Trigger 6: Animal models

Question 1

How can animal models be used to help to understand/ develop treatment for IPF?

Answer 1

• Disease understanding at a cellular and molecular level
• Dose selection for humans
• Drug safety
• Drug structure activity relationship

Question 2

What is the ideal IPF model?

Answer 2

• Mimics key pathological features of human disease
• Progressive/fatal
• Paucity of granulocytic inflammation
• Prone to acute exacerbation

Question 3

What is the ideal IPF model for drug discovery?

Answer 3

o Large therapeutic window
o High throughput
o Reproducible
o Low resource intensity

Question 4

general pros of animal models

Answer 4

• more ethical the testing on humans
• controlled environment (reproducible)
• cheap to look after
• can often mimic human disease

Question 5

general cons of animal models

Answer 5

• 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

Question 6

name the five types of animal models

Answer 6

1) bleomycin
2) transgenic models
3) FITC
4) Irradiation
5) Silica

Question 7

Bleomycin is

Answer 7

a medication used to treat cancer (e.g. non-hodgkins)

Question 8

The bleomycin model of IPF

Answer 8

it is given to mice, rats and rabbits etcs intratracheally
causes a fibrotic response within a few weeks
doubling lung collagen

Question 9

advantages of bleomycin model

Answer 9

• Best characterised model
• Clinical relevance
• Multiple delivery routes

Question 10

disadvantages of bleomycin model

Answer 10

• Fibrosis does not develop in all animals
• Long timeframe
• Disease may be self-limiting

Question 11

transgenic model (2)

Answer 11

1) Pulmonary specific- in vivo, explore molecular mechanisms

2) Virus targeted- v

Question 12

advantages of transgenic models- Pulmonary specific

Answer 12

Gene expression can be controlled so pulmonary fibrosis regression can be examined

Question 13

disadvantage of transgenic models- Pulmonary specific

Answer 13

Condition does not mimic clinical observation of PF in adulthood

Question 14

advantages of transgenic model- Virus targeted

Answer 14

valuable for understanding pathogenesis of PF and understanding gene products of initiation and maintenance of PF

Question 15

disadvantages of transgenic model- Virus targeted

Answer 15

promote vigorous immune response,

Viruses are highly trophic for epithelial cells

Question 16

FITC stands for

Answer 16

fluorescein isothiocyanate

Question 17

FITCs animal model

Answer 17

Intratracheal administration- destroy lung architecture and induces fibrosis

Question 18

advantages of FITC model

Answer 18

Able to visualise areas of lung with IF imaging, persistent response, not self limiting

Question 19

disadvantage of FITC model

Answer 19

expensive

Question 20

irradiation animal moel

Answer 20

Single dose whole body irradiation resulting in IPF

Question 21

advantage of irradiation

Answer 21

Well characterised differences between mice strains, clinically relevant

Question 22

disadvantage of irradiation

Answer 22

very expensive and time consuming

Question 23

silica model

Answer 23

mineral fibres cause fibrotic nodules- mimics occupational exposure

Question 24

advantage of silica

Answer 24

Persistent, toxic inflammatory response

Question 25

disadvantage of silica

Answer 25

Method of exposure not replicable, expensive and lengthy