Preclinical models for pulmonary disease and drug delivery
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The Allergenix sheep models of respiratory disease provide a platform for realistic in vivo drug discovery studies and preclinical testing in a highly translational large animal model system.

These models have been used to improve understanding of the pathways underlying human disease pathogenesis, and to discover more effective therapies to prevent or halt the progression of disease.

Sheep model of allergic asthma (proprietary Allergenix model)

  • closely parallels human allergic asthma (and superior to the well known Ascaris-sensitive sheep asthma model)
  • induced by active sensitisation and lung challenge with house dust mite (HDM), the most prominent human allergen
  • acute and chronic models of disease
  • characterised by: Th2 immune profile; eosinophil inflammation, mast cells; airway wall remodelling (chronic); decline in lung function (chronic)
  • responsive to (human) anti-asthma medications
  • customised model system: whole lung or targeted segmental lobes for challenge and/or treatment studies
  • model utility: disease pathogenesis studies; efficacy of anti-asthma treatments/therapies

Sheep model of COPD/emphysema

  • induced by lung exposures to elastase and LPS
  • characterised by: neutrophil and macrophage inflammation; tissue damage consistent with emphysema (enlargement of air spaces and alveolar wall destruction); lung function decline
  • model utility: disease pathogenesis studies; efficacy of treatments/therapies to alter inflammation, and rate of tissue destruction and lung function decline

Sheep model of pulmonary fibrosis

  • induced by lung exposures to bleomycin
  • characterised by: inflammation; fibrosis and collagen deposition; lung function decline
  • responsive to (human) anti-fibrosis medications
  • model utility: disease pathogenesis studies; therapeutic intervention studies to change the course of fibrosis and rate of lung function decline

Sheep model of Respiratory Syncytial Virus (RSV) Infection

  • induced by RSV inoculation/infection of the lungs: perinatal infection model
  • clinical correlates with human RSV infection
  • model utility: development and testing of new treatments, drug delivery, and therapeutic strategies

Sheep model of lung cancer

  • induced by lung inoculation/infection with the Jaagsiekte sheep beta-retrovirus (JSRV) to individual lung segments
  • shows similarities in clinical presentation and histology to human lung adenocarcinoma
  • in vivo and in vitro/ex vivo experimental systems available to study tumorigenesis
  • model utility: disease pathogenesis studies; novel molecular pathways involved in lung cancer as well as the assessment of potential targeted (inhalation) therapeutics

Other sheep respiratory disease models

  • acute lung inflammation: induced by LPS (or other suitable stimulants) exposure of the lungs
  • perinatal respiratory models: preterm lamb model of intrauterine inflammation; novel therapies to prevent newborn respiratory disease; cell therapies, drug administration
  • pulmonary arterial hypertension (PAH): induced by microspheres
  • capacity to develop unique models with unmet needs

 

 

Pulmonary drug administration

In vivo capabilities

In vitro and ex vivo capabilities