Aragen Bioscience has a portfolio of in vivo fibrosis models and the world-class expertise to support you during the development of your therapeutic. In hundreds of studies over the course of a decade, we have evaluated the efficacy of small molecules and biologic test compounds in a variety of models, ultimately resulting in multiple INDs for our clients.
Nonalcoholic Steatohepatitis (NASH)
Nonalcohlic fatty liver disease (NAFLD), a common form of chronic liver disease caused by over nutrition, is characterized by the accumulation of lipids in the hepatocytes and is closely associated with obesity, hyperlipidemia and type-2 diabetes. NAFLD can manifest as simple steatosis or progress to nonalcoholic steatohepatitis (NASH), a more severe form of NAFLD characterized by hepatocellular damage (ballooning), inflammation and fibrosis. Although not all patients with NAFLD develop liver complications, patients with NASH are at increased risk of progression to cirrhosis, hepatocellular carcinoma and end-stage liver disease.
Aragen has developed a mouse and rat model of NASH that recapitulates many of the attributes of human NASH. In this model, substantial fibrosis develops within 12 weeks, a significantly shorter time frame than with obesogenic diets. In addition, this model is not complicated by extensive weight loss, as observed with the MCD or CDAA diets, or increased mortality, as seen in the STAM™ mouse model. Combined with a variety of end-point assays, including Aragen’s FibroPanel™ gene expression analysis, our NASH model can provide a robust assessment of multiple parameters of NASH, including steatosis, inflammation and fibrosis.
Bleomycin-Induced Lung Fibrosis
Idiopathic pulmonary fibrosis (IPF), the most common form of the idiopathic interstitial pneumonias, is a chronic, progressive, irreversible, and typically lethal lung disease. Pirfenidone and Nintedanib were approved in 2014 in the US, where the incidence of IPF has been increasing.
Bleomycin-induced pulmonary fibrosis has been a useful pre-clinical model in several species and is most prevalent in rodent models to evaluate potential prophylactic and therapeutic drugs for IPF. As a tissue injury and repair model, bleomycin has contributed significantly to studies of the pathobiology of pulmonary fibrosis. The induction and progression of the disease in rodents is of a short duration, making it a practical model for evaluating test compounds in preclinical research. Although major drawbacks for this model have been its high mortality rate and inconsistency in the induction of disease, our extensive experience with this model has led to a proven track record of highly reproducible and successful preclinical studies.
- Pulmonary fibrosis is induced in mice and rats by the instillation of clinical grade bleomycin into the lungs by the oralpharyngeal route or osmotic pump
- Models include therapeutic as well as prophylactic study designs spanning from two weeks to five weeks post-bleomycin administration
- Output from the studies can range from basic readouts of in-life parameters of clinical symptoms, bronchoalveolar lavage (BAL) fluid analysis, and hydroxyproline assays of lungs to more complex functional readouts using FlexiVent and airway hyper-reactivity using unrestrained whole body plethysmography
Analysis to Detect Fibrotic Symptoms
- Body weight
- Daily activity levels
- Lung weights
- Leukocyte/differential count in Bronchoalveolar Lavage (BAL) harvest
- Flexivent-lung function measurements
- Hypoxia related parameters
- Whole-body plethysmography
- Hydroxyproline or Sircol collagen assay
- Serum analysis
- Others: Organ harvest for histopathology
Aragen has a range of other fibrosis models as well:
- Lung fibrosis model in C57BL/6 mice
- Silica-induced lung fibrosis model in mice
- CCL4 induced liver fibrosis in mice
- Dermal fibrosis in a scleroderma mouse model
- TAA-induced liver fibrosis in rats