Article

Molecular Source of Idiopathic Pulmonary Fibrosis Identified

Author(s):

Study show blocking FOXM1 can reduce the activation of fibroblasts as well as the process of idiopathic pulmonary fibrosis (IPF) itself.

In the recent study, Marc Peters-Golden, MD, a professor of internal medicine in the Division of Pulmonary and Critical Care Medicine at Michigan Medicine, research investigator L. Raghu Penke, PhD, and their study team proved (in principle) that blocking FOXM1 can reduce the activation of fibroblasts as well as the process of idiopathic pulmonary fibrosis (IPF) itself.

Results from the study, “FOXM1 is a critical driver of lung fibroblast activation and fibrogenesis,” were published by the Journal of Clinical Investigation.

"The role of FOXM1 within lung fibroblasts in pulmonary fibrosis had never before been investigated," Peters-Golden said. "We proved that, in principle, if we block FOXM1, we can reduce the activation of fibroblasts as well as the process of fibrosis itself."

IPF is characterized by tissue scarring in organs, primarily in the lungs. Diagnosed patients typically have a life expectancy of 3 to 5 years, with death most commonly occurring due to respiratory failure. Fibroblasts in patients with IPF have been shown to proliferate and expand in similar ways to cancer cells in a tumor.

Due to IPF’s overlapping similarities with cancer in relation to fibroblasts, Dr Peters-Golden and his team were led to FOXM1, which prior research has shown promotes cancer cell growth. By creating mice models, the team of researchers examined lung fibroblasts from patients with IPF and mice (whose fibrosis was triggered by a toxic drug). They found that both groups had increased levels of FOXM1.

Dr Peters-Golden explained the mechanisms of the study in a press release. "After we engineered the mice to eliminate the FOXM1 gene from the fibrotic fibroblasts, we administered the toxic drug that causes fibrosis and the result was the mice were substantially protected," he says. "This showed us that FOXM1 in fibroblasts was important for the process of fibrosis."

Upon sequentially giving the unaffected mice siomycin, which is an experimental compound designed to block FOXM1, the team observed that the drug prevented fibrosis in vivo.

"When we blocked FOXM1 with either the drug or the genetic approach, we reduced the accumulation of fibroblasts and decreased production of scar proteins, indicating to us that the excessive FOXM1 seemed to contribute to the bad behavior of the fibroblasts," stated Dr Peters-Golden.

While siomycin isn't approved for use in humans, work is being done to develop better drugs to block the overactivity of FOXM1 in cancer cells. If such drugs demonstrate safety in humans, they could be tested in clinical trials for IPF and possibly other scarring diseases of the lung, and different organs in the future.

In upcoming research, Dr Peters-Golden and his team intend to evaluate how inhibiting or deleting FOXM1 affects mice with a more advanced degree of fibrosis.

While the US Food and Drug Administration (FDA) approved the first drugs for IPF 3 years ago, all approved therapies only have the potential to slow disease progression; they don’t reverse the fibrosis that has already developed. Approved drugs include a variety of heart medications, some antibiotics, chemotherapy, and anti-inflammatory drugs.

"Although having some treatment options for IPF is no doubt an advance,” said Dr Peters-Golden, “in my view, these drugs are like a bunt single, rather than the home run we all want.”

To get the latest rare disease news sent directly to your inbox, subscribe to Rare Disease Report’s e-newsletter.

Related Videos
Developing Risk Assessment Tools for Viruses in School
Using Microbiomes to Diagnose Ventilator-Associated Pneumonia
What Do Patients Need to Learn About their Hypersensitivity Pneumonitis?
Discussing Use of Vaping Among Students, Conversations About Vaccines
Pavel Strnad, MD | Credit: RWTH Aachen
Janelle Bludhorn, MS, PA-C: How Common Medications Are Impacted by Extreme Heat
How to Screen for Heat-Related Illness Risks, with Janelle Bludhorn, MS, PA-C
A Promising Pipeline for COPD
Projecting Dupilumab's Fit in COPD
© 2024 MJH Life Sciences

All rights reserved.