Trigger 6: Animal models Flashcards
How can animal models be used to help to understand/ develop treatment for IPF?
- Disease understanding at a cellular and molecular level
- Dose selection for humans
- Drug safety
- Drug structure activity relationship
What is the ideal IPF model?
- Mimics key pathological features of human disease
- Progressive/fatal
- Paucity of granulocytic inflammation
- Prone to acute exacerbation
What is the ideal IPF model for drug discovery?
o Large therapeutic window
o High throughput
o Reproducible
o Low resource intensity
general pros of animal models
- more ethical the testing on humans
- controlled environment (reproducible)
- cheap to look after
- can often mimic human disease
general cons of animal models
- may not mimic human disease exactly
- may not react tot drugs ins are way as humans
- contamination easy
- often knock-out/ knock-i mice are not viable
name the five types of animal models
1) bleomycin
2) transgenic models
3) FITC
4) Irradiation
5) Silica
Bleomycin is
a medication used to treat cancer (e.g. non-hodgkins)
The bleomycin model of IPF
it is given to mice, rats and rabbits etcs intratracheally
causes a fibrotic response within a few weeks
doubling lung collagen
advantages of bleomycin model
- Best characterised model
- Clinical relevance
- Multiple delivery routes
disadvantages of bleomycin model
- Fibrosis does not develop in all animals
- Long timeframe
- Disease may be self-limiting
transgenic model (2)
1) Pulmonary specific- in vivo, explore molecular mechanisms
2) Virus targeted- v
advantages of transgenic models- Pulmonary specific
Gene expression can be controlled so pulmonary fibrosis regression can be examined
disadvantage of transgenic models- Pulmonary specific
Condition does not mimic clinical observation of PF in adulthood
advantages of transgenic model- Virus targeted
valuable for understanding pathogenesis of PF and understanding gene products of initiation and maintenance of PF
disadvantages of transgenic model- Virus targeted
promote vigorous immune response,
Viruses are highly trophic for epithelial cells
FITC stands for
fluorescein isothiocyanate
FITCs animal model
Intratracheal administration- destroy lung architecture and induces fibrosis
advantages of FITC model
Able to visualise areas of lung with IF imaging, persistent response, not self limiting
disadvantage of FITC model
expensive
irradiation animal moel
Single dose whole body irradiation resulting in IPF
advantage of irradiation
Well characterised differences between mice strains, clinically relevant
disadvantage of irradiation
very expensive and time consuming
silica model
mineral fibres cause fibrotic nodules- mimics occupational exposure
advantage of silica
Persistent, toxic inflammatory response
disadvantage of silica
Method of exposure not replicable, expensive and lengthy
