Chemotherapy-induced Alopecia Mouse Model / Overview
Introduction / Chemotherapy-induced Alopecia Mouse Model
In clinical oncology, chemotherapy-induced alopecia (ChIA) is still an open issue.
Psycho-social stress is brought on by hair loss, and some patients will even decline treatment out of concern for their hair. Regrowth can be seen 3–6 months after chemotherapy ends, and ChIA is typically reversible. However, there have been more and more reports of permanent ChIA, which is defined as no hair growth after six months of stopping chemotherapy. The underlying patho-physiology, particularly for permanent ChIA, remains insufficiently understood and is associated with a lack of effective preventive treatment.
Alopecia preclinical models were developed at Imavita for R&D purpose.
Protocol summary / Chemotherapy-induced Alopecia Mouse Model
Chemical back hair depilation with chemotherapy at day 10.
Mice details: Immunocompetent strain in SPF facility A1.
Treatments administration: test drugs via oral, IP, IV, SC or topical routes.
Monitoring for maximum 40 days: bodyweights, hair growth scoring, visual macroscopic scoring (erythema, scaling), digital pictures.
Evaluation of hair cycle: histology (HES / IF / IHC), genes expression (qPCR).
Typical results / Chemotherapy-induced Alopecia Mouse Model
Chemotherapy-induced Alopecia Mouse Model
Parameter
Group control
No induction
Test group
CYP induction
Bodyweight
NE (No Effect)
NE or slight decrease
Skin hair score
(visual scoring
or SkinColorCatch®
(melanin index))
Maximal after 10 to 15 days
Low score maintained after CYP induction
Mouse day 0
(Depilation d10 / CYP d0)
Mouse day 16
(Depilation d26 / CYP d16)
Chemotherapy-induced Alopecia Mouse Model / Conclusion
Preclinical animal models of alopecia are used to study the underlying mechanisms of the disease and to test potential treatments before they are evaluated in clinical trials involving humans. 8 to 10 animals per group are generally sufficient to underline anti-alopecia effect of new therapeutics (based on difference about 25 to 30%). Various drugs can be used as alopecia inhibitors for reference or comparison (ciclosporin / minoxidil / JAKi).
By using this model, researchers can gain a better understanding and investigate potential anti-alopecia therapies. However, it’s important to note that pre-clinical mouse models are only approximations of the human condition and may not completely reflect the human specificity.
Cautions to be taken on this model:
Does PK of the test drug need to be evaluated first?
Drug pharmacokinetics / ADME / transcutaneous passage should be known to optimize drug dosing whatever the route. This is recommended, but not required.
What excipient should be used for topical route?
Use of previously untested excipients should be avoided as they could cause false positive, false negative or local irritation. In any case, excipient negative group will be included.
Which requirements are needed for formulation?
Fomulation physico-chemistry should be well known (pH, osmolarity, etc…) as these factors can impact efficacy testing, principally for topical applications.
Project duration and follow-up:
Approximated duration 60 days
for in vivo experiment until draft report for in vivo.various
Do not hesitate to contact us if you need more information or a quotation on this model.
Chemotherapy-induced Alopecia Mouse Model / Bibliography
Lin, X., Zhu, L. & He, J. Morphogenesis, Growth Cycle and Molecular Regulation of Hair Follicles. Front. Cell Dev. Biol. 10, 1–11 (2022).
Yoon, J.-S. et al. Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles after Chemotherapy. J. Invest. Dermatol. 136, 584–592 (2016).
Paus, R., Haslam, I. S., Sharov, A. A. & Botchkarev, V. A. Pathobiology of chemotherapy-induced hair loss. Lancet Oncol. 14, e50–e59 (2013).
Chon, S. Y., Champion, R. W., Geddes, E. R. & Rashid, R. M. Chemotherapy-induced alopecia. J. Am. Acad. Dermatol. 67, e37–e47 (2012).
Hendrix, S., Handjiski, B., Peters, E. M. J. & Paus, R. A Guide to Assessing Damage Response Pathways of the Hair Follicle: Lessons From Cyclophosphamide-Induced Alopecia in Mice. J. Invest. Dermatol. 125, 42–51 (2005).
Porter, R. M. Mouse models for human hair loss disorders. J. Anat. 202, 125–31 (2003).
Müller-Röver, S. et al. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J. Invest. Dermatol. 117, 3–15 (2001).
Paus, R., Handjiski, B., Eichmüller, S. & Czarnetzki, B. M. Chemotherapy-induced alopecia in mice: Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by dexamethasone. Am. J. Pathol. 144, 719–734 (1994).
