Pharmacological Validation of SSc-ILD Mouse Model Bleomycin-Induced by Osmotic Minipump

Francesca Ravanetti,Erica Ferrini,Luisa Ragionieri,Zahra Khalajzeyqami,Maria Nicastro,Yanto Ridwan,Alex Kleinjan,Gino Villetti,Andrea Grandi,Franco Fabio Stellari

crossref（2021）

University of Parma | University of Bologna | Erasmus University Rotterdam | Chiesi (Italy)

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Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by an excessive production and accumulation of collagen in the skin and internal organs often associated with interstitial lung disease (ILD). The unknown pathogenetic mechanisms of SSc-ILD and the lack of animal models mimicking the features of the human disease contribute to create a gap between the selection of antifibrotic drug candidates and effective therapies. Nintedanib (NINT) was used as a tool compound to validate the pharmacological response either on lung or skin fibrosis in a SSc-ILD mouse model. The model is based on the continuous infusion of bleomycin (BLM) by osmotic minipumps for 1 week in the C57BL/6 female mice. Longitudinal Micro-CT analysis highlighted a significant slowdown in lung fibrosis progression after NINT treatment, then confirmed by histology. However, no significant effect was observed on lung hydroxyproline content, inflammatory infiltrate and skin lipoatrophy. The modest pharmacological effect reported reflects the clinical outcome, lighting up the reliability of this model to serve as secondary screening to profile the best clinical drug candidates. Moreover, we have underlined the pivotal role of Micro-CT imaging, together describing the relevant readouts and the importance of their validation prior to use for drug discovery.

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Systemic Sclerosis

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