Drug development for idiopathic pulmonary fibrosis (IPF) has been challenging due to poorly understood disease etiology, unpredictable disease progression, highly heterogeneous patient populations, and a lack of robust pharmacodynamic biomarkers. Moreover, because lung biopsy is invasive and dangerous, making the extent of fibrosis as a direct longitudinal measurement of IPF disease progression unfeasible, most clinical trials studying IPF can only assess progression of fibrosis indirectly through surrogate measures. This review discusses current state-of-art practices, identifies knowledge gaps, and brainstorms development opportunities for preclinical to clinical translation, clinical populations, pharmacodynamic endpoints, and dose optimization strategies. This article highlights clinical pharmacology perspectives in leveraging real-world data as well as modeling and simulation, special population considerations, and patient-centric approaches for designing future studies.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333628 | PMC |
http://dx.doi.org/10.1177/17534666231181537 | DOI Listing |
Sci Rep
January 2025
Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.
The traditional Chinese medicine compound preparation known as Jinbei Oral Liquid (JBOL) consists of 12 herbs, including Astragalus membranaceus (Fisch.) Bge, Codonopsis pilosula (Franch.) Nannf, et al.
View Article and Find Full Text PDFInt J Biochem Cell Biol
January 2025
Centre for Respiratory Research, Translational Medical Sciences, School of Medicine, University of Nottingham, UK; Nottingham NIHR Biomedical Research Centre, Nottingham, UK; Biodiscovery Institute, University Park, University of Nottingham, UK. Electronic address:
Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms.
View Article and Find Full Text PDFThorax
January 2025
Medicine, SUNY Downstate Medical Center, New York, New York, USA
Vascul Pharmacol
January 2025
Department of Internal Medicine, University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address:
Long non-coding RNA (lncRNA) may be involved in dysfunction of pulmonary artery endothelial cells (PAEC) and, thus, in pulmonary arterial hypertension (PAH) pathobiology. We screened the RNA expression profile of commercial human PAEC (hPAEC) exposed to increased hydrostatic pressure, and found that the lncRNA Down syndrome critical region 9 (DSCR9) was the most regulated transcript (log2FC 1.89 vs control).
View Article and Find Full Text PDFProteomes
January 2025
Research & Development, AbbVie Bioresearch Center, Worcester, MA 01605, USA.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis is identifying cell types associated with histopathological regions, particularly local fibrosis centers known as fibroblast foci. To address this, we integrated published spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) transcriptomics and adopted the Query method and the Overlap method to determine cell type enrichments in histopathological regions.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!