The findings of a new Weill Cornell Medicine study show that excessive iron buildup in the lungs may be a major cause of COPD. According to a Weill Cornell news release, the researchers also believe they have identified a gene that may cause the excess buildup, which is a gene previously found to increase a patient’s susceptibility to COPD.
For the study, the research team examined a gene that is tasked with regulating iron uptake in cells, called iron-responsive element-binding protein 2 (IRP2), and found that mice that express IRP2 developed the standard symptoms of COPD when exposed to cigarette smoke.
However, the results of them study revealed that rodents that lacked the gene remained healthy. A drug given to the symptomatic mice prevented additional lung damage and even reversed the effects of COPD.
Overall, the researchers exposed two sets of mice to cigarette smoke for 6 months, and the mice that lacked IRP2 were resistant to the effects of the smoke, and the rest developed first inflammation and then emphysema, which the researchers note are two common characteristics of COPD. The research team then examined the lung tissue of the mice and observed that mice expressing IRP2 had an excessive buildup of iron in their cells, especially in the mitochondria.
The Weill Cornell news release notes that this indicated that the presence of the IRP2 gene and its corresponding protein caused an increase in iron. Suzanne Cloonan, PhD, first author of the study, explains, “We think that this excess of mitochondrial iron leads to mitochondrial dysfunction. The mitochondria cannot behave as normal – they cannot utilize oxygen as well, they cannot make as much energy as they should, and they’re stressed out.”
The investigators say the discovery is significant because it validates the results of a 2009 study that implicated IRP2 in the disease’s development and demonstrate how the gene supports COPD, according to the Weill Cornell news release. In addition, the findings also illustrate IRP2 may be a potent therapeutic target.
Senior author of the study Augustine Choi, MD, says, “At the end of the day, we always like to have an impact on human disease, whether it’s improving diagnostics, prevention or therapeutics, and this study actually gets to the therapeutic angle. Not only does it validate our previous work, but it also provides us with a really good understanding of how IRP2 functions and facilitates the development of COPD.”
Choi adds, “The drugs we currently use for COPD really just relieve symptoms and don’t change the course of the disease. Our study suggests that we may be able to affect the progression of the disease. A cure would be even better.”
Source: Weill Cornell Medical College