Hypertension Drug, Losartan, May Prevent Lung Damage Caused by Smoking
Losartan is a prescribed drug that mainly used for treating high blood pressure (hypertension). But recent study found that the prescribed hypertension drug may also be used to prevent lung damage caused by smoking.
In a study tested on mice, which has published in the Journal of Clinical Investigation, scientists at Johns Hopkins have proved that losartan is effective in the prevention of almost all lung damage caused from two months of exposure to cigarette smoke.
“The results show that losartan can serve as an effective treatment for smoking-related lung disease in humans. And because this drug is already approved for use in the United States as a safe and effective treatment for hypertension, incorporating it into our treatment regimen for COPD would be quite rapid, ” said Enid Neptune, MD, a pulmonologist and an associate professor at Johns Hopkins University School of Medicine, as reported in Epharmapedia.
As a result of the experiments, the trial will be continued in patients with smoking-related Chronic Obstructive Pulmonary Disease (COPD), the long-term consequence of smoking, and until now there are no potential treatment for this disease.
COPD is the third leading cause of death in the US, mostly in people with chronic bronchitis or emphysema. About 12 million Americans have been diagnosed with COPD.
In smoking-related COPD, breathing becomes difficult and progressively worsens. This condition happens because the small airways that allow oxygen pass through the lungs and into the bloodstream become damaged. Airway walls thicken and are more readily obstructed by mucus, and the airspaces lose their elasticity.
Previous research on losartan, by Dietz and other researchers, had demonstrated that the hypertension drug, part of a class of drugs called angiotensin II receptor antagonist, can block the action of a key signaling protein called transforming growth factor beta, or TGF-beta. Neptune’s own research showed that TGF-beta levels were elevated in lung tissue samples from smokers with COPD.
“Our research shows two distinct strategies to block TGF-beta signaling. This suggests that TGF-beta biological pathway may be a major contributor to the development of COPD disease,” said Neptune.
In the new set of experiments, the Johns Hopkins researchers first confirmed that elevated levels of TGF-beta in the lungs of mice exposed to cigarette smoke and in lung tissue samples from eight smokers with COPD. Biochemical analysis showed that smoke-exposed mice had a fourfold increase in TGF-beta signaling in their lung than mice exposed to indoor air only. TGF-beta signaling in the lungs of smokers with COPD was 25 percent greater than in smokers without COPD.
While continuing exposure to tobacco smoke, some mice were treated with either low dose of losartan (0.6 grams per liter), or a high dose (1.2 grams per liter). Another set of smoke-exposed mice was given a neutralizing antibody of TGF-beta signaling.
The researchers found improvements in more than a half-dozen measures of lung damage. The airway wall thickness was reduced by 50 percent in mice treated with either dose of losartan or with TGF-beta antibodies.
Losartan-treated mice showed no signs of lung over-expansion and no signs of increased collagen deposition, a gauge of TGF-beta activity, and had normal levels of elastin-metabolizing enzymes and protein fragments in the walls of their airbags. Measures oxidative stress, inflammation, and cell death were also better in mice that received losartan.
“It is very exciting that an existing medication has proven capable in an animal, not only disrupting the biological pathway that precipitated them, but also treating the COPD problems,” said Robert A. Wise, M.D., a pulmonologist and a professor at Johns Hopkins who is piloting the clinical studies. “If our tests in people prove successful, we could help restore lung health to millions of people who have suffered from tobacco addiction.”
Neptune and her team say their next steps are further experiments on the role of TGF-beta signaling in COPD and determining who best responds to anti-TGF-beta signaling treatments. This approach represents an early step toward personalized or individually specific treatments for COPD sufferers.