Scleroderma Model

Scleroderma is a multi-system autoimmune disease which is characterised by fibrosis of the skin and internal organs. Thickening and scarring of the skin are a hallmark of this condition. There is currently no cure for scleroderma. The symptoms of scleroderma can be managed by a range of treatments including immunomodulatory drugs.

At Charles River we have validated a bleomycin-induced skin scleroderma model which can be used to test the efficacy of lead compounds. In this model, repeated injections of bleomycin are administered intra-dermally causing macroscopic changes at the injection site.

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Study parameters include in-life scoring of clinical signs of scleroderma, i.e. skin erythema, thickening and scaling. Skin thickening starts to be visible on day 5 after the first bleomycin injection and peaks on day 28. Skin scaling can already be observed at day 5 after the first bleomycin injection. Moderate-to-marked scaling occurs from day 12 onwards and peaks on day 16. Skin erythema can be observed on day 5 after the first bleomycin administration and reaches its peak on day 9.

Hydroxyproline analysis can be used to quantify the amount of collagen in mouse skin biopsies, indicating the level of skin fibrosis.

Study Endpoints

  • Histopathology and quantification of cytokines in tissue homogenates
  • Hydroxyproline analysis
  • Blood and tissue sampling
  • PK/PD analysis

Validation Data

Graphs showing overall efficacy of Protopic on skin clinical scores.
Figure 1: Graphs showing overall efficacy of Protopic on skin clinical scores.

 

Histopathology showing the increase in dermal thickness in skin samples from bleomycin-treated animals compared to saline-treated controls

Figure 2: Histopathology showing the increase in dermal thickness in skin samples from bleomycin-treated animals compared to saline-treated controls.

 

Graphs showing that Protopic improves skin collagen content compared to vehicle
Figure 3: Graphs showing that Protopic improves skin collagen content compared to vehicle.