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Treatment and inhibition of inflammatory lung diseases in patients having risk alleles in genes encoding il33 and il1rl1

An allele and risk technology, applied in the field of alleles, can solve problems such as poor results

Pending Publication Date: 2019-11-08
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Likewise, other treatments such as IL-5 therapy do not work as well for the eosinophilic subtype of asthma and COPD

Method used

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  • Treatment and inhibition of inflammatory lung diseases in patients having risk alleles in genes encoding il33 and il1rl1
  • Treatment and inhibition of inflammatory lung diseases in patients having risk alleles in genes encoding il33 and il1rl1
  • Treatment and inhibition of inflammatory lung diseases in patients having risk alleles in genes encoding il33 and il1rl1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Anti-IL33 antibody, anti-IL-4R antibody and combination of both in chronic house dust mite-induced fibrosis and severe lung inflammation model

[0104] Chronic inflammatory airway disease is the result of recurrent episodes of airway inflammation primarily due to repeated exposure to allergens or other pathogens. In humans, such chronic injury induces a host of pathologies, including immune cell infiltration of the lungs, increased cytokine production, mucus production, and collagen deposition. This increase in inflammatory cytokines and immune cell infiltrates is accompanied by intense airway remodeling, leading to airway narrowing, hyperresponsiveness to inhaled triggers such as allergens or pathogens, airway obstruction, and loss of lung function.

[0105] To determine the effect of anti-IL33 inhibition in a relevant in vivo model, chronic house dust mite extract (HDM) induction was performed in mice homozygous for expression of human IL33 but not mouse IL33 (IL33 Hu...

Embodiment 2

[0159] Genetic variants in IL33 and its receptor are associated with eosinophilic asthma and COPD

[0160] In this example, the relationship between previously identified asthma risk variants at IL33 and IL1RL1 and the risk of asthma, COPD, and ACOS was examined in the largest combined set of such cases that has been aggregated, where genetic data and electronic health records related. The significance of these variants for the eosinophilic subtypes of asthma, COPD and ACOS and for related upper respiratory diseases such as nasal polyps was examined. Additionally, the association between predicted loss-of-function variants (pLOF) in IL1RL1 and IL33 and these diseases was evaluated.

[0161] Human Genetics Research Supervision. The human genetics study was part of the DiscovEHR research at the Regeneron Genetics Center (RGC) and Geisinger Health System (GHS).

[0162] DiscovEHR participants and disease definitions. At the time of this study, the DiscovEHR study included the...

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Abstract

IL33 antagonists alone or in combination with IL-4R antagonists can be used to treat or inhibit eosinophilic asthma, eosinophilic COPD, eosinophilic ACOS, and nasal polyps in a subject having one or more risk alleles in the intronic IL1RL1 variant rs1420101, in the IL33 variant rs1342326, in both, or in variants in linkage disequilibrium thereof.

Description

technical field [0001] The present disclosure relates generally to the field of precision medicine. More specifically, the present disclosure relates to the detection of risk alleles in the genes encoding IL33 and IL1RL1 that can be used to stratify inflammatory lung disease patients as those at risk of developing these conditions and their eosinophilicity High risk for one or more of the subtypes. Background technique [0002] Various publications are cited throughout the specification, including patents, published applications, accession numbers, technical literature, and scholarly literature. Each of these cited publications is hereby incorporated by reference in its entirety for all purposes. [0003] Asthma and chronic obstructive pulmonary disease (COPD) are very prevalent obstructive lung diseases with large unmet clinical needs and significant diagnostic overlap, and the intersection of these conditions (termed asthma-COPD overlap syndrome (ACOS) ) are becoming mo...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883
CPCC12Q1/6883C12Q2600/106C12Q2600/112C12Q2600/156A61P11/00A61P11/06C07K16/244C07K16/2866C07K2317/76A61K2039/507
Inventor 香农·布鲁斯沙恩·麦卡锡阿里斯·巴拉斯弗雷德里克·杜威奥姆里·戈特斯曼
Owner REGENERON PHARM INC
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