Mouse Models of Alopecia Areata: C3H/HeJ Mice Versus the Humanized AA Mouse Model

Gilhar, Amos; Britva, Rimma Laufer; Keren, Aviad; Paus, Ralf

doi:10.1016/j.jisp.2020.05.001

Cited by 7 publications

(3 citation statements)

References 67 publications

(82 reference statements)

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“…As the first study to investigate itaconate derivatives for treating hair loss, our results support their continued investigation as a treatment for alopecia areata. Besides initiating human studies, performing studies in C3H/HeJ or humanized mouse models of alopecia areata ( 53 ) may further determine the utility of itaconate-based drugs for this condition. Hair cycling and growth involves interactions between multiple cell types and structures, such as hair follicle stem cells, dermal papilla cells, dermal sheath cells, immune cells, adipose tissue, nerves, and vasculature.…”

Section: Discussionmentioning

confidence: 99%

Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata

et al. 2022

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Alopecia areata is a chronic hair loss disorder that involves autoimmune disruption of hair follicles by CD8+ T cells. Most patients present with patchy hair loss on the scalp that improves spontaneously or with topical and intralesional steroids, topical minoxidil, or topical immunotherapy. However, recurrence of hair loss is common, and patients with extensive disease may require treatment with oral corticosteroids or oral JAK inhibitors, both of which may cause systemic toxicities with long-term use. Itaconate is an endogenous molecule synthesized in macrophages that exerts anti-inflammatory effects. To investigate the use of itaconate derivatives for treating alopecia areata, we designed a prodrug of 4-methyl itaconate (4-MI), termed SCD-153, with increased lipophilicity compared to 4-MI (CLogP 1.159 vs. 0.1442) to enhance skin and cell penetration. Topical SCD-153 formed 4-MI upon penetrating the stratum corneum in C57BL/6 mice and showed low systemic absorption. When added to human epidermal keratinocytes stimulated with poly I:C or IFNγ, SCD-153 significantly attenuated poly I:C-induced IL-6, TLR3, IL-1β, and IFNβ expression, as well as IFNγ-induced IL-6 expression. Topical application of SCD-153 to C57BL/6 mice in the resting (telogen) phase of the hair cycle induced significant hair growth that was statistically superior to vehicle (DMSO), the less cell-permeable itaconate analogues 4-MI and dimethyl itaconate, and the JAK inhibitor tofacitinib. Our results suggest that SCD-153 is a promising topical candidate for treating alopecia areata.

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Section: Discussionmentioning

confidence: 99%

Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata

et al. 2022

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“… 55 However, C3H/HeJ mice develop spontaneous AA at a very low frequency, with histologic features that do not resemble those in human AA. 56 Human AA is characterized by intra- and pre-follicular infiltration of CD4 + and CD8 + T lymphocytes. In murine AA, inflammatory cells infiltrate to the distal follicle and can reach the bulge.…”

Section: Mouse Vs Human Hairmentioning

confidence: 99%

“…In murine AA, inflammatory cells infiltrate to the distal follicle and can reach the bulge. Key differences between the C3H/HeJ model and human AA pathobiology, genetics, and immunobiology have been reviewed, 56 , 57 questioning the suitability of the mouse model to validate the efficacy of therapeutic compounds for human AA. For this reason, a humanized mouse model has been generated for preclinical studies.…”

Section: Mouse Vs Human Hairmentioning

confidence: 99%

The Emergent Power of Human Cellular vs Mouse Models in Translational Hair Research

Castro

Portinha²,

Logarinho

2022

Stem Cells Translational Medicine

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Different animal models have been used for hair research and regeneration studies based on the similarities between animal and human skins. Primary knowledge on hair follicle (HF) biology has arisen from research using mouse models baring spontaneous or genetically engineered mutations. These studies have been crucial for the discovery of genes underlying human hair cycle control and hair loss disorders. Yet, researchers have become increasingly aware that there are distinct architectural and cellular features between the mouse and human HFs, which might limit the translation of findings in the mouse models. Thus, it is enticing to reason that the spotlight on mouse models and the unwillingness to adapt to the human archetype have been hampering the emergence of the long-awaited human hair loss cure. Here, we provide an overview of the major limitations of the mainstream mouse models for human hair loss research, and we underpin a future course of action using human cell bioengineered models and the emergent artificial intelligence.

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Acquired Disorders of Hair

Harries,

Holmes,

McMichael

et al. 2024

Rook's Textbook of Dermatology

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This chapter reviews acquired hair disorders, including common scarring and non‐scarring alopecia presentations, conditions characterised by excessive body hair growth and acquired hair shaft disorders. We also describe the biology of normal hair follicles, including structure, hair cycle control and immunity, to better understand the mechanisms underlying these conditions. We present methods for clinical assessment, recommended investigation and management of each disease, and present summaries of frequently used therapeutics and cosmetic options employed when treating these problems.

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Mouse Models of Alopecia Areata: C3H/HeJ Mice Versus the Humanized AA Mouse Model

Cited by 7 publications

References 67 publications

Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata

Topical SCD-153, a 4-methyl itaconate prodrug, for the treatment of alopecia areata

The Emergent Power of Human Cellular vs Mouse Models in Translational Hair Research

Acquired Disorders of Hair

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