TPI ASM8 Decreases Inflammatory Markers and Improves Airway Responsiveness in Asthmatics

Gauvreau, G.M.; Séguin, Rosanne; Carballo, D. Calero; Danjou, H.; Campbell, Heather; Watson, Renée O.; Parry-Billings, Mark; Killian, Kieran J.; Renzi, Paolo

doi:10.1016/j.jaci.2010.12.335

Cited by 1 publication

(2 citation statements)

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“…With respect to in vitro experiments, CSL 311 reduced the growth of BM- and PB-derived Eo/B-CFU that were incubated with IL-5/IL-3/GM-CSF pre- and 24 h post-Ag challenge in mild asthmatics [ 66 ]. In clinical studies with asthmatics, it was shown that treatment with an anti-sense TPI ASM8 (4 mg bid and 8 mg o.d.…”

Section: Targets Of Airway Eosinophilopoietic Processes In Asthmamentioning

confidence: 99%

“…In clinical studies with asthmatics, it was shown that treatment with an anti-sense TPI ASM8 (4 mg bid and 8 mg o.d. inhaled for 4 days) directed against the β common chain and CCR3, attenuated Ag-induced airway eosinophilia [ 66 , 74 ] as well as CCR3 + HPC and EoP numbers [ 67 ]. In addition, drug treatment significantly attenuated FEV 1 during the early and late asthmatic response and it improved the MCh PC 20 24 post-Ag ( Table 1 ).…”

Section: Targets Of Airway Eosinophilopoietic Processes In Asthmamentioning

confidence: 99%

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Eosinophil Lineage-Committed Progenitors as a Therapeutic Target for Asthma

Salter

Sehmi

2021

Cells

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Eosinophilic asthma is the most prevalent phenotype of asthma. Although most asthmatics are adequately controlled by corticosteroid therapy, a subset (5–10%) remain uncontrolled with significant therapy-related side effects. This indicates the need for a consideration of alternative treatment strategies that target airway eosinophilia with corticosteroid-sparing benefits. A growing body of evidence shows that a balance between systemic differentiation and local tissue eosinophilopoietic processes driven by traffic and lung homing of bone marrow-derived hemopoietic progenitor cells (HPCs) are important components for the development of airway eosinophilia in asthma. Interleukin (IL)-5 is considered a critical and selective driver of terminal differentiation of eosinophils. Studies targeting IL-5 or IL-5R show that although mature and immature eosinophils are decreased within the airways, there is incomplete ablation, particularly within the bronchial tissue. Eotaxin is a chemoattractant for mature eosinophils and eosinophil-lineage committed progenitor cells (EoP), yet anti-CCR3 studies did not yield meaningful clinical outcomes. Recent studies highlight the role of epithelial cell-derived alarmin cytokines, IL-33 and TSLP, (Thymic stromal lymphopoietin) in progenitor cell traffic and local differentiative processes. This review provides an overview of the role of EoP in asthma and discusses findings from clinical trials with various therapeutic targets. We will show that targeting single mediators downstream of the inflammatory cascade may not fully attenuate tissue eosinophilia due to the multiplicity of factors that can promote tissue eosinophilia. Blocking lung homing and local eosinophilopoiesis through mediators upstream of this cascade may yield greater improvement in clinical outcomes.

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Section: Targets Of Airway Eosinophilopoietic Processes In Asthmamentioning

confidence: 99%