image: Louise Hecker, PhD, far right, and members of her lab. view more
Credit: UAHS Biocommunications
TUCSON, Ariz. - 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.
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Dr. Hecker also recently received a $1 million grant from the U.S. Department of Veterans Affairs. The funds are helping her study another aspect of idiopathic pulmonary fibrosis: why the disease primarily arises in the elderly.
This work was supported by the Office of the Assistance Secretary of Defense for Health Affairs, through the Peer Reviewed Medical Research Program under award No. W81XWH-17-1-0443. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.
About the UA College of Medicine - Tucson
The University of Arizona College of Medicine - Tucson is shaping the future of medicine through state-of-the-art medical education programs, groundbreaking research and advancements in patient care in Arizona and beyond. Founded in 1967, the college boasts more than 50 years of innovation, ranking among the top medical schools in the nation for research and primary care. Through the university's partnership with Banner Health, one of the largest nonprofit health care systems in the country, the college is leading the way in academic medicine. For more information, visit medicine.arizona.edu
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