PATHOLOGIES > IPF – respiratory diseases
Biocellvia developed a strong expertise in compound validation assays for RESPIRATORY DISEASES such as pulmonary fibrosis.
Biocellvia’s IPF assay provides an accurate and reliable quantification of the severity of fibrosis, even at very low levels inaccessible by conventional scoring method.
IDIOPATHIC PULMONARY FIBROSIS
Current literature on pulmonary fibrosis observed in rodents and human clinical samples highlights the need to develop a fast, reliable and independent-observer assessment of histological analysis of fibrosis that cannot be satisfactorily achieved by conventional scoring evaluation.
Biocellvia’s pulmonary fibrosis validation assay development
- Based on a micro-computed histological analysis of digital images of full lung slices. Biocellvia proprietary software provides an accurate, very fast and automatic analysis of morphological changes in lung tissue achieved from the assessment of pulmonary tissue density (figure1).
Figure 1. BLM administration induced a dose dependant statistical significant increase of mean tissue density and high density frequency index (HDFm). Control group (n = 6), BLM groups (n = 12/group). p*<0.05, *** p<0.001, **** p<0.0001. A p-value <0.05 was considered significant.
- To visualize the heterogeneous distribution of lung fibrosis by means of the mapping of lung tissue density. A dedicated software was performed to realize 2D-reconstructed images of entire lung sections from pulmonary tissue density values (figure 2).
Figure 2. Representative original images and their corresponding 2D-reconstructed lung sections from saline and BLM-treated mice. 2D-reconstructed lung sections were realized from their individual tissue density values. Density values were graded in 20 classes of increasing values and pseudocolours were assigned from blue (low density values) to yellow (high density values) according to their classification. Note that high density values (yellow) were evidenced in alveolar parenchyma of BLM-treated lung (D) and focalized in fibrotic tissue (C). Bars: 1 mm.
Biocellvia’s assay compared to standard evaluation methods
A scientific collaboration between Biocellvia and Boehringer Ingelheim (Biberach, Germany) was established in regard to the validation of Biocellvia’s assay as an end-point measure of pulmonary fibrosis.
- Biocellvia’s assay has been compared with Ashcroft scoring, µCT analysis, Dynamic lung compliance and forced vital capacity in bleomycin mouse model.
- A significant correlation was found between Biocellvia’s assay and standard evaluation methods (figure 3).
Figure 3. Correlations between Biocellvia’s assay and Ashcroft scoring (A), µCT (B), Cdyn (C) and FVC (D) analyzes, before and after BLM administration at 0.25, 0.50, 0.75 and 1 mg/kg. Data correspond to mean value per animal (Control group: n = 6, BLM groups: n = 12/group). r = Spearman correlation coefficient. p-value < 0.05 was considered statistically significant.
Biocellvia’s assay, a high benefit/cost ratio
- Quantify accurately very low levels of pulmonary fibrosis.
> Use of low concentrations of bleomycin 4-5 times lower than those usually administered in rodents.
> Validation of the efficacy compounds on animals much less affected, eliminating totally the morbidity and contributing to a higher reliability of preclinical drug evaluation.
- A fully automated and observer-independent quantitative analysis performed on entire lung sections without any intra- and inter-variability.
- An accurate, reliable and time-saving (<2 sec/lung slice) histomorphological analysis.
Considering its unmatched benefits and its high correlation with conventional evaluation methods, Biocellvia’s IPF assay can be considered as a robust measurement of pulmonary fibrosis, giving access to a reliable preclinical drug evaluation, and consequently a crucial help to decision making.
The related results on pulmonary fibrosis gave rise to a scientific article in 2017 in PlosOne.