IMQ-induced Psoriasis Mouse Model / Overview

Dermatology preclinical efficacy Imavita

Introduction

Imiquimod (IMQ) produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis.
IMQ is a Toll-like Receptor (TLR7) agonist that can be applied to mouse skin to elicit erythema, scaling, epidermis hyperplasia, hyperkeratosis, parakeratosis and dermis inflammation. IMQ induces also IL-17/ IL-23 axis cytokines.
Imiquimod-Induced Psoriasis Mouse Model is a convenient, easy-to-use and affordable mouse model of acute inflammatory response, which is widely used in mechanistic pharmacology of pathology and as a pre-clinical animal model for drug screening and testing before clinical testing on volunteers psoriatic patients.

IMAVITA / Preclinical Imaging efficacy CRO

Protocol Summary

Immunocompetent strains topically applied with IMQ for 5 days
Evaluation of in vivo parameters:
– Bodyweights / Ear- back tickness
– Macroscopic scoring (erythema / scaling / etc…)
– Epidermis thickness using OCT
Evaluation of ex vivo parameters:
– Cytokines analysis / Cytometry
– Histology / Anatomo-pathological evaluation


Typical Results

Imavita / Preclinical imaging

EvaluationParameterControl group
(excipient)
Reference drug
(corticoid or immunosuppressor)
In vivoBodyweightLoss on 72h
(hydration necessary)
Loss on 72h
(hydration necessary)
Ear thickness
(calipering)
Increase >50%Increase 20-30%
Back skin scaling
(visual/macroscopical scoring)
Scaling moderate to importantSlight scaling
Back skin erythema
(visual/macroscopical scoring)
Erythema moderate to importantSlight erythema
Back skin thickness
(calipering)
Increase up to 50-100%Increase 20-30%
Ex vivo
(histology)
HES
(Comparison Ear)
Epidermis thicknessImportant increase vs. shamDecrease vs. excipient
Dermis thicknessImportant increase vs. shamDecrease vs. excipient
Dermis infiltrationImportant increase vs. shamDecrease vs. excipient
Other observationsHyperkeratosis with parakeratosis
Presence of microabscesses (Munro's microabscesses)
Parakeratosis absent or slight
Munro's microabscesses absent


IMQ-induced Psoriasis Mouse Model / Protocol

Immunomodulator induction / imiquimod topical application Immunocompetent rodent sp. (i.e. Balb/c & C57Bl6)
Environment status is important (SPF vs. non SPF conventional housing)
Evaluation of:
– Skin thickness measurement (ear / back)
– Erythema / Scaling (Clinical endpoints) / Total scoring
Blood samplings for circulating and skin biomarkers analysis (cytokines)
In vivo imaging (OCT)
Ex vivo imaging (histology HES / IHC)


IMQ-induced Psoriasis Mouse Model / Results

Sham vs. IMQ-induction:
– Increase of ear & back thickness
– Epidermis thickness / Dermis inflammation increase
IMQ-induction vs. reference drug:
– Reference drugs: corticoid (topical or oral) / immunosupressors (oral) / TNF inhibitors
– Reduction of ear & back thickness
– Epidermis thickness / Dermis inflammation decrease


IMQ-induced Psoriasis Mouse Model / Conclusion

Imiquimod-Induced Psoriasis Mouse Model is a first intention model, fast and reproducible used a routine model at Imavita.
8 subjects per group are generally sufficient to underline anti-psoriasis effect of new therapeutics (based on difference of at least 20 to 30% of ear / back thickness / epidermis thickness).
Cautions to be taken on this model:
Housing conditions are important (SPF vs. conventional). Imavita perform this experiment in conventional conditions where results are more reproducible.
– Use of previously untested excipients should be avoided via topical route as they could cause false positive, false negative or local irritation.
Formulation physico-chemistry must be well known (pH, osmolarity, etc…) as impact on results can be important.
– Drug pharmacokinetics / ADME / transcutaneous passage should be known to optimize dosing.

Do not hesitate to contact us if you need more information or a quotation on this model.