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Commentary: Ahead of the Curve |

The A’s Have It: Developing Apolipoprotein A-I Mimetic Peptides Into a Novel Treatment for Asthma

Xianglan Yao, MD, PhD; Elizabeth M. Gordon, PhD; Amisha V. Barochia, MBBS, MHS; Alan T. Remaley, MD, PhD; Stewart J. Levine, MD
Author and Funding Information

FUNDING/SUPPORT: This work was funded by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health (project number 1ZIAHL006054-06).

aLaboratory of Asthma and Lung Inflammation, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD

bLipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD

CORRESPONDENCE TO: Stewart J. Levine, MD, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg 10, Room 6D03, MSC 1590, Bethesda, MD 20892


Copyright 2016, . All Rights Reserved.


Chest. 2016;150(2):283-288. doi:10.1016/j.chest.2016.05.035
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New treatments are needed for patients with asthma who are refractory to standard therapies, such as individuals with a phenotype of “type 2-low” inflammation. This important clinical problem could potentially be addressed by the development of apolipoprotein A-I (apoA-I) mimetic peptides. ApoA-I interacts with its cellular receptor, the ATP-binding cassette subfamily A, member 1 (ABCA1), to facilitate cholesterol efflux out of cells to form nascent high-density lipoprotein particles. The ability of the apoA-I/ABCA1 pathway to promote cholesterol efflux from cells that mediate adaptive immunity, such as antigen-presenting cells, can attenuate their function. Data from experimental murine models have shown that the apoA-I/ABCA1 pathway can reduce neutrophilic airway inflammation, primarily by suppressing the production of granulocyte-colony stimulating factor. Furthermore, administration of apoA-I mimetic peptides to experimental murine models of allergic asthma has decreased both neutrophilic and eosinophilic airway inflammation, as well as airway hyperresponsiveness and mucous cell metaplasia. Higher serum levels of apoA-I have also been associated with less severe airflow obstruction in patients with asthma. Collectively, these results suggest that the apoA-I/ABCA1 pathway may have a protective effect in asthma, and support the concept of advancing inhaled apoA-I mimetic peptides to clinical trials that can assess their safety and effectiveness. Thus, we propose that the development of inhaled apoA-I mimetic peptides as a new treatment could represent a clinical advance for patients with severe asthma who are unresponsive to other therapies.

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