Methods and compositions relating to lung function
Inventors
BECKER, Elizabeth Jeanne • Steiling, Katrina • Spira, Avrum E. • Lenburg, Marc E.
Assignees
Publication Number
US-12329759-B2
Publication Date
2025-06-17
Expiration Date
2040-10-15
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Abstract
The technology described herein is directed to methods and compositions for prognosis and treatment of respiratory disease, e.g., COPD.
Core Innovation
The invention relates to methods and compositions for the prognosis and treatment of respiratory diseases, specifically chronic obstructive pulmonary disease (COPD). The central innovation is the identification of a bronchial airway gene expression profile that correlates with the rate of subsequent lung function decline, allowing diagnostic and therapeutic interventions to be targeted according to an individual's risk.
This approach solves the problem that, although COPD is characterized by progressive loss of lung function (as measured by FEV1), current risk factors like cigarette smoking or blood marker levels do not sufficiently predict which patients will experience rapid disease progression. By assessing the expression of specific genes—especially increased expression of certain genes (e.g., SURF4, S100A16, MIA3, TXNDC11) or decreased expression of others in bronchial or nasal epithelial samples—clinicians can identify patients at higher risk for rapid COPD progression, enabling earlier and more personalized treatment.
The invention further provides methods that tailor therapy based on this gene expression signature. Subjects with increased expression of particular genes are treated with one or more COPD therapies, such as inhaled long-acting antimuscarinics, long-acting β2 agonists, and inhaled corticosteroids. Those without the gene expression signature of risk receive alternatives, such as intensive smoking cessation therapy and short-acting β2 agonists. The gene expression profile can be determined using a sample obtained by bronchial brushing, biopsy, or nasal epithelium, and guides not only treatment, but also candidate drug screening and early detection of incipient disease.
Claims Coverage
The patent contains several inventive features as described in the independent claims and their main dependent variants.
Gene expression-guided treatment method for COPD
A method comprising: - Determining the level of expression of one or more genes from a first group (comprising SURF4, S100A16, MIA3, and TXNDC11) in a sample obtained from a subject in need of COPD treatment. - Administering to the subject: - One or more of an inhaled long-acting antimuscarinic, inhaled long-acting β2 agonist, or inhaled corticosteroid if the subject is determined to have an increased level of expression of one or more of the first group of genes relative to a reference (e.g., a never-smoker or age-matched never-smoker). - Alternatively, administering intensive smoking cessation therapy and/or an inhaled short-acting β2 agonist if the subject is not determined to have such an increased level.
Gene panel extension for risk assessment
A method further comprising determining the level of expression of additional genes (such as GALE, SEC61A1, KDELR2, ADAM9, and TMED3) in the sample, for refinement of risk stratification and treatment guidance.
Assessment using specific sample types
The sample for expression analysis can be obtained via bronchial brushing, bronchial biopsy, bronchial epithelium, airway epithelium, nasal brushing, or nasal epithelium, and the method includes such sample types explicitly.
Target population specification
The method is further characterized as applicable to subjects who are current or former tobacco smokers, humans (optionally at least 49 or 58 years old), or subjects with a GOLD grade of 2 or lower.
Therapy selection according to refined reference levels
Administration of treatment is defined in relation to reference levels, such as the value in a patient who has never smoked, an age-matched never-smoker, a control sample/pool, or the average level in a population.
Treatment customization based on multi-gene expression signature
A method involving measurement of the gene expression profile of a defined second group of genes (such as KIF13A, TBC1D22B, CCDC69, PRKCE, etc.), wherein a decreased level of these is combined with an increased level of the first group of genes to further stratify risk and treatment.
The claims cover a personalized medicine approach to COPD and related respiratory disease treatment, wherein gene expression profiling from airway or nasal samples determines the specific therapy administered, thus tailoring intervention based on molecular prognosis.
Stated Advantages
The invention enables identification of individuals with incipient COPD before substantial lung function loss, permitting early and effective intervention.
It permits patient stratification and targeting of therapy to those most likely to benefit based on risk of rapid lung function decline.
The gene expression signature serves as a prognostic marker for rate of FEV1 decline, addressing heterogeneity not explained by traditional risk factors.
The approach can facilitate clinical trials by identifying individuals most likely to experience greater decline in FEV1.
The method provides additional indications for discovering therapeutic targets to slow COPD progression.
Documented Applications
Prognosis and treatment of chronic obstructive pulmonary disease (COPD) by tailoring therapy based on airway or nasal gene expression profiles.
Identifying individuals at risk for more rapid decline in lung function, especially among current or former smokers, or those exposed to environmental hazards.
Screening tool to identify promising new drug candidates by targeting normalization of the gene expression signature.
Monitoring of therapy efficacy and stratification of patients for clinical trials based on molecular markers.
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