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Researchers Test Potential Drug Candidates for Deadly Lung Disease

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Scar tissue is a good thing. When you fall and scrape your knee, the natural process jumps into gear, sealing up wounds and healing damaged tissue.

But scar tissue can go haywire. Excessive scar tissue -- or fibrosis -- is the cause of many diseases that affect the internal organs; most have no cure.

Now, a $4.4 million grant from the U.S. Department of Defense will help researchers at the University of Arizona College of Medicine - Tucson focus on one particular fibrotic disease. Named idiopathic pulmonary fibrosis, the disease is caused by the formation of scar tissue within the lungs.

"It's basically a death sentence," said Louise Hecker, PhD, a UA associate professor of medicine who studies the disease and is the recipient of the new grant.

Patients typically survive just three years after diagnosis.

To improve this bleak outcome, Dr. Hecker's team will evaluate two potential drug candidates they believe can stop and even reverse excessive scar tissue growth in the lungs. The compounds will be studied to ensure they are safe, effective and potent in the method by which they are administered --¬ either orally or inhaled.

"Before we give these drug candidates to human patients in clinical trials, we have to perform rigorous, controlled testing to evaluate their safety and efficacy," Dr. Hecker explained.

The drug compounds will specifically target the enzyme Nox4. Past studies by Dr. Hecker have shown that Nox4 is significantly elevated in the lungs of patients with idiopathic pulmonary fibrosis, hinting that the overactive enzyme may be the cause of excessive scar tissue growth.

A separate study by Dr. Hecker showed that scar tissue formation can be reversed in mice with idiopathic pulmonary fibrosis if the enzyme Nox4 is blocked.

"Nox4 clearly plays a critical role in mediating scar tissue formation," Dr. Hecker said. "It is an important and exciting target for us to pursue for a cure."

Dr. Hecker's work has the potential to help patients who currently have no hope, said UA President Robert C. Robbins, MD.

"Idiopathic pulmonary fibrosis is a deadly disease with a very grim prognosis," he said. "Dr. Hecker has laid the groundwork for a potential cure that could save lives. I look forward to seeing what she discovers with the support from this grant."

The study will be supported by a team of expert scientists at UA Health Sciences, including medicinal chemist Vijay Gokhale, PhD, pharmacologist Heidi Mansour, PhD, and Brett Colson, PhD, who will study drug-target interactions. Phil Kuehl, PhD, a toxicologist at the Lovelace Respiratory Research Institute, also is a co-investigator.

Dr. Hecker said she is grateful to the UA BIO5 Institute for supporting her research. In 2016, BIO5 provided a $300,000 pilot grant for her research. The funds helped her identify the potential drug candidates for idiopathic pulmonary fibrosis, and with this DoD funding, she will now be able to continue their preclinical development.

This article has been republished from materials provided by the University of Arizona. Note: material may have been edited for length and content. For further information, please contact the cited source.