Biologic therapies for asthma

Gruenberg, David A.; Busse, William W.

doi:10.1097/mcp.0b013e3283328398

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…Steroid agents used to treat asthma have side effects when administered in high concentrations over long periods of time, and compliance with inhalers remains an important therapeutic issue. While biologic therapies show potential (42), they too have side effects and are costly. Data presented in this study indicate that treatment with a new type of immunomodulator, the GABA A R agonist HNK, modulated inflammation associated with asthma at a dose that was well tolerated with multiple injections over the course of several weeks in a well-studied model of allergic airway inflammation, and which falls within pharmacokinetic range (43).…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of the Neurotransmitter Agonist Honokiol in a Mouse Model of Allergic Asthma

Munroe

Businga

Kline

et al. 2010

The Journal of Immunology

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Chronic airway inflammation is a hallmark of asthma, an immune-based disease with great societal impact. Honokiol (HNK), a phenolic neurotransmitter receptor (γ-aminobutyric acid type A) agonist purified from magnolia, has anti-inflammatory properties, including stabilization of inflammation in experimentally induced arthritis. The present study tested the prediction that HNK could inhibit the chronic inflammatory component of allergic asthma. C57BL/6 mice sensitized to and challenged with OVA had increased airway hyperresponsiveness to methacholine challenge and eosinophilia compared with naive controls. HNK-treated mice showed a reduction in airway hyperresponsiveness as well as a significant decrease in lung eosinophilia. Histopathology studies revealed a marked drop in lung inflammation, goblet cell hyperplasia, and collagen deposition with HNK treatment. Ag recall responses from HNK-treated mice showed decreased proinflammatory cytokines in response to OVA, including TNF-α–, IL-6–, Th1-, and Th17-type cytokines, despite an increase in Th2-type cytokines. Regulatory cytokines IL-10 and TGF-β were also increased. Assessment of lung homogenates revealed a similar pattern of cytokines, with a noted increase in the number of FoxP3+ cells in the lung. HNK was able to alter B and T lymphocyte cytokine secretion in a γ-aminobutyric acid type A-dependent manner. These results indicate that symptoms and pathology of asthma can be alleviated even in the presence of increased Th2 cytokines and that neurotransmitter agonists such as HNK have promise as a novel class of anti-inflammatory agents in the treatment of chronic asthma.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of the Neurotransmitter Agonist Honokiol in a Mouse Model of Allergic Asthma

Munroe

Businga

Kline

et al. 2010

The Journal of Immunology

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“…For example, a clinical trial in which mepolizumab was given to patients with asthma for 6 months showed reduced exacerbation frequency and steroid requirements [104,105]. Gruenberg and Busse's study [106] suggested that patients who are being treated with steroid therapy and continue to have persistent sputum eosinophilia may benefit from an agent that can specifically target and reduce eosinophils. Clinical trials with other anti IL-5 antibodies, including reslizumab and enralizumab, are currently in progress.…”

Section: Recent Treatment Strategies For Airway Remodelingmentioning

confidence: 99%

Recent Advances in Mechanisms and Treatments of Airway Remodeling in Asthma: A Message from the Bench Side to the Clinic

Cho

2011

Korean J Intern Med

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Airway remodeling in asthma is a result of persistent inflammation and epithelial damage in response to repetitive injury. Recent studies have identified several important mediators associated with airway remodeling in asthma, including transforming growth factor-β, interleukin (IL)-5, basic fibroblast growth factor, vascular endothelial growth factor, LIGHT, tumor necrosis factor (TNF)-α, thymic stromal lymphopoietin, IL-33, and IL-25. In addition, the epithelium mesenchymal transformation (EMT) induced by environmental factors may play an important role in initiating this process. Diagnostic methods using sputum and blood biomarkers as well as radiological interventions have been developed to distinguish between asthma sub-phenotypes. Human clinical trials have been conducted to evaluate biological therapies that target individual inflammatory cells or mediators including anti IgE, anti IL-5, and anti TNF-α. Furthermore, new drugs such as c-kit/platelet-derived growth factor receptor kinase inhibitors, endothelin-1 receptor antagonists, calcium channel inhibitors, and HMG-CoA reductase inhibitors have been developed to treat asthma-related symptoms. In addition to targeting specific inflammatory cells or mediators, preventing the initiation of EMT may be important for targeted treatment. Interestingly, bronchial thermoplasty reduces smooth muscle mass in patients with severe asthma and improves asthma-specific quality of life, particularly by reducing severe exacerbation and healthcare use. A wide range of different therapeutic approaches has been developed to address the immunological processes of asthma and to treat this complex chronic illness. An important future direction may be to investigate the role of mediators involved in the development of airway remodeling to enhance asthma therapy.

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“…Clinically, TNF-α has been proposed as a target for asthma therapy: in patients with severe asthma, elevated levels of TNF-α in bronchoalveolar lavage (BAL) fluid have been reported [25]. Antibodies targeting TNF-α, as well as a fusion protein of the type II TNF receptor with the Fc region of human IgG, are the therapeutics that have been used in clinical trials for treatment of asthma.…”

Section: Asm-mediated Modulation Of Inflammationmentioning

confidence: 99%

Targeting airway smooth muscle in airways diseases: an old concept with new twists

Koziol‐White

Damera

Panettieri³

2011

Expert Review of Respiratory Medicine

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Biologic therapies for asthma

Cited by 12 publications

References 35 publications

Anti-Inflammatory Effects of the Neurotransmitter Agonist Honokiol in a Mouse Model of Allergic Asthma

Anti-Inflammatory Effects of the Neurotransmitter Agonist Honokiol in a Mouse Model of Allergic Asthma

Recent Advances in Mechanisms and Treatments of Airway Remodeling in Asthma: A Message from the Bench Side to the Clinic

Targeting airway smooth muscle in airways diseases: an old concept with new twists

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