Adrenergic receptor overexpression in airway tissues for the treatment of airwayobstructive diseases

摘要

The present invention provides methods to protect a subject from a respiratory disorder involving an airway obstructive disease such as asthma or chronic obstructive pulmonary disease. Provided are methods to protect a subject from an airway obstructive disease using gene therapy. beta2-adrenergic receptors (beta2AR) act to relax airway smooth muscle and can serve to counteract hyperresponsiveness. Methods are provided for supplying beta2AR function to cells of the lung and airway, such as smooth muscle and epithelial cells, by beta2AR gene therapy. The beta2AR gene, a modified beta2AR gene, or a part of the gene may be introduced into the cell in a vector such that the gene remains extrachromosomal or may be integrated into the subjects chromosomal DNA for expression. These methods provide for administering to a subject in need of such treatment a therapeutically effective amount of a beta2AR gene, or pharmaceutically acceptable composition thereof, for overexpressing the beta2AR gene. Such methods of expressing the administered beta2AR gene in the lungs and airway provide for: (1) preventing or alleving bronchial hyperresponsiveness; (2) preventing or alleving of an airway obstructive disease, e.g., bronchial hyperreactivity, airway hyperresponsiveness, asthma or chronic obstructive pulmonary disorder ("COPD"); (3) reducing the airway resistance response to inhaled natural or synthetic bronchoconstrictors or allergens or to exercise; and (4) enhancing responsiveness (relaxation) of airway tissues to beta-agonists.