Drug combo to hit root of asthma and bronchitis
The current treatments for asthma and chronic bronchitis only alleviate the symptoms, says a research.india Updated: Feb 03, 2006 12:48 IST
A new research has revealed that current treatments for asthma and chronic bronchitis do not address the ultimate source of the problem, in fact they can only alleviate the symptoms.
Researchers at Washington University School of Medicine in St. Louis have gone to the root of these disorders and found a two-drug treatment that could potentially restore patients' troubled airways to healthy function.
Michael J. Holtzman, M.D., and colleagues discovered that some cells that line the air passages of the lung transform into another cell type in mice and humans with these disorders. This cellular transformation had never before been recognized and is responsible for overproduction of mucus in the airways.
The researchers found that preventing the harmful transformation of lining cells could be accomplished with two drugs, and they assert that these drugs may possibly be used in combination to normalize the airway lining in asthma and chronic bronchitis sufferers.
"In these disorders, shortness of breath and cough are related to hypersecretion of mucus in the airway," says Holtzman, the Selma and Herman Seldin Professor of Medicine and director of pulmonary and critical care medicine.
"Physicians prescribe anti-inflammatory steroids and bronchodilators to ease breathing difficulties, but these medications don't specifically reduce mucus production or secretion. Our research addresses this aspect of the problem," he added.
The researchers were the first to demonstrate this transformation from ciliated to goblet cells in a model of chronic lung disease. They also demonstrated that a similar process may occur in humans with asthma and COPD, a disease classification that includes chronic bronchitis.
The first of these inhibitors is newly developed and is able to impede the activity of epidermal growth factor receptor (EGFR). EGFR was persistently overactive in the ciliated airway cells in mice with the asthma-like condition.
This chronic activity protected the ciliated cells from normally programmed cell death and allowed the cells to accumulate to higher than normal levels. By blocking EGFR, the inhibitor prevented the buildup of ciliated cells.
The second inhibitor the researchers tested interferes with signaling pathways activated by an immune-system protein known as interleukin-13 (IL-13). They found that IL-13 elicited the crucial change from ciliated to goblet cells in mouse airways and human airway cells in culture. Interfering with IL-13 prevented this transformation from one cell type to the other, a process known as transdifferentiation.
"Finding this sequence of events the increase in the level of ciliated cells and then the transdifferentiation of these cells to goblet cells opens up new treatment options that may be more effective than those tried in the past," Holtzman says.
"We've shown that if you combine the EGFR and IL-13 inhibitors in a rational way, you can restore the normal architecture of the airway lining. But you have to use the combination to fully correct the abnormalities."
First Published: Feb 03, 2006 12:48 IST