Drug Shields Mice From Emphysema
MONDAY Dec. 22, 2008 -- In experiments in mice, scientists have shown that a new drug may protect the animals from the respiratory damage caused by cigarettes.
The finding holds out hope for patients with chronic obstructive pulmonary disease (COPD) -- a chronic progressive lung disease involving both emphysema and chronic obstructive bronchitis.
COPD, most commonly linked to smoking, is the fourth leading cause of death in the United States and there are no effective treatments.
"Our previous studies have shown that there is a defect in Nrf2 -- a master regulator of antioxidant and detoxifying pathways -- in the lungs of COPD patients that may be involved in the severity of this disease," explained lead researcher Shyam Biswal, an associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.
In this study, the researchers used a novel drug molecule called CDDO-imidazole (CDDO-Im) to curb the progression of the disease by targeting the Nrf2 pathway.
"The result demonstrates that this strategy is effective in the preclinical model of emphysema," Biswal said.
The report is published in this week's online edition of the Proceedings of the National Academy of Sciences.
For the study, Biswal's team exposed mice to cigarette smoke for six months. Half the mice were treated with CDDO-Im while the other animals were not.
The researchers found that mice treated with CDDO-Im did not develop heart and lung damage while their untreated counterparts did.
Dr. Norman Edelman, chief medical officer of the American Lung Association, believes the new approach to treating COPD could be effective.
"There have been several studies identifying disrupted oxidant defense systems in COPD," Edelman said. "What's different about this one is that a control point for a whole group of oxidant defenses has been identified in rather elegant studies. Thus, if a therapy up-regulating this site were developed it would be more likely to be effective in COPD," he said.
This study provides hope that strategies aimed at targeting the Nrf2 pathway might be effective in inhibiting the development of emphysema, Biswal said.
"Future studies will be done in COPD patients to test the strategy of targeting Nrf2, to test the efficacy in reducing the burden of this debilitating disease," Biswal said.
However, Dr. Bartolome R. Celli, chief of pulmonary care at St. Elizabeth's Medical Center in Boston, said the jury is still out on the effectiveness of this approach.
"It is an interesting and intriguing study," Celli said. "However, from the experiments in mice to reality in humans there usually is a great distance," he said.
There is consensus that oxidative stress associated with cigarette smoking is important in COPD, so balancing oxidative stress with antioxidants makes sense, Celli said.
"This study takes it one step further by testing the hypothesis in vivo [animals]," according to Celli. "Let's wait for the translation into humans," he said.
For more information on emphysema, visit the U.S. National Library of Medicine .
Posted: December 2008
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