August 24, 2009

BIRMINGHAM, Ala. - Researchers now at the University of Alabama at Birmingham (UAB) have identified an oxidant-generating enzyme, NOX 4, as a key element in the development of fibrosis, or scarring, in the lungs and other organs. In findings to be published online this month in Nature Medicine, the research team successfully treated mice with injury-induced pulmonary fibrosis using genetic and pharmacologic strategies aimed at NOX4.

The researchers, working then at the University of Michigan, discovered after inducing pulmonary fibrosis in mice that levels of NOX4 were elevated.  Fibrosis was halted when the team was able to inhibit NOX 4 and restrict its activity.

"This study points to a very viable treatment strategy for idiopathic pulmonary fibrosis," said Victor Thannickal, M.D., professor and director of the Division of Pulmonary, Allergy and Critical Care Medicine at UAB. "It remains to be seen if fibrosis is reversible, but therapeutic targeting of this pathway may allow us to halt the progression of fibrosis and preserve lung function."

The research was done in Thannickal's Michigan laboratory before he joined the UAB faculty in July. He and Louise Hecker, Ph.D., the study's first author who also has joined the UAB faculty, plan to develop inhibitors of NOX4 for future studies in human patients. Currently there is no treatment for pulmonary fibrosis, and survival is usually less than three years.

Idiopathic pulmonary fibrosis often affects older people, Thannickal said. While the exact cause is unknown, exposure over time to environmental toxins and pollutants in genetically susceptible individuals is thought to be at least partially responsible for fibrosis. There are more than 500,000 patients with pulmonary fibrosis in the United States and an estimated 5 million worldwide, according to the Pulmonary Fibrosis Foundation.

Thannickal says that the NOX4 pathway may also be relevant to the treatment of fibrosis in other organs. Fibrosis is common in the kidney and cardiovascular system, and future research targeting NOX4 may unlock therapies for other disease indications.

About the Division of Pulmonary, Allergy and Critical Care

The nationally recognized UAB Division of Pulmonary, Allergy and Critical Care Medicine provides a variety of comprehensive clinical treatments for respiratory, pulmonary vascular and allergic disorders. The division's many clinical research programs participate in research networks, such as the National Institutes of Health-funded COPD and Pulmonary Fibrosis Networks, the American Lung Association Asthma Clinical Research Network and the Cystic Fibrosis Foundation Therapeutics Development Network.