Short Telomeres Cause of Deadly Lung Disease
The Johns Hopkins researchers who last year discovered a genetic cause of the inherited from of a deadly lung disease have now identified the same underlying cause in a majority of patients with the disease.
Telomeres, the protective ends on chromosomes that insure the integrity of genes, have been implicated by the group in a majority of cases of idiopathic pulmonary fibrosis (IPF). IPF causes a progressive and almost always lethal scarring of the lungs, and there is currently no effective therapy.
The research team studied telomeres in blood leukocytes and alveoli (the millions of air sacs in the lungs) of IPF patients with no family history and found that almost all of them had shortened telomeres when compared with healthy controls.
Their findings, published in the Sept. 2 issue of the Proceedings of the National Academy of Sciences, highlight that the disease, traditionally believed to be an immune-mediated disorder, may actually be due to short telomeres. Telomeres act as a clock mechanism in cells, and short telomeres can limit the life expectancy of certain cells within the lung. The team also uncovered evidence of a shortened-telomere syndrome in four patients who had both scarring in the liver and the lung. “Until now, we had no clues that explain the basic causes of IPF, and treatments have been hampered as a result,” says Mary Armanios, assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center and lead investigator of the study. “Strategies that targeted the immune system were unsuccessful. This research begins to explain why.”
Like the plastic end caps of shoe laces, telomeres extend just beyond the borders of needed genes, protecting the fragile ends of chromosomes. Shortened telomeres limit the body’s capacity to renew cells.
In 10 percent of hereditary cases of IPF, the team had found mutations in two genes that code for the enzyme telomerase, which helps maintain telomere length. In this study, patients with no family history also had short telomeres, emphasizing the relevance of the telomere pathway. It also highlights IPF as a potential manifestation of aging in the lung.
Armanios says these findings are a major advance in the understanding of this disease and should lead to new research on how to better treat it. “We are hoping to shift the paradigm,” she says. “We may now begin to think about using drugs that prevent telomere shortening and stop cells from dying.”
IPF affects 50,000 people each year. It occurs most often in those over age 60 and causes about 20,000 deaths annually. Lung transplant is currently the only treatment option. Average survival time for IPF patients is just three years.
In addition to Armanios, other research participants were Jonathan K. Alder, Julian J.-L. Chen, Lisa Lancaster, Sonye Danoff, Shu-chih Su, Joy D. Cogan, Irma Vulto, Mingyi Xie, Xiaodong Qi, Rubin M. Tuder, John A. Phillips III, Peter M. Landorp, and James E. Loyd,
The research was funded by the National Cancer Institute and Doris Duke Charitable Foundation.
Related Web site: www.coalitionforpf.org