autophagy inducing FLICE-like inhibitor protein (FLIP) peptide selected from the group of peptides identified by SEQ ID NO.: 1-8 or 14-28, or a peptide having at least 90% sequence identity to SEQ ID NO.: 1-8 or 14-28 and having the ability to induce autophagy.
4. The method of claim 3 , wherein the peptide has at least 95% sequence identity to the FLIP peptide and has the ability to induce autophagy.
5. The method of claim 3 , wherein the peptide having at least 90% sequence identity is a peptide coded by a polynucleotide that hybridizes to the coding or non-coding strand of a polynucleotide that encodes peptides identified by SEQ ID NO.: 1-8 or 14-28 under conditions of moderate or high stringency, wherein moderate stringency hybridization is typically performed at about 50° C. in about 6×SSC.
6. The method of claim 5 , wherein the conditions of high stringency are at about 60° C. in about 1×SSC.
7. The method of any one of claim 1 , 2 , or 3 , wherein the transgenic mouse defective in autophagy protein 5 (Atg5) function has a mutated or abolished Atg5 expression of greater than 90% in the lung and/or spleen.