From Bench to Bedside:
New hope for patients with fibrosis of the lung and other organs
A diagnosis of idiopathic pulmonary fibrosis isn’t much better than a death sentence: there is no treatment and the survival rate is less than three years. There’s a gradual scarring of the lung, thickening and contracting the organ until it loses its ability to exchange oxygen with blood. Patients experience extreme fatigue, rapid weight loss, chronic cough and shortness of breath. The lung disease often affects older people and its cause is generally unknown – it’s possible that cumulative injuries like exposure to environmental toxins and pollutants in susceptible individuals could contribute.
Now Health System researchers have discovered that targeting a new gene was successful in treating pulmonary fibrosis in mice. Now they'll work on an approach for future testing in humans.
The treatments in mice attack an oxidant-generating enzyme, NOX4, that researchers discovered is involved in the fibrotic process — when scar-like tissue forms in an organ such as the lung.
“We’ve identified the target. We know the enemy now,” said Subramaniam Pennathur, M.D., assistant professor of internal medicine/nephrology. “This is the first study that shows pulmonary fibrosis is driven by this NOX4 enzyme. But what’s really significant is this discovery may have relevance to fibrosis in other organ systems, not just the lung.”
So those suffering from common cardiac or kidney diseases, which often involve fibrosis, may also benefit from treatments that result from this research.
Hope for Patients
The NOX4 discovery was made in the U-M lab of Victor J. Thannickal, M.D. He was assisted by Louise Hecker, Ph.D., a post-doctoral research fellow. Continued support from the National Institutes of Health will eventually allow researchers to take the treatment to human studies. U-M is seeking a patent on the treatment and the researchers’ findings are published in the September issue of the journal Nature Medicine.
Thannickal says the study points to a viable treatment strategy for idiopathic pulmonary fibrosis, and researchers saw success both in mouse models of lung fibrosis and in fibrogenic cells isolated from lungs of patients with idiopathic pulmonary fibrosis.
“It remains to be seen if fibrosis is reversible,” he said. “But therapeutic targeting of this pathway may allow us to halt the progression of fibrosis and preserve lung function.”
When U-M researchers induced the fibrotic process in the mice, they discovered that the NOX4 enzyme was elevated. By knocking down that enzyme at the genetic level or inhibiting its activity, the fibrosis was stopped.
“So we may be able to halt lung scarring even after the injury has occurred and fibrosis is set in motion,” Hecker says. “This research provides proof of concept that we can target this pathway for therapeutic benefit, which could potentially be used in humans.”
Both Hecker and Thannickal left U-M recently for the University of Alabama at Birmingham, but they plan to continue to work with Pennathur and other U-M researchers on anti-fibrotic therapies based on these studies. U-M has filed for patent protection and is currently looking for a licensing partner to help bring the technology to market.
Written by Mary Masson
"Having been diagnosed recently its refreshing to read something positive about ipf a disease that seems you only hear about once you have it.Great work good luck with your research its a cheering bit of news for those of us living under the prospect of an early and unpleasant demise." IA WestHead
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