Bile duct ligation in animal models

Animal testing is a crucial aspect of drug development, mandated by the FDA for all premature drugs in development. However, a critical question arises: how can we be sure that the pathology observed in rodents is reflective of the same pathology in humans? This is a significant concern for the medical community because of the potential for negative consequences if clinical trials are based on inaccurate preclinical data as we see in humans. Why then is it so important to measure biomarker formations in rodents? Because it matters whether it mimics the right pathology.

 Example for bridging preclinical and clinical practice. Bile duct ligation: a preclinical model of liver fibrosis.

The process of transitioning from preclinical to clinical trials is critical to success. Histological stages are built on human tissue sections and used for comparison to create an appropriate animal model. However, none of the existing rodent models currently develop nonalcoholic steatohepatitis (NASH) as seen in humans. This discrepancy raises concerns regarding the usefulness of rodent models for preclinical studies.

Despite these concerns, it is still essential to measure biomarker formations in rodents. The reason being, it matters whether the biomarker mimics the correct pathology. Nordic Bioscience has demonstrated increasing formation of both type III collagen (interstitial matrix) and type IV collagen (basement membrane) with continued injury in a rat bile duct ligation model. Collagen III has been shown to be upregulated in human liver fibrosis, including NASH, and is associated with increased severity. On the other hand, collagen IV is a measure of early fibrosis remodeling.

 Bile duct ligation: a preclinical model of liver fibrosis

It is critical to understand fibrosis remodeling during disease progression in both animals and humans. With Nordic Bioscience's biomarkers, researchers can improve translation between the preclinical and clinical practice. The use of biomarkers enables researchers to track disease progression and evaluate the effectiveness of potential treatments accurately. Moreover, they can also help identify patients who are likely to respond positively to a particular therapy.

Animal testing remains a critical aspect of drug development, it is essential to understand rodent model limitations. Biomarkers offer an effective way to track the progression of disease accurately. We can identify patients likely to benefit from a specific treatment and improve the transition from preclinical to clinical trials. By leveraging biomarkers in both animal and human models, we can make sure that the right therapy is provided to the right patient—at the right time.

Learn more about our liver fibrosis biomarkers.