Assessment of multiple pharmacological mechanisms in the ascaris sensitive sheep model of allergic asthma

Michael Caniga,Lily Y Moy,Malgorzata A Gil,Michael A Crackower,William M Abraham,Janice D Woodhouse,Robbie Mcleod,Alan Wilhelm,Thomas Miller,Milenko Cicmil

doi:10.1186/1476-9255-10-s1-p15

Michael Caniga, Lily Y Moy + Show 8 more

Open Access

https://doi.org/10.1186/1476-9255-10-s1-p15

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Abstract

Background Asthma is a multifaceted disease that presents with a combination of reversible bronchoconstriction, inflammation, and airway remodeling. Historically, a variety of in vivo models have been used by preclinical investigators as surrogates for the disease. However, many of these models have significant limitations. For example, rodent models relying solely on TH2 mediated respiratory inflammation have inadequate predictability and clinical translatability because they can only recapitulate partial aspects of the human disease. In order to align with human Phase I allergen challenge experiments we used ascaris sensitive sheep model. This model enables us to investigate role of different mechanisms on early and late asthmatics responses.

Highlights

Asthma is a multifaceted disease that presents with a combination of reversible bronchoconstriction, inflammation, and airway remodeling
In order to align with human Phase I allergen challenge experiments we used ascaris sensitive sheep model
Novel anti-inflammatory targets such as Chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2) inhibitor, MK7246, show little inhibition of the early airway response (EAR) at low doses and blocked the late airway response (LAR) and airway hyperreactivity (AHR)

Summary

Background

Asthma is a multifaceted disease that presents with a combination of reversible bronchoconstriction, inflammation, and airway remodeling. A variety of in vivo models have been used by preclinical investigators as surrogates for the disease. Many of these models have significant limitations. Rodent models relying solely on TH2 mediated respiratory inflammation have inadequate predictability and clinical translatability because they can only recapitulate partial aspects of the human disease. In order to align with human Phase I allergen challenge experiments we used ascaris sensitive sheep model. This model enables us to investigate role of different mechanisms on early and late asthmatics responses

Methods and materials

Results

Conclusion