Dose-response effects of TPI ASM8 in asthmatics after allergen

Gauvreau, Gail M.; Pageau, R.; Séguin, Rosanne; Carballo, D. Calero; Gauthier, Jordan; Danjou, H.; Campbell, Heather; Watson, Rick; Mistry, Mahek; Parry-Billings, Mark; Killian, Kieran J.; Renzi, Paolo

doi:10.1111/j.1398-9995.2011.02638.x

Cited by 57 publications

(38 citation statements)

References 32 publications

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“…Along with future work to determine the mechanism of the foamy appearance, work needs to include studies in human monocytes and macrophages or if possible human AM. To date, delivery of inhaled AON to humans has not resulted in increased macrophage numbers recovered from induced sputum, 41 but further biochemical characterization of these macrophages has yet to be undertaken.…”

Section: Discussionmentioning

confidence: 99%

The effect of in vitro exposure to antisense oligonucleotides on macrophage morphology and function

Brasey

Igue

Djemame

et al. 2011

J Nucleic Acids Invest

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Antisense oligonucleotides (AON) delivered via inhalation are in drug development for respiratory diseases. In rodents and monkeys, repeated exposure to high doses of inhaled phosphorothioate (PS) AON can lead to microscopic changes in the lungs, including accumulation of alveolar macrophages in the lower airway that have a foamy appearance. The functional consequences that result from this morphological change are unclear as there is controversy whether the vacuoles/inclusion bodies reflect normal clearance of the inhaled AON or are early indicators of lung toxicity. The morphological and functional responses of macrophage to PS AON were characterized in vitro using the comparator drug amiodarone, as a known inducer of foamy macrophages.

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Section: Discussionmentioning

confidence: 99%

The effect of in vitro exposure to antisense oligonucleotides on macrophage morphology and function

Brasey

Igue

Djemame

et al. 2011

J Nucleic Acids Invest

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“…TPI ASM-8, an antisense oligonucleotide, targets against CCR3, which mediates the effect of some eosinophil chemoattractant [51]. TPI ASM-8 has been shown to significantly reduce allergen airway eosinophilia in 14 stable, mild allergic asthmatics in a dose-dependent manner [52,53]. Doubling the dose of TPI ASM-8 reduced post-allergen AHR to methacholine [53].…”

Section: New Approachesmentioning

confidence: 99%

“…TPI ASM-8 has been shown to significantly reduce allergen airway eosinophilia in 14 stable, mild allergic asthmatics in a dose-dependent manner [52,53]. Doubling the dose of TPI ASM-8 reduced post-allergen AHR to methacholine [53]. Another approach is to use small interfering (si)RNA molecules against IL-5 or eotaxin to prevent protein transcription.…”

Section: New Approachesmentioning

confidence: 99%

Anti-interleukin-5 therapy in severe asthma

Garcia

Taillé

Laveneziana

et al. 2013

European Respiratory Review

112

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Asthma is a chronic inflammatory disorder of the airways that leads to acute symptoms, exacerbations and sometimes, for a small part of the asthmatic population, fatal or near-fatal exacerbations.This as yet significant minority of individuals present with severe asthma and have persisting daily symptoms, and exacerbations despite compliance with high doses of inhaled steroids and additional treatment. For more than a decade, the pharmacological management of patients with severe asthma has focused on evaluating specific cytokines. The rationale of this approach is based on the distinguished key role played by eosinophils in the asthma inflammatory processes. Eosinophils are recruited from the circulation to airways where they cause airway damage via different mechanisms. Eosinophils are regulated in terms of their recruitment, activation, growth, differentiation and survival by interleukin (IL)-5. Abundant data from in vitro experiments, animal models and clinical trials has confirmed that IL-5 inhibition may be an effective approach for the treatment of asthma, especially severe asthma. Interfering with eosinophil function or reducing their numbers has been one of the most important goals of therapeutic monoclonal antibodies, which target cytokine receptor interactions in asthma, particularly IL-5. This review will consider new treatments options for severe asthma, particularly those targeting IL-5, that have already been evaluated in clinical trials in asthmatic patients. @ERSpublications Rationale, recent advances and future developments of anti-IL-5 therapy in patients with severe asthma http://ow.ly/n3viv

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“…Recent reports continue to show variable results, ranging from no effect following treatment with a heparin derivative molecule [61] or anti-IL13 therapies [62], to a trend with single-dose combined antihistamine and antileukotriene [63], to significant inhibition with an antisense oligonucleotide molecule [64,65]. These data, in combination with other data collected during allergen challenge studies, should help in delineating the mechanism of allergic asthma and how to best treat the disease.…”

Section: Reviewmentioning

confidence: 80%

Past, present and future uses of methacholine testing

Davis¹,

Cockcroft

2012

Expert Review of Respiratory Medicine

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Methacholine challenge testing is a valuable diagnostic and research tool used by clinicians to assist in the diagnosis of asthma, and by researchers to understand disease pathophysiology and assess novel therapeutic efficacy. The use of methacholine challenge in asthma relates to its direct effect on airway smooth muscle (i.e., bronchoconstriction) as a measure of airway hyperresponsiveness, a cardinal feature of asthma. Airway hyperresponsiveness has been documented in other airway disorders, including chronic obstructive pulmonary disease, cystic fibrosis and allergic rhinitis; however, there is little clinical application of methacholine challenge in these conditions as a diagnostic or disease management tool. The authors will review the aspects of methacholine challenge testing, as they relate to asthma, and point out its usefulness in clinical research. A brief review of past (historical) uses and speculation as to the future uses of methacholine challenge will also be discussed.

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Dose-response effects of TPI ASM8 in asthmatics after allergen

Abstract: TPI ASM8 attenuated a broad range of inflammatory and physiological changes after AIC, suggesting that CCR3, IL-3, and GM-CSF also are important targets for the management of asthma.

Cited by 57 publications

References 32 publications

The effect of in vitro exposure to antisense oligonucleotides on macrophage morphology and function

The effect of in vitro exposure to antisense oligonucleotides on macrophage morphology and function

Anti-interleukin-5 therapy in severe asthma

Past, present and future uses of methacholine testing

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