Diagnosis and treatment for respiratory tract diseases
Inventors
Cohen, Noam A. • Lee, Robert J. • Reed, Danielle R.
Assignees
Monell Chemical Senses Center • University of Pennsylvania Penn • US Department of Veterans Affairs
Publication Number
US-10881698-B2
Publication Date
2021-01-05
Expiration Date
2033-01-25
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Abstract
The invention provides methods and compositions for the diagnosis, prognosis and treatment of respiratory tract diseases. Specifically, the invention provides diagnosis, prognosis and treatment of respiratory infections using bitter and sweet taste signal transduction pathways. In one aspect, the invention relates to a method for treating a respiratory infection by administering a composition to the respiratory tract of a subject in an amount capable of activating bitter taste signaling and/or inhibiting sweet taste signaling. The composition comprises at least a bitter receptor agonist and, optionally, a pharmaceutically acceptable carrier for delivering the composition to the respiratory tract. In another aspect, the invention relates to a composition for treatment of a respiratory infection. Such composition comprises at least a bitter receptor agonist and, optionally, a pharmaceutically acceptable carrier for delivering the composition to the respiratory tract.
Core Innovation
The invention provides methods and compositions for the diagnosis, prognosis and treatment of respiratory tract diseases, specifically respiratory infections, by using bitter and sweet taste signal transduction pathways. The invention includes methods for treating respiratory infections by administering a composition comprising at least a bitter receptor agonist to the respiratory tract of a subject, which activates bitter taste signaling and/or inhibits sweet taste signaling. This activation stimulates innate antimicrobial responses in the respiratory tract.
Respiratory infections such as chronic rhinosinusitis (CRS) affect a significant portion of the population and severely impact quality of life. Current treatments like antibiotics face challenges including resistance, and alternatives such as lytic enzymes and steroidal anti-inflammatory agents have limitations such as time consumption and side effects. The respiratory tract has endogenous defense mechanisms, including mucociliary clearance and secretion of antimicrobial peptides. Bitter taste receptors of the T2R family serve as sensors for bacterial products, activating defense responses upon detection. The invention leverages these bitter taste receptor pathways to enhance antimicrobial defense and proposes the use of bitter receptor agonists and sweet receptor antagonists to treat respiratory infections.
The invention also includes diagnostic and prognostic methods based on taste perception tests and detection of genetic polymorphisms in the T2R38 receptor, which is implicated in susceptibility to respiratory infections. Methods for determining the need for surgical intervention based on T2R38 genotype or phenotype tests are provided. The composition formulations cover various delivery means and carriers to effectively apply the bitter receptor agonists and/or sweet receptor antagonists to the respiratory tract.
Claims Coverage
The patent contains 2 independent claims focusing on methods for treating upper respiratory infections using specific bitter taste receptor agonists and compositions for stimulating innate antimicrobial responses.
Method for treating upper respiratory infection using bitter taste receptor agonists
Administering a bitter taste receptor agonist selected from quinine and salts thereof, denatonium, absinthin, salicin, phenylthiocarbamide (PTC), homoserine lactones, sodium thiocyanate (NaSCN), and 6-n-propylthio uracil (PROP) to the upper respiratory tract to activate bitter taste signaling pathways that stimulate nitric oxide (NO) production in sinonasal epithelial cells, thereby stimulating innate antimicrobial responses that treat the infection.
Method for treating upper respiratory infection associated diseases by administering T2R38 agonists
Administering a therapeutically effective amount of a T2R38 agonist selected from sodium thiocyanate (NaSCN), phenylthiocarbamide (PTC), butyryl-homoserine lactone (C4HSL), n-dodecanoyl-l-homoserine lactone (C12HSL), acetylthiourea (ATU), and 6-n-propylthio uracil (PROP) to stimulate NO production in sinonasal epithelial cells and induce innate antimicrobial responses.
The claims cover methods of treating upper respiratory infections and related diseases by administering specific bitter taste receptor agonists that activate bitter taste signaling and nitric oxide production to stimulate innate antimicrobial defense, including treatment targeted based on receptor genotypes and delivery forms suitable for the respiratory tract.
Stated Advantages
Enhanced activation of an immediate and vigorous innate antimicrobial response in the upper respiratory tract through manipulation of bitter and sweet taste signaling pathways.
Potential for treatment of upper respiratory infections that may overcome antibiotic resistance issues.
Non-steroidal treatment alternative that avoids side effects associated with steroidal anti-inflammatory agents.
Use of genetic and taste sensitivity testing to identify subjects at risk for respiratory infections and those who may benefit from specific treatments.
Formulation flexibility allowing various delivery modes and dosage forms suitable for effective application to the respiratory tract.
Documented Applications
Diagnosis, prognosis, and treatment of respiratory tract diseases, particularly respiratory infections such as chronic rhinosinusitis.
Use of bitter taste receptor agonists and sweet taste receptor antagonists to stimulate innate antimicrobial responses in the upper respiratory tract.
Genetic testing of T2R38 polymorphisms for assessing susceptibility to respiratory infections and determining need for surgical intervention.
Use of taste sensitivity tests for screening subjects susceptible to respiratory infections and identifying colonizing pathogens.
Treatment of respiratory infections in subjects with specific T2R38 genotypes by administering compounds such as quinine or extracts from Antidesma species.
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