Novel NOX4 Blockers Could Treat Fibrosis at the Source, Scientists Say

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by José Lopes, PhD |

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Novel selective blockers of the NOX4 enzyme could ease oxidative stress and the subsequent development of fibrosis in lungs and other organs, according to scientists at the University of Arizona.

The potential treatments have been licensed to a startup called Fibronox to speed up their development.

NOX4, or NADPH oxidase 4, is a source of reactive oxygen species (ROS) — free radicals that may damage DNA, lipids (fat), and proteins. If ROS production outweighs the body’s antioxidant defenses, it induces oxidative stress, which has been linked to the development of fibrosis (scarring) in lungs and other organs, as well as neurodegenerative diseases, depression, and cancer.

Louise Hecker, PhD, and her team at The University of Arizona (UA) College of Medicine – Tucson and the BIO5 Institute were the first to discover NOX4 as a central driver of pulmonary fibrosis. The researchers showed that idiopathic pulmonary fibrosis (IPF) patients have significantly higher levels of NOX4 in their lungs.

Hecker’s team received a $4.4-million grant from the U.S. Department of Defense in 2018 to study two experimental treatments that target NOX4, as a way to ease fibrosis. This hypothesis was supported by preclinical work which showed a reversal of fibrosis when NOX4 was blocked. Previously, Hecker had also received a $300,000 pilot grant from the BIO5 Institute, and a $1-million grant from the U.S. Department of Veterans Affairs, to discover why IPF disproportionately affects the elderly.

“Fibrotic disease impacts millions of healthcare consumers,” Hecker said in a UA news release, written by Paul Tumarkin.

Hecker noted that the many failed clinical trials on treatments for fibrotic disorders indicates a clear need for improved therapies, and that having a compound targeting Nox4 “would shut down oxidant production to combat oxidative stress and stop the problem at the source.”

Through its Tech Launch Arizona (TLA), the UA has already licensed the technology to Fibronox, a startup company founded by Hecker.

“We are excited to see Fibronox taking the next steps to develop this invention,” Doug Hockstad, TLA’s assistant vice president, said. “We look forward to seeing the company and the technology improve the lives of those suffering from fibrosis.”

The Fibronox team participated in TLA’s National Science Foundation I-Corps program, which is intended to extend research focus beyond the laboratory, and quicken product development towards commercialization. Fibronox was also invited to represent UA at the San Diego Innovation Showcase in October.

The company will be one of 12 national finalists to present at Science2Startup on April 23 in Cambridge, Massachusetts. This invitation-only symposium brings together top research institutions and biotech investors.

“Louise and the Fibronox team have put the hard work in to get this company started on the right path to success,” Joann MacMaster, TLA’s senior director of venture development, said. “This team is strong and ready to take this project forward.”

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