At Aquilo, we have vast experience with using guinea pigs and mice as model animals for testing the effectiveness of your compound against asthma, COPD and lung fibrosis.
Due to the pathological and pathophysiological similarities, guinea pigs are excellent as a model system for studying lung diseases such as asthma and COPD. The airway physiology and pathophysiology of lung diseases is comparable to that in humans.
As a CRO we can facilitate you in makin custom study designs and are open to implementing tailor made models.
Contact us to see how we can implement your compound in one of our models.

The features regarding the asthma mouse model are as followed:

  • Ovalbumin, house dust mite exposure or mixed allergens
  • Airway eosinophilia, cytokine production,
  • Airway hyperresponsiveness,
  • Airway smooth muscle thickening,
  • Goblet cell hyperplasia,
  • Subepithelial fibrosis,
  • Pulmonary vascular remodeling.

We have previously shown efficacy of anticholinergics, in particular M3 selective anticholinergics in the asthma mouse model by using C57Bl/6 mice.
For this model however both  C57Bl/6 and Balb/c mice can be used.
Balb/c mice have more profound eosinophilic inflammation, whereas the remodeling is comparable between these strains. See publication

For the in vivo COPD mouse we have the following models:
-Mouse model of cigarette smoke-induced inflammation

Features:

  • Infiltration of macrophages and neutrophils in the lung,
  • Cytokine production and growth factor release.

We have previously shown efficacy of anticholinergics, in particular M3 selective anticholinergics, in this COPD mouse model.

-Mouse model of elastase-induced emphysema

Features:

  • Increase in mean linear intercept – emphysema,
  • Cytokine production in the lung,
  • Decrease in specific epithelial and endothelial cell markers. See publication

Features:

  • Single bleomyocin or silica exposure,
  • Lung function analysis by FlexiVent,
  • Inflammation (cell differentials, cytokine release),
  • Fibronectin and collagen expression,
  • Hydroxyproline analysis,
  • Masson-Goldner staining. See publication

A feature of acute LPS exposure to the lungs is neutrophilic inflammation in the bronchoalveolar lavage fluid.
Thus, effectiveness of your compound can be tested against this neutrophilic inflammation.
We have previously demonstrated efficacy of anticholinergics and β2 agonists in this model. See publication

Features of chronic LPS exposure to the lungs are:

  • Twice weekly LPS challenges for 12 weeks,
  • Tissue neutrophilia and cytokine production,
  • Collagen deposition around the small airways,
  • Mucus gland hypertrophy, goblet cell hyperplasia,
  • Right ventricle remodeling.

We have previously shown efficacy of anticholinergics and GSK-3 inhibitors in this model. See publication

Guinea pigs are excellent as a model system for asthma.
Using a balloon catheter  to measure lung function online in freely moving unrestrained animals. Not only can the hyperresponsiveness to histamine be tested, but also the nature and size of the early and late asthmatic response can be measured including effects of pharmacological treatments here on.

Features:

  • Single ovalbumin challenge,
  • Early and late asthmatic reactions,
  • Airway hyperresponsiveness to histamine (PC100) after the early and late asthmatic reaction,
  • Influx of inflammatory cells, notably eosinophils, and expression of pro-inflammatory cytokines.

We have previously demonstrated efficacy of bronchodilator drugs (β2 agonists, anticholinergics, Rho-kinase inhibitors) and anti-inflammatory drugs (glucocorticopsteroids, arginase inhibitors) in this model. See publication

Features:

  • Weekly ovalbumin challenges for 12 weeks,
  • Eeosinophilic airway inflammation in the large and the small airways,
  • Airway smooth muscle thickening,
  • Mucus gland hypertrophy, goblet cell differentiation and MUC5A/C expression
  • Increased airway contractility.

We have previously demonstrated efficacy of anticholinergics, glucocorticosteroids and arginase inhibitors against allergen induced remodeling using this model and can test your compound in a similar way.

clear advantage of the guinea pig is that both cartilaginous (large airways) and non-cartilaginous airways (small airways) can be identified which show differential characteristics of inflammation and remodeling, which is also observed in humans and cannot be modeled in mice.