Drug shields mice from chronic lung disease: study

By Julie Steenhuysen

CHICAGO (Reuters) - An experimental drug protected mice exposed to tobacco smoke from developing chronic lung disease, raising hope for a treatment in humans, U.S. researchers said on Monday.

They said the chemical CDDO-Im helped activate a master gene called Nrf2 that bolsters the lung's ability to fight off chronic obstructive pulmonary disease, or COPD, a condition that includes emphysema, chronic bronchitis and some types of serious chronic asthma.

"COPD is the 4th-largest killer in the world with no effective drugs," Shyam Biswal of Johns Hopkins School of Medicine in Maryland, who worked on the study, said in an e-mail.

In prior research, Biswal and colleagues found that Nrf2 works as a "master gene," turning on genes involved in protecting the lungs from pollution and cigarette smoke.

"The Nrf2 pathway is the major antioxidant and detoxifying response in the lungs. Therapies targeting this pathway need to be developed and tested in patients," said Biswal, whose study was published in the Proceedings of the National Academy of Sciences.

For the study in mice, Biswal and colleagues studied the drug compound CDDO-Im, which induces the Nrf2 gene to activate a host of antioxidant genes. "This antioxidant response detoxifies the harmful molecules that cause lung damage," he said.

The researchers exposed mice to cigarette smoke for six months to simulate the lung damage seen in emphysema.

Mice that received the drug were protected against lung damage and also showed dramatically improved heart function compared to the untreated mice.

Privately held Reata Pharmaceuticals Inc of Irving, Texas, is studying a drug in the same class, CDDO-Me, as a potential treatment for cancer under the name RTA-402.

"Both compounds are potent Nrf2 activators. Since CDDO-Me is going through clinical trial for lung cancer, it may be used for a future clinical trial for COPD," Biswal said.

COPD affects 210 million people worldwide. Smoking is by far the leading cause, but environmental factors such as pollution also play a role.