Steven Shapiro Delivers Lecture About Genomic Promise for COPD Therapies

Chronic obstructive pulmonary disease (COPD), which includes both emphysema and chronic bronchitis, is the fourth leading cause of death in the United States. Heart attack, cancer and stroke kill more people, but only COPD is becoming more prevalent. Sixteen million Americans have the disease, and there are 800 million victims globally. Strongly associated with cigarette smoking, COPD is expected to be the leading cause of death worldwide by 2010. So far, there is no cure. Doctors can only relieve symptoms.

According to Steven Shapiro, MD, the Parker B. Francis Professor of Medicine at Harvard Medical School and Chief of Pulmonary and Critical Care Medicine at the Brigham and Women’s Hospital, poor funding, the stigma that COPD is a self-induced disease, and the fact that it is hard to study low-level, long-term lung destruction in a laboratory have been obstacles to finding a cure for COPD. Today, however, he says that the stigma is lessening and funding is increasing because COPD is one of the top priorities of the National Heart, Lung, and Blood Institute (NHLBI).

Shapiro delivered the Thirteenth Harold and Marilyn Menkes Memorial Lecture at the Johns Hopkins Bloomberg School of Public Health on November 17.

“Dr. Shapiro is unique in that he is a clinician who is also at the forefront of molecular lab research in discovering genes that lead to the next generation of therapies for COPD,” said Shyam Biswal, assistant professor in the Department of Environmental Health Sciences.

Shapiro’s lecture, “Multidisciplinary Approach to COPD: Gene by Environment Interactions” described the work his laboratory has done to determine the molecular signaling of COPD. Ninety percent of COPD is due to cigarette smoking, but not everyone who smokes gets COPD. It is unclear why only 15 percent of smokers get COPD and the rest do not.

Shapiro cited the promise of genomics to help answer these questions. Studies in mice exposed to cigarette smoke have led to the discovery of genes that confer susceptibility to COPD.

By inducing emphysema in mice through cigarette smoking, his laboratory generated mice deficient in certain proteinases to determine their contribution to COPD. He found that MMP-12 and neutrophil elastase are necessary for emphysema to develop. He also studied other functions of these proteinases, and found that MMP-12 also can inhibit, rather than promote, tumor progression.

Other than the fact that “mice should not smoke cigarettes,” Shapiro said that his findings suggest that “inflammation/proteinase inhibition should stop the progression of emphysema.”

These findings could be used to develop pharmacogenetic therapies for the treatment of COPD. —Kristi Birch