New Knowledge About Ofev and Esbriet May Lead to Better Lung Fibrosis Therapies
The new insights into these drugs work was gained by making use of a new cell model of lab-grown cells derived from patients.
“Currently, the drugs Nintedanib and Pirfenidone are widely used in treatment,” Claudia Staab-Weijnitz, senior author of the study and head of the research project at the Institute of Lung Biology and the Comprehensive Pneumology Center at Helmholtz Zentrum München, said in a news release.
She said both drugs slow the progression of the disease, but the mechanisms of action have not been are completely understood.
The team figured the drugs likely impact collagen synthesis and maturation. So to study these factors, they grew fibroblast cells from patients with both lung fibrosis and healthy controls. Fibroblasts are the cells that drive fibrosis development.
“We initially developed a cell culture system that is optimized for the study of collagen biosynthesis and maturation,” said Larissa Knüppel, the study’s first author.
Treating the cells with Ofev and Esbriet allowed the team to conclude that both drugs prevented the formation of new collagen molecules. Ofev had broader actions than Esbriet, reducing the gene activity of two types of collagen and the secretion of two other types. It also acted to reduce the gene activity of two fibrosis-associated molecular factors. Esbriet lowered one type of collagen, but showed fewer and less pronounced effects.
Both drugs, however, also prevented collagen from assembling into the larger fibrils that make up fibrotic tissue. The treatment resulted in fewer and thinner collagen fibrils compared to untreated patient-derived cells.
This discovery of how the drugs work to slow disease progression may aid researchers in their efforts to develop even better treatments for pulmonary fibrosis.
“The results show that the optimized human system allows the study of collagen biosynthesis and collagen fibril formation at all regulatory levels. Thus, it is very well suited for use as an initial test system for novel therapeutic strategies for lung fibrosis,” Staab-Weijnitz said.